Nausea and Vomiting–for health professionals (PDQ®)

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Overview

Prevention and control of nausea and vomiting (emesis) (N&V) are paramount in the treatment of cancer patients. Chemotherapy-induced N&V (CINV) is one of the most distressing acute side effects of cancer treatment; it occurs in up to 80% of patients and can have a significant impact on a patient’s quality of life. N&V can also result in the following:

  • Serious metabolic derangements.
  • Nutritional depletion and anorexia.
  • Deterioration of patients’ physical and mental status.
  • Esophageal tears.
  • Fractures.
  • Wound dehiscence.
  • Withdrawal from potentially useful and curative antineoplastic treatment.
  • Degeneration of self-care and functional ability.

Health Care Costs

Severe N&V may result in prolonged hospitalizations, inability to continue usual activities, need for additional support, and depression, producing greater effects on health care costs. One review of 12 published studies [1] found that despite the high costs associated with prophylaxis against CINV, the direct cost of care was higher for patients who did not receive adequate CINV prophylaxis. Indirect costs related to lost work hours were also higher for patients with uncontrolled CINV. Another study examined 178 patients receiving highly or moderately emetogenic chemotherapy for their first chemotherapy course.[2] Despite prophylaxis, 61% still experienced CINV. Higher direct and indirect health care costs and lower Functional Living Index—Emesis (FLIE) scores for quality of life were seen in patients who failed prophylaxis. One group of investigators looked at the Premier Perspective database to study 19,139 patients, all of whom received prophylaxis. In those with uncontrolled CINV, the overall mean additional costs were $5,299 per episode.[3]

In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.

References
  1. Carlotto A, Hogsett VL, Maiorini EM, et al.: The economic burden of toxicities associated with cancer treatment: review of the literature and analysis of nausea and vomiting, diarrhoea, oral mucositis and fatigue. Pharmacoeconomics 31 (9): 753-66, 2013. [PUBMED Abstract]
  2. Haiderali A, Menditto L, Good M, et al.: Impact on daily functioning and indirect/direct costs associated with chemotherapy-induced nausea and vomiting (CINV) in a U.S. population. Support Care Cancer 19 (6): 843-51, 2011. [PUBMED Abstract]
  3. Burke TA, Wisniewski T, Ernst FR: Resource utilization and costs associated with chemotherapy-induced nausea and vomiting (CINV) following highly or moderately emetogenic chemotherapy administered in the US outpatient hospital setting. Support Care Cancer 19 (1): 131-40, 2011. [PUBMED Abstract]

Pathophysiology

Nausea is the subjective phenomenon of an unpleasant, wavelike sensation experienced in the back of the throat and/or the epigastrium that may culminate in vomiting (emesis). Vomiting is the forceful expulsion of the contents of the stomach, duodenum, or jejunum through the oral cavity. Retching involves the gastric and esophageal movements of vomiting without expulsion of vomitus and is also referred to as dry heaves.

Progress has been made in understanding the neurophysiologic mechanisms that control nausea and vomiting (N&V). Both are controlled or mediated by the central nervous system but by different mechanisms. Nausea is mediated through the autonomic nervous system. Vomiting results from the stimulation of a complex reflex that includes a convergence of afferent stimulation from the following:[1,2]

  • A chemoreceptor trigger zone (CTZ, area postrema).
  • The cerebral cortex and the limbic system in response to sensory stimulation (particularly smell and taste), psychological distress, and pain.
  • The vestibular-labyrinthine apparatus of the inner ear in response to body motion.
  • Peripheral stimuli from visceral organs and vasculature (via vagal and spinal sympathetic nerves) as a result of exogenous chemicals and endogenous substances that accumulate during inflammation, ischemia, and irritation.

Neurotransmitters (including serotonin, substance P, and dopamine found in the CTZ), the vomiting center (thought to be located in the nucleus tractus solitarius), and enterochromaffin cells in the gastrointestinal tract then release efferent impulses that are transmitted to the abdominal musculature, salivation center, and respiratory center. The relative contribution from these multiple pathways culminating in N&V symptoms is complex and is postulated to account for the variable emetogenicity (intrinsic emetogenicity and mitigating factors [i.e., dosage, administration route, and exposure duration]) and emetogenic profile (i.e., time to onset, symptom severity, and duration) of agents.[3,4]

References
  1. Wickham R: Evolving treatment paradigms for chemotherapy-induced nausea and vomiting. Cancer Control 19 (2 Suppl): 3-9, 2012. [PUBMED Abstract]
  2. Navari RM: Antiemetic control: toward a new standard of care for emetogenic chemotherapy. Expert Opin Pharmacother 10 (4): 629-44, 2009. [PUBMED Abstract]
  3. Cefalo MG, Ruggiero A, Maurizi P, et al.: Pharmacological management of chemotherapy-induced nausea and vomiting in children with cancer. J Chemother 21 (6): 605-10, 2009. [PUBMED Abstract]
  4. Darmani NA, Crim JL, Janoyan JJ, et al.: A re-evaluation of the neurotransmitter basis of chemotherapy-induced immediate and delayed vomiting: evidence from the least shrew. Brain Res 1248: 40-58, 2009. [PUBMED Abstract]

General Risk Factors and Etiologies

Although most patients receiving chemotherapy are at risk for nausea and vomiting (emesis) (N&V), the onset, severity, triggers, and duration vary. Tumor-related, treatment-related, and patient-related factors all contribute, including tumor location, chemotherapy agents used, and radiation exposure.[1-3]

Patient-related factors may include the following:

  • Incidence and severity of N&V during past courses of chemotherapy. Patients with poor control of N&V during past chemotherapy cycles are likely to experience N&V in subsequent cycles.
  • History of chronic alcohol use. Cisplatin-induced N&V is less likely to occur in patients with a history of chronic high intake of alcohol.[4]
  • Age. N&V is more likely to occur in patients younger than 50 years.[5]
  • Gender. N&V is more likely to occur in women.[5,6]
  • History of motion sickness or emesis during pregnancy.

Additional causal factors unrelated to the chemotherapy treatment may include the following:

  • Fluid and electrolyte imbalances such as hypercalcemia, volume depletion, or water intoxication.
  • Tumor invasion or growth in the gastrointestinal tract, liver, or central nervous system, especially the posterior fossa.
  • Constipation.
  • Certain drugs such as opioids.
  • Infection or septicemia.
  • Uremia.

Clinicians treating N&V must be alert to all potential causes and factors, especially in cancer patients who may be receiving combinations of several treatments and medications. (Refer to the PDQ summary on Pain for more information about opioid-induced N&V.)

Classifications

N&V has been classified as acute, delayed, anticipatory, breakthrough, refractory, and chronic, as outlined below:[7-9]

  • Acute N&V: N&V experienced during the first 24 hours after chemotherapy administration is considered acute N&V.[10]
  • Delayed (or late) N&V: N&V that occurs more than 24 hours after chemotherapy administration is considered delayed, or late, N&V. Delayed N&V is associated with cisplatin, cyclophosphamide, and other drugs (e.g., doxorubicin and ifosfamide) given at high doses or on 2 or more consecutive days.
  • Anticipatory N&V (ANV): ANV is nausea and/or vomiting that occurs before a new cycle of chemotherapy is begun, in response to conditioned stimuli such as the smells, sights, and sounds of the treatment room. ANV is a classically conditioned response that typically occurs after three or four chemotherapy treatments after which the patient experienced acute or delayed N&V.
  • Breakthrough N&V: Vomiting that occurs within 5 days of prophylactic use of antiemetics and requires rescue is termed breakthrough N&V.
  • Refractory N&V: N&V that does not respond to treatment.
  • Chronic N&V in advanced-cancer patients: Chronic N&V in patients with advanced cancer is N&V associated with a variety of potential etiologies. A definitive understanding of cause is neither well known nor well researched, but potential causal factors include gastrointestinal, cranial, metabolic, drug-induced (e.g., morphine), cytotoxic chemotherapy–induced, and radiation-induced mechanisms.[11]
Table 1. National Cancer Institute’s Common Terminology Criteria for Adverse Events: N&Va
Adverse Event Grade Description
N&V = nausea and vomiting (emesis); TPN = total parenteral nutrition.
aAdapted from National Cancer Institute.[12]
bDefinition: A disorder characterized by a queasy sensation and/or the urge to vomit.
cDefinition: A disorder characterized by the reflexive act of ejecting the contents of the stomach through the mouth.
Nauseab 1 Loss of appetite without alteration in eating habits
2 Oral intake decreased without significant weight loss, dehydration, or malnutrition
3 Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated
4 Grade not assigned
5 Grade not assigned
Vomitingc 1 1–2 episodes (separated by 5 min) in 24 h
2 3–5 episodes (separated by 5 min) in 24 h
3 ≥6 episodes (separated by 5 min) in 24 h; tube feeding, TPN, or hospitalization indicated
4 Life-threatening consequences; urgent intervention indicated
5 Death
References
  1. Farrell C, Brearley SG, Pilling M, et al.: The impact of chemotherapy-related nausea on patients' nutritional status, psychological distress and quality of life. Support Care Cancer 21 (1): 59-66, 2013. [PUBMED Abstract]
  2. Dranitsaris G, Bouganim N, Milano C, et al.: Prospective validation of a prediction tool for identifying patients at high risk for chemotherapy-induced nausea and vomiting. J Support Oncol 11 (1): 14-21, 2013. [PUBMED Abstract]
  3. Bouganim N, Dranitsaris G, Hopkins S, et al.: Prospective validation of risk prediction indexes for acute and delayed chemotherapy-induced nausea and vomiting. Curr Oncol 19 (6): e414-21, 2012. [PUBMED Abstract]
  4. Sullivan JR, Leyden MJ, Bell R: Decreased cisplatin-induced nausea and vomiting with chronic alcohol ingestion. N Engl J Med 309 (13): 796, 1983. [PUBMED Abstract]
  5. Tonato M, Roila F, Del Favero A: Methodology of antiemetic trials: a review. Ann Oncol 2 (2): 107-14, 1991. [PUBMED Abstract]
  6. Roila F, Tonato M, Basurto C, et al.: Antiemetic activity of high doses of metoclopramide combined with methylprednisolone versus metoclopramide alone in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research. J Clin Oncol 5 (1): 141-9, 1987. [PUBMED Abstract]
  7. Kris MG, Urba SG, Schwartzberg LS: Clinical roundtable monograph. Treatment of chemotherapy-induced nausea and vomiting: a post-MASCC 2010 discussion. Clin Adv Hematol Oncol 9 (1): suppl 1-15, 2011. [PUBMED Abstract]
  8. Hesketh PJ: Chemotherapy-induced nausea and vomiting. N Engl J Med 358 (23): 2482-94, 2008. [PUBMED Abstract]
  9. Grunberg SM, Osoba D, Hesketh PJ, et al.: Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--an update. Support Care Cancer 13 (2): 80-4, 2005. [PUBMED Abstract]
  10. Wickham R: Nausea and vomiting. In: Yarbo CH, Frogge MH, Goodman M, eds.: Cancer Symptom Management. 2nd ed. Sudbury, Mass: Jones and Bartlett Publishers, 1999, pp 228-263.
  11. Schwartzberg L: Chemotherapy-induced nausea and vomiting: state of the art in 2006. J Support Oncol 4 (2 Suppl 1): 3-8, 2006. [PUBMED Abstract]
  12. National Cancer Institute: Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. Bethesda, Md: U.S. Department of Health and Human Services, National Institutes of Health, 2010. Available online. Last accessed June 25, 2015.

Anticipatory Nausea and Vomiting (Emesis)

Prevalence

The prevalence of anticipatory nausea and vomiting (emesis) (ANV) has varied, owing to changing definitions and assessment methods.[1] However, anticipatory nausea appears to occur in approximately 29% of patients receiving chemotherapy (about one of three patients), while anticipatory vomiting appears to occur in 11% of patients (about one of ten patients).[2] With the introduction of new pharmacologic agents (5-hydroxytryptamine-3 or 5-HT3 receptor antagonists), it was anticipated that the prevalence of ANV might decline; however, studies have shown mixed results. One study found a lower incidence of ANV,[3] and three studies found comparable incidence rates.[2,4,5] It appears that the 5-HT3 agents reduce postchemotherapy vomiting but not postchemotherapy nausea,[2,5] and the resulting impact on ANV is unclear.

Classical Conditioning

Although other theoretical mechanisms have been proposed,[6] ANV appears to be best explained by classical conditioning (also known as Pavlovian or respondent conditioning).[7] In classical conditioning, a previously neutral stimulus (e.g., smells of the chemotherapy environment) elicits a conditioned response (e.g., ANV) after a number of pairings or learning trials. In cancer chemotherapy, the first few chemotherapy infusions are the learning trials. The chemotherapy drugs are the unconditioned stimuli that elicit postchemotherapy N&V (in some patients). The drugs are paired with a variety of other neutral, environmental stimuli (e.g., smells of the setting, presence of the oncology nurse, chemotherapy room). These previously neutral stimuli then become conditioned stimuli and elicit ANV in future chemotherapy cycles. ANV is not an indication of psychopathology but is rather a learned response that, in other life situations (e.g., food poisoning), results in adaptive avoidance.

A variety of correlational studies provide empirical support for classical conditioning. For example, the prevalence of ANV before treatment with any chemotherapy is very rare, and few patients ever experience ANV without previous postchemotherapy nausea.[8] Also, most studies have found (1) a higher probability of ANV with increasing numbers of chemotherapy infusions, and (2) the intensity of ANV increasing as patients get closer to the actual time of their infusion.[9] In one experimental study, it was shown that a novel beverage could become a conditioned stimulus to nausea when paired with several chemotherapy treatments.[10]

Variables Correlated with ANV

Many variables have been investigated as potential factors that correlate with the incidence of ANV in hopes of developing a list of risk factors. There is currently no agreement on which factors predict ANV. A patient with fewer than three of the first eight characteristics listed below, however, is unlikely to develop ANV, and screening after the first chemotherapy infusion could identify patients at increased risk.[11]

Variables Found to Correlate With ANV

  1. Age younger than 50 years.
  2. N&V after last chemotherapy session.
  3. Posttreatment nausea described as moderate, severe, or intolerable.
  4. Posttreatment vomiting described as moderate, severe, or intolerable.
  5. Feeling warm or hot all over after last chemotherapy session.
  6. Susceptibility to motion sickness.
  7. Female gender.
  8. High-state anxiety (anxiety reactive to specific situations).[12,13]
  9. Greater reactivity of the autonomic nervous system and slower reaction time.[14]
  10. Patient expectations of chemotherapy-related nausea before beginning treatment.[15,16]
  11. Percentage of infusions of chemotherapy followed by nausea.[17]
  12. Postchemotherapy dizziness.
  13. Longer latency of onset of posttreatment N&V.[18]
  14. Emetogenic potential of various chemotherapeutic agents. Patients receiving drugs with a moderate to severe potential for posttreatment N&V are more likely to develop ANV.[12]
  15. History of morning sickness during pregnancy.

Treatment of ANV

Antiemetic drugs do not seem to control ANV once it has developed;[2] however, a variety of behavioral interventions have been investigated.[19] These include the following:

  • Progressive muscle relaxation with guided imagery.[20]
  • Hypnosis.[21]
  • Systematic desensitization.[22]
  • Electromyography and thermal biofeedback.[23]
  • Distraction via the use of video games.[24,25]

Progressive muscle relaxation with guided imagery, hypnosis, and systematic desensitization has been studied the most and is the recommended treatment. Referral to a psychologist or other mental health professional with specific training and experience in working with cancer patients is recommended when ANV is identified. The earlier ANV is identified, the more likely treatment will be effective; thus, early screening and referral are essential. However, physicians and nurses underestimate the incidence of chemotherapy-induced N&V.[26][Level of evidence: II]

Clearly, the most important aspect of ANV is prevention of acute and delayed N&V associated with chemotherapy. Most antiemetics have not shown benefit for the treatment of ANV, but the use of antiemetics during chemotherapy may have a dramatic effect in decreasing the incidence of ANV. The only class of medication that has shown benefit in some studies is benzodiazepines, most commonly lorazepam.[27][Level of evidence: IV]

References
  1. Andrykowski MA: Defining anticipatory nausea and vomiting: differences among cancer chemotherapy patients who report pretreatment nausea. J Behav Med 11 (1): 59-69, 1988. [PUBMED Abstract]
  2. Morrow GR, Roscoe JA, Kirshner JJ, et al.: Anticipatory nausea and vomiting in the era of 5-HT3 antiemetics. Support Care Cancer 6 (3): 244-7, 1998. [PUBMED Abstract]
  3. Aapro MS, Kirchner V, Terrey JP: The incidence of anticipatory nausea and vomiting after repeat cycle chemotherapy: the effect of granisetron. Br J Cancer 69 (5): 957-60, 1994. [PUBMED Abstract]
  4. Fernández-Marcos A, Martín M, Sanchez JJ, et al.: Acute and anticipatory emesis in breast cancer patients. Support Care Cancer 4 (5): 370-7, 1996. [PUBMED Abstract]
  5. Roscoe JA, Morrow GR, Hickok JT, et al.: Nausea and vomiting remain a significant clinical problem: trends over time in controlling chemotherapy-induced nausea and vomiting in 1413 patients treated in community clinical practices. J Pain Symptom Manage 20 (2): 113-21, 2000. [PUBMED Abstract]
  6. Reesal RT, Bajramovic H, Mai F: Anticipatory nausea and vomiting: a form of chemotherapy phobia? Can J Psychiatry 35 (1): 80-2, 1990. [PUBMED Abstract]
  7. Stockhorst U, Klosterhalfen S, Steingruber HJ: Conditioned nausea and further side-effects in cancer chemotherapy: a review. Journal of Psychophysiology 12 (suppl 1): 14-33, 1998.
  8. Morrow GR, Rosenthal SN: Models, mechanisms and management of anticipatory nausea and emesis. Oncology 53 (Suppl 1): 4-7, 1996. [PUBMED Abstract]
  9. Montgomery GH, Bovbjerg DH: The development of anticipatory nausea in patients receiving adjuvant chemotherapy for breast cancer. Physiol Behav 61 (5): 737-41, 1997. [PUBMED Abstract]
  10. Bovbjerg DH, Redd WH, Jacobsen PB, et al.: An experimental analysis of classically conditioned nausea during cancer chemotherapy. Psychosom Med 54 (6): 623-37, 1992 Nov-Dec. [PUBMED Abstract]
  11. Morrow GR, Roscoe JA, Hickok JT: Nausea and vomiting. In: Holland JC, Breitbart W, Jacobsen PB, et al., eds.: Psycho-oncology. New York, NY: Oxford University Press, 1998, pp 476-484.
  12. Andrykowski MA, Redd WH, Hatfield AK: Development of anticipatory nausea: a prospective analysis. J Consult Clin Psychol 53 (4): 447-54, 1985. [PUBMED Abstract]
  13. Roscoe JA, Morrow GR, Hickok JT, et al.: Biobehavioral factors in chemotherapy-induced nausea and vomiting. J Natl Compr Canc Netw 2 (5): 501-8, 2004. [PUBMED Abstract]
  14. Kvale G, Psychol C, Hugdahl K: Cardiovascular conditioning and anticipatory nausea and vomiting in cancer patients. Behav Med 20 (2): 78-83, 1994 Summer. [PUBMED Abstract]
  15. Montgomery GH, Tomoyasu N, Bovbjerg DH, et al.: Patients' pretreatment expectations of chemotherapy-related nausea are an independent predictor of anticipatory nausea. Ann Behav Med 20 (2): 104-9, 1998 Spring. [PUBMED Abstract]
  16. Shelke AR, Roscoe JA, Morrow GR, et al.: Effect of a nausea expectancy manipulation on chemotherapy-induced nausea: a university of Rochester cancer center community clinical oncology program study. J Pain Symptom Manage 35 (4): 381-7, 2008. [PUBMED Abstract]
  17. Tomoyasu N, Bovbjerg DH, Jacobsen PB: Conditioned reactions to cancer chemotherapy: percent reinforcement predicts anticipatory nausea. Physiol Behav 59 (2): 273-6, 1996. [PUBMED Abstract]
  18. Chin SB, Kucuk O, Peterson R, et al.: Variables contributing to anticipatory nausea and vomiting in cancer chemotherapy. Am J Clin Oncol 15 (3): 262-7, 1992. [PUBMED Abstract]
  19. Carey MP, Burish TG: Etiology and treatment of the psychological side effects associated with cancer chemotherapy: a critical review and discussion. Psychol Bull 104 (3): 307-25, 1988. [PUBMED Abstract]
  20. Lyles JN, Burish TG, Krozely MG, et al.: Efficacy of relaxation training and guided imagery in reducing the aversiveness of cancer chemotherapy. J Consult Clin Psychol 50 (4): 509-24, 1982. [PUBMED Abstract]
  21. Redd WH, Andresen GV, Minagawa RY: Hypnotic control of anticipatory emesis in patients receiving cancer chemotherapy. J Consult Clin Psychol 50 (1): 14-9, 1982. [PUBMED Abstract]
  22. Morrow GR, Morrell C: Behavioral treatment for the anticipatory nausea and vomiting induced by cancer chemotherapy. N Engl J Med 307 (24): 1476-80, 1982. [PUBMED Abstract]
  23. Burish TG, Shartner CD, Lyles JN: Effectiveness of multiple muscle-site EMG biofeedback and relaxation training in reducing the aversiveness of cancer chemotherapy. Biofeedback Self Regul 6 (4): 523-35, 1981. [PUBMED Abstract]
  24. Kolko DJ, Rickard-Figueroa JL: Effects of video games on the adverse corollaries of chemotherapy in pediatric oncology patients: a single-case analysis. J Consult Clin Psychol 53 (2): 223-8, 1985. [PUBMED Abstract]
  25. Vasterling J, Jenkins RA, Tope DM, et al.: Cognitive distraction and relaxation training for the control of side effects due to cancer chemotherapy. J Behav Med 16 (1): 65-80, 1993. [PUBMED Abstract]
  26. Chan CW, Cheng KK, Lam LW, et al.: Psycho-educational intervention for chemotherapy-associated nausea and vomiting in paediatric oncology patients: a pilot study. Hong Kong Med J 14 (5 Suppl): 32-5, 2008. [PUBMED Abstract]
  27. Rock EM, Limebeer CL, Parker LA: Anticipatory nausea in animal models: a review of potential novel therapeutic treatments. Exp Brain Res 232 (8): 2511-34, 2014. [PUBMED Abstract]

Acute or Delayed Chemotherapy-Induced Nausea and Vomiting (Emesis) Etiology

Acute Nausea and Vomiting (N&V)

The incidence of acute N&V with moderate- or high-risk chemotherapy ranges from 30% to 90%.[1-3] It can result in significant morbidity and can negatively affect quality of life. However, in recent years many new antiemetic medications and combinations have become available, dramatically decreasing the incidence and severity of this dreaded complication. Risk factors include the emetogenic potential of the specific drug, the dose used, the treatment schedule, and how chemotherapy agents are combined. For example, a drug with a low emetogenic potential given in high doses may cause a dramatic increase in the potential to induce N&V.[4] Standard doses of cytarabine rarely produce N&V, but N&V is often seen with high doses of this drug. Another influencing factor is the use of drug combinations. Because most patients receive combination chemotherapy, the emetogenic potential of all of the drugs combined and individual drug doses need to be considered.[5-9]

Other risk factors include the following:[10]

  • Poor control with previous chemotherapy.
  • Female gender.
  • Age younger than 50 years.
  • Experience with previous chemotherapy.
  • History of motion sickness.
  • History of pregnancy-induced N&V.
  • Dehydration.
  • Malnutrition.
  • Recent surgery.
  • Radiation therapy.

The American Society of Clinical Oncology has developed a rating system for chemotherapeutic agents and their respective risk of acute and delayed emesis.[11]

  • High risk: Emesis that has been documented to occur in more than 90% of patients:
    • Cisplatin.
    • Mechlorethamine.
    • Streptozotocin.
    • Cyclophosphamide, 1,500 mg/m2 or more.
    • Carmustine.
    • Dacarbazine.
    • Dactinomycin.
  • Moderate risk: Emesis that has been documented to occur in 30% to 90% of patients:
    • Carboplatin.
    • Cyclophosphamide, less than 1,500 mg/m2.
    • Daunorubicin.
    • Doxorubicin.
    • Epirubicin.
    • Idarubicin.
    • Oxaliplatin.
    • Cytarabine, more than 1 g/m2.
    • Ifosfamide.
    • Irinotecan.
  • Low risk: Emesis that has been documented to occur in 10% to 30% of patients:
    • Mitoxantrone.
    • Paclitaxel.
    • Docetaxel.
    • Mitomycin.
    • Topotecan.
    • Gemcitabine.
    • Etoposide.
    • Pemetrexed.
    • Methotrexate.
    • Cytarabine, less than 1,000 mg/m2.
    • Fluorouracil.
    • Bortezomib.
    • Cetuximab.
    • Trastuzumab.
  • Minimal risk: Emesis that has been documented to occur in fewer than 10% of patients:
    • Vinorelbine.
    • Bevacizumab.
    • Rituximab.
    • Bleomycin.
    • Vinblastine.
    • Vincristine.
    • Busulfan.
    • Fludarabine.
    • Cladribine.

Delayed N&V

Delayed (or late) N&V occurs more than 24 hours after chemotherapy administration. Delayed N&V is associated with cisplatin, cyclophosphamide, and other drugs (e.g., doxorubicin and ifosfamide) given at high doses or given on 2 or more consecutive days.[1,12,13]

  • Etiologies:
    • Patients who experience acute emesis with chemotherapy are significantly more likely to have delayed emesis.
  • Risk factors:
    • All predictive characteristics for acute emesis are considered risk factors for delayed emesis.
  • Emetic classifications:
References
  1. Hesketh PJ, Sanz-Altamira P, Bushey J, et al.: Prospective evaluation of the incidence of delayed nausea and vomiting in patients with colorectal cancer receiving oxaliplatin-based chemotherapy. Support Care Cancer 20 (5): 1043-7, 2012. [PUBMED Abstract]
  2. Schwartzberg L: Addressing the value of novel therapies in chemotherapy-induced nausea and vomiting. Expert Rev Pharmacoecon Outcomes Res 14 (6): 825-34, 2014. [PUBMED Abstract]
  3. Sekine I, Segawa Y, Kubota K, et al.: Risk factors of chemotherapy-induced nausea and vomiting: index for personalized antiemetic prophylaxis. Cancer Sci 104 (6): 711-7, 2013. [PUBMED Abstract]
  4. Roscoe JA, Morrow GR, Hickok JT, et al.: Nausea and vomiting remain a significant clinical problem: trends over time in controlling chemotherapy-induced nausea and vomiting in 1413 patients treated in community clinical practices. J Pain Symptom Manage 20 (2): 113-21, 2000. [PUBMED Abstract]
  5. Viale PH, Grande C, Moore S: Efficacy and cost: avoiding undertreatment of chemotherapy-induced nausea and vomiting. Clin J Oncol Nurs 16 (4): E133-41, 2012. [PUBMED Abstract]
  6. Dranitsaris G, Bouganim N, Milano C, et al.: Prospective validation of a prediction tool for identifying patients at high risk for chemotherapy-induced nausea and vomiting. J Support Oncol 11 (1): 14-21, 2013. [PUBMED Abstract]
  7. Kris MG, Urba SG, Schwartzberg LS: Clinical roundtable monograph. Treatment of chemotherapy-induced nausea and vomiting: a post-MASCC 2010 discussion. Clin Adv Hematol Oncol 9 (1): suppl 1-15, 2011. [PUBMED Abstract]
  8. Phillips RS, Gopaul S, Gibson F, et al.: Antiemetic medication for prevention and treatment of chemotherapy induced nausea and vomiting in childhood. Cochrane Database Syst Rev (9): CD007786, 2010. [PUBMED Abstract]
  9. Olver I, Clark-Snow RA, Ballatori E, et al.: Guidelines for the control of nausea and vomiting with chemotherapy of low or minimal emetic potential. Support Care Cancer 19 (Suppl 1): S33-6, 2011. [PUBMED Abstract]
  10. Kris MG, Hesketh PJ, Somerfield MR, et al.: American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 24 (18): 2932-47, 2006. [PUBMED Abstract]
  11. Navari RM: Antiemetic control: toward a new standard of care for emetogenic chemotherapy. Expert Opin Pharmacother 10 (4): 629-44, 2009. [PUBMED Abstract]
  12. Geling O, Eichler HG: Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications. J Clin Oncol 23 (6): 1289-94, 2005. [PUBMED Abstract]
  13. Fleishman SB, Mahajan D, Rosenwald V, et al.: Prevalence of Delayed Nausea and/or Vomiting in Patients Treated With Oxaliplatin-Based Regimens for Colorectal Cancer. J Oncol Pract 8 (3): 136-40, 2012. [PUBMED Abstract]

Prevention and Management of Acute or Delayed Nausea and Vomiting (Emesis)

Several organizations—including the American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the Pediatric Oncology Group of Ontario—have published antiemetic guidelines for their members. It is not the policy of PDQ to endorse specific guidelines, but examples can be found in the literature.[1-4]

Antiemetic agents are the most common intervention in the management of treatment-related nausea and vomiting (N&V). The basis for antiemetic therapy is the neurochemical control of vomiting. Although the exact mechanism is not well understood, peripheral neuroreceptors and the chemoreceptor trigger zone (CTZ) are known to contain receptors for serotonin, histamine (H1 and H2), dopamine, acetylcholine, opioids, and numerous other endogenous neurotransmitters.[5,6] Many antiemetics act by competitively blocking receptors for these substances, thereby inhibiting stimulation of peripheral nerves at the CTZ and possibly at the vomiting center.

Current guidelines [7,8] recommend that prechemotherapy management of chemotherapy-induced N&V (CINV) be based on the emetogenic potential of the chemotherapy agent(s) selected. For patients receiving regimens with high emetogenic potential, the combination of a 5-HT3 receptor antagonist, aprepitant, and dexamethasone is recommended prechemotherapy; lorazepam may also be used. Aprepitant and dexamethasone are recommended starting with chemotherapy for the prevention of delayed emesis.

For patients receiving moderately emetogenic chemotherapy, the combination of a 5-HT3 receptor antagonist and dexamethasone is used prechemotherapy, with or without lorazepam. Patients receiving the combination of an anthracycline and cyclophosphamide and select patients receiving certain other agents of moderate emetic risk, such as cisplatin (<50 mg/m2) or doxorubicin, may also receive aprepitant. Postchemotherapy, a 5-HT3 receptor antagonist, dexamethasone, or both are recommended for the prevention of delayed emesis.

For regimens with low emetogenic potential, dexamethasone is recommended with or without lorazepam. For regimens with minimal emetogenic risk, no prophylaxis is recommended.[7,8]

Antiemetic guidelines [7,8] have included the available oral 5-HT3 receptor antagonists as optional therapy for the prevention of delayed emesis, but the level of evidence supporting this practice is low.[9]

Studies have strongly suggested that patients experience more acute and delayed CINV than is perceived by practitioners.[9-11] One study suggested that patients who are highly expectant of experiencing nausea appear to experience more postchemotherapy nausea.[12] In addition, the current and new agents have been used as prophylaxis for acute and delayed CINV and have not been studied for use in established CINV. One study reported the effective use of intravenous (IV) palonosetron and dexamethasone for the prevention of CINV in patients receiving multiple-day chemotherapy.[13]

Pre- and postchemotherapy recommendations by emetogenic potential are summarized in Table 2.

Table 2. Antiemetic Recommendations by Emetic Risk Categoriesa
Emetic Risk Category ASCO Guidelines NCCN Guidelines
ASCO = American Society of Clinical Oncology; NCCN = National Comprehensive Cancer Network.
aAdapted from Navari.[14]
bOrder of listed antiemetics does not reflect preference.
High (>90%) risk Three-drug combination of a 5-HT3 receptor antagonist, dexamethasone, and aprepitant is recommended prechemotherapy. Prechemotherapy, a 5-HT3 receptor antagonist (ondansetron, granisetron, dolasetron, or palonosetronb), dexamethasone (12 mg), and aprepitant (125 mg) are recommended, with or without lorazepam.
For patients receiving cisplatin and all other agents of high emetic risk, the two-drug combination of dexamethasone and aprepitant is recommended for prevention of delayed emesis continuing for several days after the day of chemotherapy. For prevention of delayed emesis, dexamethasone (8 mg) on days 2–4 plus aprepitant (80 mg) on days 2 and 3 is recommended, with or without lorazepam on days 2–4. If the patient receives 150 mg of fosaprepitant on the day of chemotherapy, then days 2 and 3 of aprepitant are not needed.
Moderate (30%–90%) risk For patients receiving an anthracycline and cyclophosphamide, the three-drug combination of a 5-HT3 receptor antagonist, dexamethasone, and aprepitant is recommended prechemotherapy; aprepitant plus dexamethasone is recommended on days 2 and 3 for prevention of delayed emesis. For patients receiving an anthracycline and cyclophosphamide and selected patients receiving other chemotherapies of moderate emetic risk (e.g., carboplatin, cisplatin, doxorubicin, epirubicin, ifosfamide, irinotecan, or methotrexate), a 5-HT3 receptor antagonist (ondansetron, granisetron, dolasetron, or palonosetronb), dexamethasone (12 mg), and aprepitant (125 mg) are recommended, with or without lorazepam, prechemotherapy; for other patients, aprepitant is not recommended.
For patients receiving other chemotherapies of moderate emetic risk, the two-drug combination of a 5-HT3 receptor antagonist and dexamethasone is recommended prechemotherapy; single-agent dexamethasone or a 5-HT3 receptor antagonist is recommended on days 2 and 3 for prevention of delayed emesis. For prevention of delayed emesis, dexamethasone (8 mg) or a 5-HT3 receptor antagonist on days 2–4 or, if used on day 1, aprepitant (80 mg) on days 2 and 3, with or without dexamethasone (8 mg) on days 2–4, is recommended, with or without lorazepam on days 2–4.
Low (10%–30%) risk Dexamethasone (8 mg) is recommended; no routine preventive use of antiemetics for delayed emesis recommended. Metoclopramide, with or without diphenhydramine; dexamethasone (12 mg); or prochlorperazine is recommended, with or without lorazepam.
Minimal (<10%) risk No antiemetic is administered routinely pre- or postchemotherapy. No routine prophylaxis; consider using antiemetics listed under primary prophylaxis as treatment.

Most drugs with proven antiemetic activity can be categorized into one of the following groups:

  • Competitive antagonists at dopaminergic (D2 subtype) receptors:
    • Phenothiazines.
    • Butyrophenones (droperidol, haloperidol).
    • Substituted benzamides (metoclopramide).
  • Competitive antagonists at serotonergic (5-hydroxytryptamine-3 or 5-HT3 subtype) receptors.
  • Substance P antagonists (neurokinin-1 [NK-1] receptor antagonists).
  • Corticosteroids.
  • Benzodiazepines (lorazepam).
  • Cannabinoids.

Although all routes of administration are listed for each of the following drugs, the intramuscular (IM) route is used only when no other access is available. IM delivery is painful, is associated with erratic absorption of drug, and may lead to sterile abscess formation or fibrosis of the tissues. This is particularly important when more than one or two doses of a drug are to be given.

Phenothiazines

Phenothiazines act on dopaminergic receptors at the CTZ, possibly at other central nervous system (CNS) centers, and peripherally. With the exception of thioridazine, many phenothiazines possess antiemetic activity, including chlorpromazine given in the 10- to 50-mg dose range orally, IM, IV, and rectally (pediatric dose for patients >12 years: 10 mg every 6–8 hours; for patients <12 years: 5 mg every 6–8 hours); and perphenazine.

The primary consideration in selecting phenothiazines are differences in their adverse effect profiles, which substantially correlate with their structural classes. Generally, aliphatic phenothiazines (e.g., chlorpromazine, methotrimeprazine) produce sedation and anticholinergic effects, while piperazines (e.g., prochlorperazine, perphenazine, fluphenazine) are associated with less sedation but greater incidence of extrapyramidal reactions (EPRs) (acute dystonias, akathisia, neuroleptic malignant syndrome [uncommon], and, rarely, akinesias and dyskinesias). Marked hypotension may also result if IV doses are administered rapidly at high doses. The concomitant use of H1 blockers, such as diphenhydramine, can often decrease the risk and severity of extrapyramidal side effects. Phenothiazines may be of particular value in treating patients who experience delayed N&V (postacute phase symptoms) on cisplatin regimens.[15-19][Level of evidence: I]

Butyrophenones

Droperidol and haloperidol represent butyrophenones, another class of dopaminergic (D2 subtype) receptor antagonists that are structurally and pharmacologically similar to the phenothiazines. While droperidol is used primarily as an adjunct to anesthesia induction, haloperidol is indicated as a neuroleptic antipsychotic drug; however, both agents have some antiemetic activity. Droperidol is administered IM or IV, typically from 1 to 2.5 mg every 2 to 6 hours, but higher doses (up to 10 mg) have been safely given.[20,21] Haloperidol is administered IM, IV, or orally, typically from 1 to 4 mg every 2 to 6 hours.[22] Results of a small, uncontrolled, open-label study showed some efficacy for haloperidol in palliative care patients.[23] Both agents may produce EPRs, akathisia, hypotension, and sedation.

Substituted Benzamides

Metoclopramide is a substituted benzamide, which, before serotonin (5-HT3) receptor antagonists were introduced, was considered the most effective single antiemetic agent against highly emetogenic chemotherapy such as cisplatin. Although metoclopramide is a competitive antagonist at dopaminergic (D2) receptors, it is most effective against acute vomiting when given IV at high doses (e.g., 0.5–3 mg/kg/dose), probably because it is a weak competitive antagonist (relative to other serotonin antagonists) at 5-HT3 receptors. It may act on the CTZ and the periphery. Metoclopramide also increases lower esophageal sphincter pressure and enhances the rate of gastric emptying, which may factor into its overall antiemetic effect. It can be administered IV at the U.S. Food and Drug Administration (FDA)–approved dose of 1 to 2 mg/kg every 2 hours (or less frequently) for three to five doses. Metoclopramide has also been safely given by IV bolus injection at higher single doses (up to 6 mg/kg) and by continuous IV infusion, with or without a loading bolus dose, with efficacy comparable to that of multiple intermittent dosing schedules.[24-26]

Metoclopramide is associated with akathisia and dystonic extrapyramidal effects; akathisia is seen more frequently in patients older than 30 years, and dystonic extrapyramidal effects are seen more commonly in patients younger than 30 years. Diphenhydramine, benztropine mesylate, and trihexyphenidyl are commonly used prophylactically or therapeutically to pharmacologically antagonize EPRs.[27] While cogwheeling rigidity, acute dystonia, and tremor are responsive to anticholinergic medications, akathisia—the subjective sense of restlessness or inability to sit still—is best treated by the following:

  • Switching to a lower potency neuroleptic for vomiting, if possible.
  • Lowering the dose.
  • Adding a benzodiazepine (e.g., lorazepam).

Although less commonly used in the United States, metoclopramide is still very commonly used in other countries.

5-HT3 Receptor Antagonists

Four serotonin receptor antagonists—ondansetron, granisetron, dolasetron, and palonosetron—are available in the United States. Tropisetron, while not approved by the FDA, is available internationally. Agents in this class are thought to prevent N&V by preventing serotonin, which is released from enterochromaffin cells in the gastrointestinal (GI) mucosa, from initiating afferent transmission to the CNS via vagal and spinal sympathetic nerves.[28-30] The 5-HT3 receptor antagonists may also block serotonin stimulation at the CTZ and other CNS structures. Major side effects of this class of medications include mild headache, constipation, and/or diarrhea. Multiple studies have shown that the 5-HT3 receptor antagonists are most effective when given in conjunction with steroids.

Comparison of agents

Studies suggest that there are no major differences in efficacy or toxicity of the three first-generation 5-HT3 receptor antagonists (dolasetron, granisetron, and ondansetron) in the treatment of acute CINV. These three agents are equivalent in efficacy and toxicity when used in appropriate doses.[31,32]; [33][Level of evidence: I] Although these agents have been shown to be effective in the first 24 hours postchemotherapy (acute phase), they have not been demonstrated to be effective in days 2 to 5 postchemotherapy (delayed phase).

Palonosetron, the second-generation 5-HT3 receptor antagonist, has been approved for the control of acute emesis with highly and moderately emetogenic chemotherapy and delayed emesis for patients receiving moderately emetogenic chemotherapy.[34]; [35][Level of evidence: I]

Despite the use of both first-generation and second-generation 5-HT3 receptor antagonists, the control of acute CINV, and especially delayed N&V, is suboptimal, and there is considerable opportunity for improvement with either the addition or substitution of new agents in current regimens.[9,36-38]

Ondansetron

Several studies have demonstrated that ondansetron produces an antiemetic response that equals or is superior to that of high doses of metoclopramide, but ondansetron has an improved toxicity profile, compared with that of dopaminergic antagonist agents.[39-42][Level of evidence: I][43,44] Ondansetron (0.15 mg/kg) is given IV 15 to 30 minutes before chemotherapy and is repeated every 4 hours for two additional doses. Alternatively, for patients older than 18 years, a large multicenter study determined that a single 32-mg dose of ondansetron is more effective in treating cisplatin-induced N&V than a single 8-mg dose and is as effective as the standard regimen of three doses at 0.15 mg/kg given every 4 hours starting 30 minutes before chemotherapy.[45][Level of evidence: I] A single-center retrospective chart review has reported ondansetron-loading doses of 16 mg/m2 (maximum, 24 mg) IV to be safe in infants, children, and adolescents.[46] However, data reported to the FDA raises concern about QT prolongation and potentially fatal arrhythmias with a single IV dose of 32 mg. Current drug labeling calls for a maximal single IV dose of 16 mg.[47]

Currently, the oral and injectable ondansetron formulations are approved for use without dosage modification in patients older than 4 years, including elderly patients and patients with renal insufficiency. Oral ondansetron is given 3 times daily starting 30 minutes before chemotherapy and continuing for up to 2 days after chemotherapy is completed. Ondansetron clearance is diminished in patients with severe hepatic insufficiency; therefore, such patients receive a single injectable or oral dose no higher than 8 mg. There is currently no information evaluating the safety of repeated daily ondansetron doses in patients with hepatic insufficiency. Other effective dosing schedules such as a continuous IV infusion (e.g., 1 mg/h for 24 h) or oral administration have also been evaluated.[45]

The major adverse effects include the following:[48]

  • Headache (which can be treated with mild analgesics).
  • Constipation or diarrhea.
  • Fatigue.
  • Dry mouth.
  • Transient asymptomatic elevations in liver function tests (alanine and aspartate transaminases), which may be related to concurrent cisplatin administration.

Ondansetron has been etiologically implicated in a few case studies involving thrombocytopenia, renal insufficiency, and thrombotic events.[49] In addition, a few case reports have implicated ondansetron in causing EPRs. However, it is not clear in some cases whether the events described were in fact EPRs; in other reports, the evidence is confounded by concurrent use of other agents that are known to produce EPRs. Nevertheless, the greatest advantage of serotonin receptor antagonists over dopaminergic receptor antagonists is that they have fewer adverse effects. Despite prophylaxis with ondansetron, many patients receiving doxorubicin, cisplatin, or carboplatin will experience acute and delayed-phase N&V.[50] A randomized, double-blind, placebo-controlled trial suggests that the addition of aprepitant, an NK-1 receptor antagonist, may mitigate N&V.[51] The optimal dose of aprepitant may be 125 mg on day 1 followed by 80 mg on days 2 and 3.[52,53][Level of evidence: I]

Granisetron

Granisetron has demonstrated efficacy in preventing and controlling N&V at a broad range of doses (e.g., 10–80 µg/kg and empirically, 3 mg/dose). In the United States, granisetron injection, transdermal patch, and oral tablets are approved for initial and repeat prophylaxis for patients receiving emetogenic chemotherapy, including high-dose cisplatin. Granisetron is pharmacologically and pharmacokinetically distinct from ondansetron; however, clinically it is equally efficacious and equally safe.[50,51,53,54][Level of evidence: I] Both granisetron formulations are given before chemotherapy, either as a single IV dose of 10 µg/kg (0.01 mg/kg) or as 1 mg orally every 12 hours.

Both granisetron formulations and ondansetron injection share the same indication against highly emetogenic chemotherapy. In contrast, the oral ondansetron formulation has been approved only for use against N&V associated with moderately emetogenic chemotherapy.

Currently, granisetron injection is approved for use without dosage modification in patients older than 2 years, including elderly patients and patients with hepatic and renal insufficiency. Oral granisetron has not yet been approved for use in pediatric patients.

Dolasetron

Oral formulations of dolasetron are indicated for the prevention of N&V associated with moderately emetogenic cancer chemotherapy, including initial and repeat courses. Oral dolasetron may be dosed as 100 mg within 1 hour before chemotherapy. Dolasetron is given IV or orally at 1.8 mg/kg as a single dose approximately 30 minutes before chemotherapy. Injection formulations are no longer approved for CINV because of the risk of QTc interval prolongation.[55]

The effectiveness of oral dolasetron in the prevention of CINV has been proven in a large randomized, double-blind, comparative trial of 399 patients.[56][Level of evidence: I] Oral dolasetron was administered in the range of 25 to 200 mg 1 hour before chemotherapy. The other study arm consisted of oral ondansetron (8 mg) administered 1.5 hours before chemotherapy and every 8 hours after chemotherapy for a total of three doses. Complete response (CR) rates improved with increasing doses of dolasetron. Both dolasetron 200 mg and ondansetron had significantly higher CR rates than did dolasetron 25 or 50 mg. (CR was defined as no emetic episodes and no use of escape antiemetic medications.)

Palonosetron

Palonosetron is a 5-HT3 receptor antagonist (second generation) that has antiemetic activity at both central and GI sites. Palonosetron is FDA approved for the prevention of acute N&V associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy and for the prevention of delayed N&V associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. Compared with the older 5-HT3 receptor antagonists, palonosetron has a higher binding affinity to the 5-HT3 receptors, a higher potency, a significantly longer half-life (approximately 40 hours, four to five times longer than that of dolasetron, granisetron, or ondansetron), and an excellent safety profile.[57][Level of evidence: I] A dose-finding study demonstrated that the effective dose was 0.25 mg or higher.[58-62]

In two large studies of patients receiving moderately emetogenic chemotherapy, CR (no emesis, no rescue) was significantly improved in the acute and the delayed period for patients who received 0.25 mg of palonosetron alone, compared with either ondansetron or dolasetron alone.[34]; [35][Level of evidence: I] Dexamethasone was not given with the 5-HT3 receptor antagonists in these studies, and it is not yet known whether the differences in CR would persist if dexamethasone was used. In another study,[63][Level of evidence: I] 650 patients receiving highly emetogenic chemotherapy (cisplatin ≥60 mg/m2) also received either dexamethasone and one of two doses of palonosetron (0.25 mg or 0.75 mg) or dexamethasone and ondansetron (32 mg). Single-dose palonosetron was as effective as ondansetron in preventing acute CINV with dexamethasone pretreatment; it was significantly more effective than ondansetron throughout the 5-day postchemotherapy period. In an analysis of the patients in the above studies who received repeated cycles of chemotherapy, one author [64] reported that the CR rates for both acute and delayed CINV were maintained with single IV doses of palonosetron without concomitant corticosteroids.

Substance P Antagonists (NK-1 Receptor Antagonists)

Substance P, found in the vagal afferent neurons in the nucleus tractus solitarius, the abdominal vagus, and the area postrema, induces vomiting. NK-1 receptor antagonists, including aprepitant, fosaprepitant, and netupitant, have been developed.

Aprepitant

The initial clinical studies using the NK-1 receptor antagonists [65-68] demonstrated that the addition of aprepitant (CP-122,721, CJ-11,794, MK-0869) to a 5-HT3 receptor antagonist plus dexamethasone before cisplatin chemotherapy improved the control of acute emesis, compared with a 5-HT3 receptor antagonist plus dexamethasone; this regimen also improved the control of delayed emesis, compared with placebo. In addition, as a single agent, aprepitant had an effect similar to that of ondansetron on cisplatin-induced acute emesis but was superior in the control of delayed emesis.

Subsequent studies [69,70][Level of evidence: I] showed that the combination of aprepitant and dexamethasone was inferior in controlling acute emesis, compared with triple therapy (aprepitant, 5-HT3 receptor antagonist, and dexamethasone). These studies also confirmed the improvement of delayed emesis with the use of aprepitant, compared with placebo. Two studies [71,72][Level of evidence: I] have also shown an improvement in cisplatin-induced delayed emesis with the combination of aprepitant and dexamethasone, compared with dexamethasone alone, with the improvement maintained over repeat cycles of cisplatin chemotherapy.

In two randomized, double-blind, parallel, multicenter, controlled studies (520 patients in each study), patients received cisplatin (≥70 mg/m2) and were randomly assigned to receive either standard therapy with a 5-HT3 receptor antagonist (ondansetron) and dexamethasone prechemotherapy and dexamethasone postchemotherapy (days 2–4); or standard therapy plus aprepitant prechemotherapy and on days 2 and 3 postchemotherapy.[52,73][Level of evidence: I] The CR (no emesis, no rescue) of the aprepitant group in both studies was significantly higher in both the acute period (83%–89%) and the delayed period (68%–75%), compared with the CR of the standard therapy group in the acute period (68%–78%) and delayed period (47%–56%). Nausea was improved in the aprepitant group for some, but not all of the various specific measures of nausea.

The studies discussed above formed the basis for the approval of aprepitant by the FDA in March 2003. In combination with other antiemetics, aprepitant is indicated for the prevention of acute and delayed N&V associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin. An additional study confirmed the efficacy of aprepitant in the delayed period, when it was compared with ondansetron.[74][Level of evidence: I] Another randomized phase III trial studied the use of aprepitant, granisetron, and dexamethasone for the prevention of CINV in multiple myeloma transplant patients receiving high-dose melphalan with autologous stem cell transplantation. A statistically positive benefit, without an increase in side effects, was seen in patients who were given this regimen.[75-79]

Fosaprepitant

Fosaprepitant is a prodrug for aprepitant and is available in IV formulation. It is indicated in patients who are unable to tolerate oral medications because of mucositis, swallowing difficulties, or GI disturbance. Preliminary studies have shown safety and efficacy similar to that of oral aprepitant. Fosaprepitant is approved at a dose of 115 mg on day 1, followed by oral aprepitant on days 2 and 3. Fosaprepitant dimeglumine, a water-soluble, phosphorylated analog of aprepitant, is rapidly converted to aprepitant after IV administration.[80] Fosaprepitant (115 mg) was approved by the FDA as an alternative to the 125-mg oral aprepitant dose on day 1 of a 3-day regimen. As demonstrated in a randomized, double-blind study of patients receiving cisplatin chemotherapy, single-dose IV fosaprepitant (150 mg) given with ondansetron and dexamethasone was noninferior to the standard 3-day dosing of oral aprepitant in preventing CINV.[81]

Netupitant

Netupitant is a competitive antagonist to the NK-1 receptor that is marketed as an oral fixed-combination product containing 300 mg of netupitant and 0.5 mg of palonosetron; it is dosed as a single product with dexamethasone before chemotherapy for the prevention of both acute and delayed CINV. This drug combination has been used successfully for prevention in both highly and moderately emetogenic chemotherapy regimens.[82,83]

Corticosteroids

Steroids are commonly used in combination with other antiemetics. Their antiemetic mechanism of action is not fully understood, but they may affect prostaglandin activity in the brain. Clinically, steroids quantitatively decrease or eliminate episodes of N&V and may improve patients’ mood, thus producing a subjective sense of well-being or euphoria (although they also can cause depression and anxiety). Steroids are sometimes used as single agents against mildly to moderately emetogenic chemotherapy but are more often used in antiemetic drug combinations.[84,85][Level of evidence: I][86]

Steroids are often given IV before chemotherapy and may or may not be repeated. Dosages and administration schedules are selected empirically. Dexamethasone is often the treatment of choice for N&V in patients receiving radiation to the brain, as it also reduces cerebral edema. It is administered orally or IV in the dose range of 8 mg to 40 mg (pediatric dose: 0.25–0.5 mg/kg).[87,88] Methylprednisolone is also administered orally, or IV at doses and schedules that vary from 40 mg to 500 mg every 6 to 12 hours for up to 20 doses.[85,89]

Dexamethasone is also used orally for delayed N&V. Long-term corticosteroid use, however, is inappropriate and may cause substantial morbidity, including the following:[90-92]

  • Immunosuppression.
  • Proximal muscle weakness (especially involving the thighs and upper arms).
  • Aseptic necrosis of the long bones.
  • Cataract formation.
  • Hyperglycemia and exacerbation of preexisting diabetes or escalation of subclinical diabetes to clinical pathology.
  • Adrenal suppression with hypocortisolism.
  • Lethargy.
  • Weight gain.
  • GI irritation.
  • Insomnia.
  • Anxiety.
  • Mood changes.
  • Psychosis.

A study that examined chemotherapy in a group of patients with ovarian cancer found that short-term use of glucocorticoids as antiemetics had no negative effects on outcomes (e.g., overall survival or efficacy of chemotherapy).[93] As previously shown with metoclopramide, numerous studies have demonstrated that dexamethasone potentiates the antiemetic properties of 5-HT3–blocking agents.[90,94] If administered IV, dexamethasone may be given over 10 to 15 minutes because rapid administration may cause sensations of generalized warmth, pharyngeal tingling or burning, or acute transient perineal and/or rectal pain.[95-98]

Benzodiazepines

Benzodiazepines such as lorazepam, midazolam, and alprazolam have become recognized as valuable adjuncts in the prevention and treatment of anxiety and the symptoms of anticipatory N&V associated with chemotherapy, especially with the highly emetogenic regimens given to children.[90-92] Benzodiazepines have not demonstrated intrinsic antiemetic activity as single agents; therefore, their place in antiemetic prophylaxis and treatment is adjunctive to other antiemetic agents.[99] Benzodiazepines presumably act on higher CNS structures, the brainstem, and spinal cord, and they produce anxiolytic, sedative, and anterograde amnesic effects. In addition, benzodiazepines markedly decrease the severity of EPRs, especially akathisia, associated with dopaminergic receptor antagonist antiemetics.

Lorazepam

Lorazepam may be administered orally, IV, and sublingually. Dosages range from 0.5 to 3 mg (alternatively, 0.025–0.05 mg/kg, or 1.5 mg/m2, but ≤4 mg per dose) in adults and 0.03 to 0.05 mg/kg in children every 6 to 12 hours.[100][Level of evidence: I][101,102] Midazolam produces mild-to-marked sedation for 1 to 4.5 hours at doses equal to 0.04 mg/kg given IV over 3 to 5 minutes.[103,104] Alprazolam has been shown to be effective when given in combination with metoclopramide and methylprednisolone.[105]

The adverse effects of lorazepam include the following:[106]

  • Sedation.
  • Perceptual disturbances.
  • Disorders of micturition and/or defecation.
  • Visual disturbances.
  • Hypotension.
  • Anterograde amnesia.
  • Psychological dependence.
  • Confusion.
  • Ataxia.
  • Depressed mental acuity with intoxication.

Olanzapine

Olanzapine is an antipsychotic in the thienobenzodiazepine drug class that blocks multiple neurotransmitters: dopamine at D1, D2, D3, and D4 brain receptors; serotonin at 5-HT2a, 5-HT2c, 5-HT3, and 5-HT6 receptors; catecholamines at alpha-1 adrenergic receptors; acetylcholine at muscarinic receptors; and histamine at H1 receptors.[107] Common side effects include the following:[108,109]

  • Sedation.
  • Dry mouth.
  • Increased appetite.
  • Weight gain.
  • Postural hypotension.
  • Dizziness.

Olanzapine has also been associated with increased risk of hyperlipidemia, hyperglycemia, new-onset diabetes and, in rare cases, diabetic ketoacidosis.[110,111] Olanzapine is used with caution in elderly patients; it has been associated with increased risk of death and increased incidence of cerebrovascular adverse events in patients with dementia-related psychosis and carries a boxed warning to that effect. Olanzapine's activity at multiple receptors, particularly at the D2 and 5-HT3 receptors that appear to be involved in N&V, suggests that it may have significant antiemetic properties.[112][Level of evidence: II]; [113,114]

A phase I study used olanzapine for the prevention of delayed emesis in cancer patients receiving their first cycle of chemotherapy consisting of cyclophosphamide, doxorubicin, cisplatin, and/or irinotecan.[115] The protocol was completed by 15 patients, and no grade 4 toxicities were observed. The maximum tolerated dose was 5 mg/day for 2 days before chemotherapy and 10 mg/day for 7 days postchemotherapy. On the basis of these phase I data, olanzapine appeared to be a safe and effective agent for the prevention of delayed emesis in chemotherapy-naive cancer patients receiving cyclophosphamide, doxorubicin, cisplatin, and/or irinotecan.

Using the maximum tolerated dose of olanzapine in the phase I trial, a phase II trial was performed for the prevention of CINV in patients receiving their first course of either highly emetogenic or moderately emetogenic chemotherapy.[116][Level of evidence: II] Olanzapine was added to granisetron and dexamethasone prechemotherapy and to dexamethasone postchemotherapy. CR (no emesis, no rescue) was 100% for the acute period (24 hours postchemotherapy), 80% for the delayed period (days 2–5 postchemotherapy), and 80% for the overall period (0–120 hours postchemotherapy) in ten patients receiving highly emetogenic chemotherapy (cisplatin, ≥70 mg/m2). CR was also 100% for the acute period, 85% for the delayed period, and 85% for the overall period in 20 patients receiving moderately emetogenic chemotherapy (doxorubicin, ≥50 mg/m2). Nausea was very well controlled in the patients receiving highly emetogenic chemotherapy, with no patient having nausea (0 on a scale of 0–10 on the MD Anderson Symptom Inventory) in the acute or delayed periods. Nausea was also well controlled in patients receiving moderately emetogenic chemotherapy, with no nausea in 85% of patients in the acute period and in 65% of patients in the delayed and overall periods. There were no grade 3 or 4 toxicities. On the basis of these data, olanzapine appeared to be safe (sedation was the only dose-limiting toxicity) and effective in controlling acute and delayed CINV in patients receiving highly emetogenic and moderately emetogenic chemotherapy in these very small preliminary studies.[116][Level of evidence: II]

Subsequent studies have shown the effectiveness of olanzapine as an antiemetic. Olanzapine combined with a single dose of dexamethasone and a single dose of palonosetron was very effective in controlling acute and delayed CINV in patients receiving either moderately emetogenic chemotherapy or highly emetogenic chemotherapy.[117] A large end study [118][Level of evidence: I] demonstrated that in patients receiving either highly emetogenic chemotherapy or moderately emetogenic chemotherapy, the addition of olanzapine to azasetron and dexamethasone improved the CR of delayed CINV.

Other Pharmacologic Agents

Cannabis

The plant Cannabis contains more than 60 different types of cannabinoids, or components that have physiologic activity. The most popular, and perhaps the most psychoactive, is delta-9-tetrahydrocannabinol (delta-9-THC).[119] There are two FDA-approved Cannabis products for CINV:

  • Dronabinol (a synthetic delta-9-THC), as prophylaxis for CINV, 5 mg/m2 orally 1 to 3 hours before chemotherapy and every 2 to 4 hours after chemotherapy, for a total of no more than 6 doses per day.
  • Nabilone, for CINV that has failed to respond to other antiemetics, 1 to 2 mg orally twice a day.

With respect to CINV, Cannabis products probably target cannabinoid-1 (CB-1) and CB-2 receptors, which are in the CNS.[120] Another product, Sativex, contains a combination of delta-9-THC and cannabidiol and is a buccal spray; it is under clinical investigation.[121,122]

Much of the research on this class of agent was conducted in the late 1970s and 1980s and compared nabilone, dronabinol, or levonantradol to older antiemetic agents that targeted the dopamine receptor, such as prochlorperazine (Compazine) and metoclopramide (Reglan).[123-127] This group of studies demonstrated that cannabinoids were as effective for moderately emetogenic chemotherapy as dopaminergic antiemetics or were more effective than placebo.[119] Side effects included euphoria, dizziness, dysphoria, hallucinations, and hypotension.[119] Despite earlier reports of efficacy, in at least one study, patients did not significantly prefer nabilone because of the side effects.[123]

Since the 1990s, research in N&V has elucidated newer and more physiologic targets, namely 5-HT3 and NK-1 receptors. Subsequently, 5-HT3 and NK-1 receptor antagonists have become standard prophylactic therapy for CINV. Studies investigating the role of Cannabis extract and cannabinoids with these newer agents are few; therefore, limited conclusions can be drawn. In published trials, however, Cannabis extract and cannabinoids have not demonstrated more efficacy than 5-HT3 receptor antagonists, and synergistic or additive effects have not been fully investigated.[128,129]

In summary, the place of Cannabis and cannabinoids in today’s arsenal of antiemetics for the prevention and treatment of CINV is not known. Discussions with patients about its use may include responses to available agents, known side effects of Cannabis, and an assessment of the risks versus benefits of this therapy.[130]

Refer to the PDQ summary on Cannabis and Cannabinoids for a broader discussion of the issues surrounding Cannabis use.

Ginger

A phase III, randomized, dose-finding trial of 576 patients with cancer evaluated 0.5 g, 1 g, and 1.5 g of ginger versus placebo in twice-a-day dosing for the prevention of acute nausea (defined as day 1 postchemotherapy) in patients experiencing some level of nausea (as measured on an 11-point scale) caused by their current chemotherapy regimen, despite standard prophylaxis with a 5-HT3 receptor antagonist. Patients began taking ginger or placebo capsules 3 days before each chemotherapy treatment and continued them for 6 days. For average nausea, 0.5 g of ginger was significantly better than placebo; both 0.5 g and 1 g were significantly better than placebo for “worst nausea.” Effects for delayed N&V were not significant. This trial did not control for emetogenicity of the chemotherapy regimens. Adverse events were infrequent and were not severe.[131]

Current Clinical Trials

Check NCI’s list of cancer clinical trials for U.S. supportive and palliative care trials about nausea and vomiting therapy that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References
  1. García Gómez J, Pérez López ME, García Mata J, et al.: SEOM clinical guidelines for the treatment of antiemetic prophylaxis in cancer patients receiving chemotherapy. Clin Transl Oncol 12 (11): 770-4, 2010. [PUBMED Abstract]
  2. Basch E, Prestrud AA, Hesketh PJ, et al.: Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 29 (31): 4189-98, 2011. [PUBMED Abstract]
  3. Dupuis LL, Boodhan S, Holdsworth M, et al.: Guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer 60 (7): 1073-82, 2013. [PUBMED Abstract]
  4. Dupuis LL, Robinson PD, Boodhan S, et al.: Guideline for the prevention and treatment of anticipatory nausea and vomiting due to chemotherapy in pediatric cancer patients. Pediatr Blood Cancer 61 (8): 1506-12, 2014. [PUBMED Abstract]
  5. Hesketh PJ: Understanding the pathobiology of chemotherapy-induced nausea and vomiting. Providing a basis for therapeutic progress. Oncology (Williston Park) 18 (10 Suppl 6): 9-14, 2004. [PUBMED Abstract]
  6. Rudd JA, Andrews PLR: Mechanisms of acute, delayed, and anticipatory emesis induced by anticancer therapies. In: Hesketh PJ, ed.: Management of Nausea and Vomiting in Cancer and Cancer Treatment. Sudbury, Mass: Jones and Bartlett Publishers, Inc., 2005, pp 15-66.
  7. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Antiemesis. Version 1.2015. Fort Washington, Pa: National Comprehensive Cancer Network, 2015. Available online. Last accessed June 25, 2015.
  8. Kris MG, Hesketh PJ, Somerfield MR, et al.: American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 24 (18): 2932-47, 2006. [PUBMED Abstract]
  9. Navari RM: Pathogenesis-based treatment of chemotherapy-induced nausea and vomiting--two new agents. J Support Oncol 1 (2): 89-103, 2003 Jul-Aug. [PUBMED Abstract]
  10. Grunberg SM, Deuson RR, Mavros P, et al.: Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer 100 (10): 2261-8, 2004. [PUBMED Abstract]
  11. Fabi A, Barduagni M, Lauro S, et al.: Is delayed chemotherapy-induced emesis well managed in oncological clinical practice? An observational study. Support Care Cancer 11 (3): 156-61, 2003. [PUBMED Abstract]
  12. Colagiuri B, Roscoe JA, Morrow GR, et al.: How do patient expectancies, quality of life, and postchemotherapy nausea interrelate? Cancer 113 (3): 654-61, 2008. [PUBMED Abstract]
  13. Einhorn LH, Brames MJ, Dreicer R, et al.: Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for germ cell cancer. Support Care Cancer 15 (11): 1293-300, 2007. [PUBMED Abstract]
  14. Navari RM: Overview of the updated antiemetic guidelines for chemotherapy-induced nausea and vomiting. Community Oncology 4 (4 Suppl 1): 3-11, 2007. Also available online. Last accessed June 25, 2015.
  15. Olver IN, Webster LK, Bishop JF, et al.: A dose finding study of prochlorperazine as an antiemetic for cancer chemotherapy. Eur J Cancer Clin Oncol 25 (10): 1457-61, 1989. [PUBMED Abstract]
  16. Carr BI, Bertrand M, Browning S, et al.: A comparison of the antiemetic efficacy of prochlorperazine and metoclopramide for the treatment of cisplatin-induced emesis: a prospective, randomized, double-blind study. J Clin Oncol 3 (8): 1127-32, 1985. [PUBMED Abstract]
  17. Olver IN, Wolf M, Laidlaw C, et al.: A randomised double-blind study of high-dose intravenous prochlorperazine versus high-dose metoclopramide as antiemetics for cancer chemotherapy. Eur J Cancer 28A (11): 1798-802, 1992. [PUBMED Abstract]
  18. Levinson DF, Simpson GM: Neuroleptic-induced extrapyramidal symptoms with fever. Heterogeneity of the 'neuroleptic malignant syndrome'. Arch Gen Psychiatry 43 (9): 839-48, 1986. [PUBMED Abstract]
  19. Wampler G: The pharmacology and clinical effectiveness of phenothiazines and related drugs for managing chemotherapy-induced emesis. Drugs 25 (Suppl 1): 35-51, 1983. [PUBMED Abstract]
  20. Mason BA, Dambra J, Grossman B, et al.: Effective control of cisplatin-induced nausea using high-dose steroids and droperidol. Cancer Treat Rep 66 (2): 243-5, 1982. [PUBMED Abstract]
  21. Kelley SL, Braun TJ, Meyer TJ, et al.: Trial of droperidol as an antiemetic in cisplatin chemotherapy. Cancer Treat Rep 70 (4): 469-72, 1986. [PUBMED Abstract]
  22. Plotkin DA, Plotkin D, Okun R: Haloperidol in the treatment of nausea and vomiting due to cytotoxic drug administration. Curr Ther Res Clin Exp 15 (9): 599-602, 1973. [PUBMED Abstract]
  23. Hardy JR, O'Shea A, White C, et al.: The efficacy of haloperidol in the management of nausea and vomiting in patients with cancer. J Pain Symptom Manage 40 (1): 111-6, 2010. [PUBMED Abstract]
  24. Navari RM: Comparison of intermittent versus continuous infusion metoclopramide in control of acute nausea induced by cisplatin chemotherapy. J Clin Oncol 7 (7): 943-6, 1989. [PUBMED Abstract]
  25. Agostinucci WA, Gannon RH, Golub GR, et al.: Continuous i.v. infusion versus multiple bolus doses of metoclopramide for prevention of cisplatin-induced emesis. Clin Pharm 7 (6): 454-7, 1988. [PUBMED Abstract]
  26. Kris MG, Gralla RJ, Tyson LB, et al.: Improved control of cisplatin-induced emesis with high-dose metoclopramide and with combinations of metoclopramide, dexamethasone, and diphenhydramine. Results of consecutive trials in 255 patients. Cancer 55 (3): 527-34, 1985. [PUBMED Abstract]
  27. Kris MG, Tyson LB, Gralla RJ, et al.: Extrapyramidal reactions with high-dose metoclopramide. N Engl J Med 309 (7): 433-4, 1983. [PUBMED Abstract]
  28. Hsu ES: A review of granisetron, 5-hydroxytryptamine3 receptor antagonists, and other antiemetics. Am J Ther 17 (5): 476-86, 2010 Sep-Oct. [PUBMED Abstract]
  29. Trammel M, Roederer M, Patel J, et al.: Does pharmacogenomics account for variability in control of acute chemotherapy-induced nausea and vomiting with 5-hydroxytryptamine type 3 receptor antagonists? Curr Oncol Rep 15 (3): 276-85, 2013. [PUBMED Abstract]
  30. Hatoum HT, Lin SJ, Buchner D, et al.: Comparative clinical effectiveness of various 5-HT3 RA antiemetic regimens on chemotherapy-induced nausea and vomiting associated with hospital and emergency department visits in real world practice. Support Care Cancer 20 (5): 941-9, 2012. [PUBMED Abstract]
  31. Aogi K, Sakai H, Yoshizawa H, et al.: A phase III open-label study to assess safety and efficacy of palonosetron for preventing chemotherapy-induced nausea and vomiting (CINV) in repeated cycles of emetogenic chemotherapy. Support Care Cancer 20 (7): 1507-14, 2012. [PUBMED Abstract]
  32. Hesketh PJ: Comparative review of 5-HT3 receptor antagonists in the treatment of acute chemotherapy-induced nausea and vomiting. Cancer Invest 18 (2): 163-73, 2000. [PUBMED Abstract]
  33. Navari R, Gandara D, Hesketh P, et al.: Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group. J Clin Oncol 13 (5): 1242-8, 1995. [PUBMED Abstract]
  34. Eisenberg P, Figueroa-Vadillo J, Zamora R, et al.: Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer 98 (11): 2473-82, 2003. [PUBMED Abstract]
  35. Gralla R, Lichinitser M, Van Der Vegt S, et al.: Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 14 (10): 1570-7, 2003. [PUBMED Abstract]
  36. Boccia R, Grunberg S, Franco-Gonzales E, et al.: Efficacy of oral palonosetron compared to intravenous palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: a phase 3 trial. Support Care Cancer 21 (5): 1453-60, 2013. [PUBMED Abstract]
  37. Hickok JT, Roscoe JA, Morrow GR, et al.: 5-Hydroxytryptamine-receptor antagonists versus prochlorperazine for control of delayed nausea caused by doxorubicin: a URCC CCOP randomised controlled trial. Lancet Oncol 6 (10): 765-72, 2005. [PUBMED Abstract]
  38. Kris MG: Why do we need another antiemetic? Just ask. J Clin Oncol 21 (22): 4077-80, 2003. [PUBMED Abstract]
  39. Tyers MB: Pharmacology and preclinical antiemetic properties of ondansetron. Semin Oncol 19 (4 Suppl 10): 1-8, 1992. [PUBMED Abstract]
  40. Kaasa S, Kvaløy S, Dicato MA, et al.: A comparison of ondansetron with metoclopramide in the prophylaxis of chemotherapy-induced nausea and vomiting: a randomized, double-blind study. International Emesis Study Group. Eur J Cancer 26 (3): 311-4, 1990. [PUBMED Abstract]
  41. Hainsworth J, Harvey W, Pendergrass K, et al.: A single-blind comparison of intravenous ondansetron, a selective serotonin antagonist, with intravenous metoclopramide in the prevention of nausea and vomiting associated with high-dose cisplatin chemotherapy. J Clin Oncol 9 (5): 721-8, 1991. [PUBMED Abstract]
  42. De Mulder PH, Seynaeve C, Vermorken JB, et al.: Ondansetron compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting. A multicenter, randomized, double-blind, crossover study. Ann Intern Med 113 (11): 834-40, 1990. [PUBMED Abstract]
  43. Marty M, Pouillart P, Scholl S, et al.: Comparison of the 5-hydroxytryptamine3 (serotonin) antagonist ondansetron (GR 38032F) with high-dose metoclopramide in the control of cisplatin-induced emesis. N Engl J Med 322 (12): 816-21, 1990. [PUBMED Abstract]
  44. Hesketh PJ: Comparative trials of ondansetron versus metoclopramide in the prevention of acute cisplatin-induced emesis. Semin Oncol 19 (4 Suppl 10): 33-40, 1992. [PUBMED Abstract]
  45. Beck TM, Hesketh PJ, Madajewicz S, et al.: Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting. J Clin Oncol 10 (12): 1969-75, 1992. [PUBMED Abstract]
  46. Hasler SB, Hirt A, Ridolfi Luethy A, et al.: Safety of ondansetron loading doses in children with cancer. Support Care Cancer 16 (5): 469-75, 2008. [PUBMED Abstract]
  47. U.S. Food and Drug Administration: FDA Drug Safety Communication: New information regarding QT prolongation with ondansetron (Zofran). Silver Spring, Md: U.S. Food and Drug Administration, 2012. Available online. Last accessed June 25, 2015.
  48. Finn AL: Toxicity and side effects of ondansetron. Semin Oncol 19 (4 Suppl 10): 53-60, 1992. [PUBMED Abstract]
  49. Coates AS, Childs A, Cox K, et al.: Severe vascular adverse effects with thrombocytopenia and renal failure following emetogenic chemotherapy and ondansetron. Ann Oncol 3 (9): 719-22, 1992. [PUBMED Abstract]
  50. Ruff P, Paska W, Goedhals L, et al.: Ondansetron compared with granisetron in the prophylaxis of cisplatin-induced acute emesis: a multicentre double-blind, randomised, parallel-group study. The Ondansetron and Granisetron Emesis Study Group. Oncology 51 (1): 113-8, 1994 Jan-Feb. [PUBMED Abstract]
  51. Jantunen IT, Muhonen TT, Kataja VV, et al.: 5-HT3 receptor antagonists in the prophylaxis of acute vomiting induced by moderately emetogenic chemotherapy--a randomised study. Eur J Cancer 29A (12): 1669-72, 1993. [PUBMED Abstract]
  52. Hesketh PJ, Grunberg SM, Gralla RJ, et al.: The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin--the Aprepitant Protocol 052 Study Group. J Clin Oncol 21 (22): 4112-9, 2003. [PUBMED Abstract]
  53. Gebbia V, Cannata G, Testa A, et al.: Ondansetron versus granisetron in the prevention of chemotherapy-induced nausea and vomiting. Results of a prospective randomized trial. Cancer 74 (7): 1945-52, 1994. [PUBMED Abstract]
  54. Boccia RV, Gordan LN, Clark G, et al.: Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study. Support Care Cancer 19 (10): 1609-17, 2011. [PUBMED Abstract]
  55. U.S. Food and Drug Administration: FDA Drug Safety Communication: Abnormal heart rhythms associated with use of Anzemet (dolasetron mesylate). Silver Spring, Md: U.S. Food and Drug Administration, 2010. Available online. Last accessed July 2, 2015.
  56. Fauser AA, Duclos B, Chemaissani A, et al.: Therapeutic equivalence of single oral doses of dolasetron mesilate and multiple doses of ondansetron for the prevention of emesis after moderately emetogenic chemotherapy. European Dolasetron Comparative Study Group. Eur J Cancer 32A (9): 1523-9, 1996. [PUBMED Abstract]
  57. Eisenberg P, MacKintosh FR, Ritch P, et al.: Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: a dose-ranging clinical study. Ann Oncol 15 (2): 330-7, 2004. [PUBMED Abstract]
  58. Tricco AC, Soobiah C, Antony J, et al.: Safety of serotonin (5-HT3) receptor antagonists in patients undergoing surgery and chemotherapy: protocol for a systematic review and network meta-analysis. Syst Rev 2: 46, 2013. [PUBMED Abstract]
  59. Faria C, Li X, Nagl N, et al.: Outcomes Associated with 5-HT3-RA Therapy Selection in Patients with Chemotherapy-Induced Nausea and Vomiting: A Retrospective Claims Analysis. Am Health Drug Benefits 7 (1): 50-8, 2014. [PUBMED Abstract]
  60. Schwartzberg L, Barbour SY, Morrow GR, et al.: Pooled analysis of phase III clinical studies of palonosetron versus ondansetron, dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and vomiting (CINV). Support Care Cancer 22 (2): 469-77, 2014. [PUBMED Abstract]
  61. Affronti ML, Bubalo J: Palonosetron in the management of chemotherapy-induced nausea and vomiting in patients receiving multiple-day chemotherapy. Cancer Manag Res 6: 329-37, 2014. [PUBMED Abstract]
  62. Navari RM: Palonosetron for the prevention of chemotherapy-induced nausea and vomiting: approval and efficacy. Cancer Manag Res 1: 167-76, 2009. [PUBMED Abstract]
  63. Aapro MS, Grunberg SM, Manikhas GM, et al.: A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol 17 (9): 1441-9, 2006. [PUBMED Abstract]
  64. Navari RM: Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist. Future Oncol 2 (5): 591-602, 2006. [PUBMED Abstract]
  65. Humphreys S, Pellissier J, Jones A: Cost-effectiveness of an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer in the UK. Cancer Manag Res 5: 215-24, 2013. [PUBMED Abstract]
  66. Warr DG, Street JC, Carides AD: Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of phase 3 trial of aprepitant in patients receiving adriamycin-cyclophosphamide-based chemotherapy. Support Care Cancer 19 (6): 807-13, 2011. [PUBMED Abstract]
  67. Hesketh PJ, Aapro M, Street JC, et al.: Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of two phase III trials of aprepitant in patients receiving cisplatin-based chemotherapy. Support Care Cancer 18 (9): 1171-7, 2010. [PUBMED Abstract]
  68. Hu W, Fang J, Nie J, et al.: Addition of aprepitant improves protection against cisplatin-induced emesis when a conventional anti-emetic regimen fails. Cancer Chemother Pharmacol 73 (6): 1129-36, 2014. [PUBMED Abstract]
  69. Van Belle S, Lichinitser MR, Navari RM, et al.: Prevention of cisplatin-induced acute and delayed emesis by the selective neurokinin-1 antagonists, L-758,298 and MK-869. Cancer 94 (11): 3032-41, 2002. [PUBMED Abstract]
  70. Campos D, Pereira JR, Reinhardt RR, et al.: Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone. J Clin Oncol 19 (6): 1759-67, 2001. [PUBMED Abstract]
  71. Chawla SP, Grunberg SM, Gralla RJ, et al.: Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Cancer 97 (9): 2290-300, 2003. [PUBMED Abstract]
  72. de Wit R, Herrstedt J, Rapoport B, et al.: Addition of the oral NK1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy. J Clin Oncol 21 (22): 4105-11, 2003. [PUBMED Abstract]
  73. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, et al.: Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer 97 (12): 3090-8, 2003. [PUBMED Abstract]
  74. Schmoll HJ, Aapro MS, Poli-Bigelli S, et al.: Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol 17 (6): 1000-6, 2006. [PUBMED Abstract]
  75. Warr DG, Hesketh PJ, Gralla RJ, et al.: Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 23 (12): 2822-30, 2005. [PUBMED Abstract]
  76. Grote T, Hajdenberg J, Cartmell A, et al.: Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone, and aprepitant. J Support Oncol 4 (8): 403-8, 2006. [PUBMED Abstract]
  77. Rapoport BL, Jordan K, Boice JA, et al.: Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: a randomized, double-blind study. Support Care Cancer 18 (4): 423-31, 2010. [PUBMED Abstract]
  78. Albany C, Brames MJ, Fausel C, et al.: Randomized, double-blind, placebo-controlled, phase III cross-over study evaluating the oral neurokinin-1 antagonist aprepitant in combination with a 5HT3 receptor antagonist and dexamethasone in patients with germ cell tumors receiving 5-day cisplatin combination chemotherapy regimens: a hoosier oncology group study. J Clin Oncol 30 (32): 3998-4003, 2012. [PUBMED Abstract]
  79. Aapro MS, Schmoll HJ, Jahn F, et al.: Review of the efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in a range of tumor types. Cancer Treat Rev 39 (1): 113-7, 2013. [PUBMED Abstract]
  80. Grunberg S, Chua D, Maru A, et al.: Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE. J Clin Oncol 29 (11): 1495-501, 2011. [PUBMED Abstract]
  81. Navari RM: Fosaprepitant: a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Expert Rev Anticancer Ther 8 (11): 1733-42, 2008. [PUBMED Abstract]
  82. Hesketh PJ, Rossi G, Rizzi G, et al.: Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose-ranging pivotal study. Ann Oncol 25 (7): 1340-6, 2014. [PUBMED Abstract]
  83. Aapro M, Rugo H, Rossi G, et al.: A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol 25 (7): 1328-33, 2014. [PUBMED Abstract]
  84. Bishop JF, Matthews JP, Wolf MM, et al.: A randomised trial of dexamethasone, lorazepam and prochlorperazine for emesis in patients receiving chemotherapy. Eur J Cancer 28 (1): 47-50, 1992. [PUBMED Abstract]
  85. Chiara S, Campora E, Lionetto R, et al.: Methylprednisolone for the control of CMF-induced emesis. Am J Clin Oncol 10 (3): 264-7, 1987. [PUBMED Abstract]
  86. Parry H, Martin K: Single-dose i.v. dexamethasone--an effective anti-emetic in cancer chemotherapy. Cancer Chemother Pharmacol 28 (3): 231-2, 1991. [PUBMED Abstract]
  87. Cassileth PA, Lusk EJ, Torri S, et al.: Antiemetic efficacy of high-dose dexamethasone in induction therapy in acute nonlymphocytic leukemia. Ann Intern Med 100 (5): 701-2, 1984. [PUBMED Abstract]
  88. Aapro MS, Plezia PM, Alberts DS, et al.: Double-blind crossover study of the antiemetic efficacy of high-dose dexamethasone versus high-dose metoclopramide. J Clin Oncol 2 (5): 466-71, 1984. [PUBMED Abstract]
  89. Schallier D, Van Belle S, De Greve J, et al.: Methylprednisolone as an antiemetic drug. A randomised double blind study. Cancer Chemother Pharmacol 14 (3): 235-7, 1985. [PUBMED Abstract]
  90. Kris MG, Gralla RJ, Clark RA, et al.: Consecutive dose-finding trials adding lorazepam to the combination of metoclopramide plus dexamethasone: improved subjective effectiveness over the combination of diphenhydramine plus metoclopramide plus dexamethasone. Cancer Treat Rep 69 (11): 1257-62, 1985. [PUBMED Abstract]
  91. Greenberg DB, Surman OS, Clarke J, et al.: Alprazolam for phobic nausea and vomiting related to cancer chemotherapy. Cancer Treat Rep 71 (5): 549-50, 1987. [PUBMED Abstract]
  92. Hockenberry-Eaton M, Benner A: Patterns of nausea and vomiting in children: nursing assessment and intervention. Oncol Nurs Forum 17 (4): 575-84, 1990 Jul-Aug. [PUBMED Abstract]
  93. Münstedt K, Borces D, Bohlmann MK, et al.: Glucocorticoid administration in antiemetic therapy: is it safe? Cancer 101 (7): 1696-702, 2004. [PUBMED Abstract]
  94. Roila F, Tonato M, Cognetti F, et al.: Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone. J Clin Oncol 9 (4): 675-8, 1991. [PUBMED Abstract]
  95. Zaglama NE, Rosenblum SL, Sartiano GP, et al.: Single, high-dose intravenous dexamethasone as an antiemetic in cancer chemotherapy. Oncology 43 (1): 27-32, 1986. [PUBMED Abstract]
  96. Klygis LM: Dexamethasone-induced perineal irritation in head injury. Am J Emerg Med 10 (3): 268, 1992. [PUBMED Abstract]
  97. More on dexamethasone-induced perineal irritation. N Engl J Med 314 (25): 1643-4, 1986. [PUBMED Abstract]
  98. Baharav E, Harpaz D, Mittelman M, et al.: Dexamethasone-induced perineal irritation. N Engl J Med 314 (8): 515-6, 1986. [PUBMED Abstract]
  99. Triozzi PL, Goldstein D, Laszlo J: Contributions of benzodiazepines to cancer therapy. Cancer Invest 6 (1): 103-11, 1988. [PUBMED Abstract]
  100. Bishop JF, Olver IN, Wolf MM, et al.: Lorazepam: a randomized, double-blind, crossover study of a new antiemetic in patients receiving cytotoxic chemotherapy and prochlorperazine. J Clin Oncol 2 (6): 691-5, 1984. [PUBMED Abstract]
  101. Henry DW, Burwinkle JW, Klutman NE: Determination of sedative and amnestic doses of lorazepam in children. Clin Pharm 10 (8): 625-9, 1991. [PUBMED Abstract]
  102. van Hoff J, Olszewski D: Lorazepam for the control of chemotherapy-related nausea and vomiting in children. J Pediatr 113 (1 Pt 1): 146-9, 1988. [PUBMED Abstract]
  103. Potanovich LM, Pisters KM, Kris MG, et al.: Midazolam in patients receiving anticancer chemotherapy and antiemetics. J Pain Symptom Manage 8 (8): 519-24, 1993. [PUBMED Abstract]
  104. Olynyk JK, Cullen SR, Leahy MF: Midazolam: an effective antiemetic agent for cytotoxic chemotherapy. Med J Aust 150 (8): 466, 1989. [PUBMED Abstract]
  105. Mori K, Saito Y, Tominaga K: Antiemetic efficacy of alprazolam in the combination of metoclopramide plus methylprednisolone. Double-blind randomized crossover study in patients with cisplatin-induced emesis. Am J Clin Oncol 16 (4): 338-41, 1993. [PUBMED Abstract]
  106. Laszlo J, Clark RA, Hanson DC, et al.: Lorazepam in cancer patients treated with cisplatin: a drug having antiemetic, amnesic, and anxiolytic effects. J Clin Oncol 3 (6): 864-9, 1985. [PUBMED Abstract]
  107. Bymaster FP, Falcone JF, Bauzon D, et al.: Potent antagonism of 5-HT(3) and 5-HT(6) receptors by olanzapine. Eur J Pharmacol 430 (2-3): 341-9, 2001. [PUBMED Abstract]
  108. ZYPREXA (olanzapine): highlights of prescribing information. Indianapolis, Ind: Eli Lilly and Company, 2014. Available online. Last accessed June 25, 2015.
  109. Hocking CM, Kichenadasse G: Olanzapine for chemotherapy-induced nausea and vomiting: a systematic review. Support Care Cancer 22 (4): 1143-51, 2014. [PUBMED Abstract]
  110. Hale AS: Olanzapine. Br J Hosp Med 58 (9): 442-5, 1997 Nov 5-18. [PUBMED Abstract]
  111. Goldstein LE, Sporn J, Brown S, et al.: New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics 40 (5): 438-43, 1999 Sep-Oct. [PUBMED Abstract]
  112. Passik SD, Lundberg J, Kirsh KL, et al.: A pilot exploration of the antiemetic activity of olanzapine for the relief of nausea in patients with advanced cancer and pain. J Pain Symptom Manage 23 (6): 526-32, 2002. [PUBMED Abstract]
  113. Jackson WC, Tavernier L: Olanzapine for intractable nausea in palliative care patients. J Palliat Med 6 (2): 251-5, 2003. [PUBMED Abstract]
  114. Passik SD, Kirsh KL, Theobald DE, et al.: A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in cancer patients. J Pain Symptom Manage 25 (5): 485-8, 2003. [PUBMED Abstract]
  115. Passik SD, Navari RM, Jung SH, et al.: A phase I trial of olanzapine (Zyprexa) for the prevention of delayed emesis in cancer patients: a Hoosier Oncology Group study. Cancer Invest 22 (3): 383-8, 2004. [PUBMED Abstract]
  116. Navari RM, Einhorn LH, Passik SD, et al.: A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier Oncology Group study. Support Care Cancer 13 (7): 529-34, 2005. [PUBMED Abstract]
  117. Navari RM, Einhorn LH, Loehrer PJ Sr, et al.: A phase II trial of olanzapine, dexamethasone, and palonosetron for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier oncology group study. Support Care Cancer 15 (11): 1285-91, 2007. [PUBMED Abstract]
  118. Tan L, Liu J, Liu X, et al.: Clinical research of Olanzapine for prevention of chemotherapy-induced nausea and vomiting. J Exp Clin Cancer Res 28: 131, 2009. [PUBMED Abstract]
  119. Ben Amar M: Cannabinoids in medicine: A review of their therapeutic potential. J Ethnopharmacol 105 (1-2): 1-25, 2006. [PUBMED Abstract]
  120. Davis MP: Oral nabilone capsules in the treatment of chemotherapy-induced nausea and vomiting and pain. Expert Opin Investig Drugs 17 (1): 85-95, 2008. [PUBMED Abstract]
  121. Duran M, Pérez E, Abanades S, et al.: Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacol 70 (5): 656-63, 2010. [PUBMED Abstract]
  122. Machado Rocha FC, Stéfano SC, De Cássia Haiek R, et al.: Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care (Engl) 17 (5): 431-43, 2008. [PUBMED Abstract]
  123. Ahmedzai S, Carlyle DL, Calder IT, et al.: Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy. Br J Cancer 48 (5): 657-63, 1983. [PUBMED Abstract]
  124. Chan HS, Correia JA, MacLeod SM: Nabilone versus prochlorperazine for control of cancer chemotherapy-induced emesis in children: a double-blind, crossover trial. Pediatrics 79 (6): 946-52, 1987. [PUBMED Abstract]
  125. Johansson R, Kilkku P, Groenroos M: A double-blind, controlled trial of nabilone vs. prochlorperazine for refractory emesis induced by cancer chemotherapy. Cancer Treat Rev 9 (Suppl B): 25-33, 1982. [PUBMED Abstract]
  126. Niiranen A, Mattson K: A cross-over comparison of nabilone and prochlorperazine for emesis induced by cancer chemotherapy. Am J Clin Oncol 8 (4): 336-40, 1985. [PUBMED Abstract]
  127. Tramèr MR, Carroll D, Campbell FA, et al.: Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 323 (7303): 16-21, 2001. [PUBMED Abstract]
  128. Meiri E, Jhangiani H, Vredenburgh JJ, et al.: Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin 23 (3): 533-43, 2007. [PUBMED Abstract]
  129. Strasser F, Luftner D, Possinger K, et al.: Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol 24 (21): 3394-400, 2006. [PUBMED Abstract]
  130. Coffman KL: The debate about marijuana usage in transplant candidates: recent medical evidence on marijuana health effects. Curr Opin Organ Transplant 13 (2): 189-95, 2008. [PUBMED Abstract]
  131. Ryan JL, Heckler CE, Roscoe JA, et al.: Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients. Support Care Cancer 20 (7): 1479-89, 2012. [PUBMED Abstract]

Nonpharmacologic Management of Nausea and Vomiting (Emesis)

Nonpharmacologic strategies are also used to manage nausea and vomiting (N&V). These include the following:

Guided imagery, hypnosis, and systematic desensitization as means to progressive muscle relaxation have been the most frequently studied treatments for anticipatory N&V (ANV) and are the recommended treatments for this classically conditioned response. (Refer to the Treatment of ANV section of this summary for more information.)

Radiation Therapy

Correlates

Patients receiving radiation to the gastrointestinal (GI) tract or brain have the greatest potential for nausea and vomiting (N&V) as side effects. Because cells of the GI tract are dividing quickly, they are quite sensitive to radiation therapy. Radiation to the brain is believed to stimulate the brain’s vomiting center or chemoreceptor trigger zone. Similar to chemotherapy, radiation dose factors also play a role in determining the possible occurrence of N&V. In general, the higher the daily fractional dose and the greater the amount of tissue that is irradiated, the higher the potential for N&V. In addition, the larger the amount of GI tract irradiated (particularly for fields that include the small intestine and stomach), the higher the potential for N&V. Total-body irradiation before bone marrow transplant, for example, has a high probability of inducing N&V as acute side effects.

Prevalence

N&V from radiation may be acute and self-limiting, usually occurring 30 minutes to several hours after treatment. Patients report that symptoms improve on days that they are not being treated. There are also cumulative effects that may occur in patients receiving radiation therapy to the GI tract.[1]

Treatment

Complete control rates with 5-HT3 receptor antagonists for total-body irradiation vary from 50% to 90%.[2-4] The role of corticosteroids in combination with 5-HT3 receptor antagonists has not been studied.

References
  1. Kris MG, Hesketh PJ, Somerfield MR, et al.: American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 24 (18): 2932-47, 2006. [PUBMED Abstract]
  2. Spitzer TR, Grunberg SM, Dicato MA: Antiemetic strategies for high-dose chemoradiotherapy-induced nausea and vomiting. Support Care Cancer 6 (3): 233-6, 1998. [PUBMED Abstract]
  3. Prentice HG, Cunningham S, Gandhi L, et al.: Granisetron in the prevention of irradiation-induced emesis. Bone Marrow Transplant 15 (3): 445-8, 1995. [PUBMED Abstract]
  4. Schwella N, König V, Schwerdtfeger R, et al.: Ondansetron for efficient emesis control during total body irradiation. Bone Marrow Transplant 13 (2): 169-71, 1994. [PUBMED Abstract]

Changes to This Summary (07/17/2015)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary has been comprehensively reviewed and extensively revised.

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About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the pathophysiology and treatment of nausea and vomiting (emesis) (N&V). It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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The lead reviewers for Nausea and Vomiting are:

  • Joseph Bubalo, PharmD, BCPS, BCOP (Oregon Health and Science University Hospital)
  • Lillian M. Nail, PhD, RN, FAAN, CNS (Oregon Health & Science University Cancer Institute)
  • Eric E. Prommer, MD (UCLA School of Medicine)
  • Eric Sandler, MD (Nemours Children's Clinic)

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