National Cancer Institute National Cancer Institute
U.S. National Institutes of Health National Cancer Institute
Send to Printer
Non-Small Cell Lung Cancer Treatment (PDQ®)     
Last Modified: 07/10/2009
Health Professional Version
Stage IV Non-Small Cell Lung Cancer

Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence 1 for more information.)

Stage IV non-small cell lung cancer (NSCLC) is defined by the following clinical stage grouping:

  • Any T, any N, M1

Forty percent of patients with newly diagnosed NSCLC have stage IV disease. Randomized controlled trials of patients with stage IV disease and stage IIIB disease with malignant pleural effusions and good performance status (PS) have shown that cisplatin-based chemotherapy improves survival and palliates disease-related symptoms.[Level of evidence: 1iiA] Patients with nonsquamous cell histology, good PS, no history of hemoptysis or other bleeding or recent history of cardiovascular events may benefit from the addition of bevacizumab to paclitaxel carboplatin. The role of chemotherapy in patients with poor PS was less certain. Second-line chemotherapy with docetaxel, pemetrexed, or erlotinib also improves survival patients with good PS.[1][Level of evidence: 1iiA]

Several randomized trials have evaluated various drugs combined with either cisplatin or carboplatinum in previously untreated patients with advanced NSCLC. Based on meta-analyses of the trials the following conclusions can be drawn:

  1. Platinum combinations with vinorelbine, paclitaxel, docetaxel, gemcitabine, irinotecan, and pemetrexed yield similar improvements in survival. Types and frequencies of toxic effects differ, and these may determine the preferred regimen for an individual patient.
  2. Cisplatin and carboplatinum yield similar improvements in outcome, although some but not all trials and meta-analyses of trials suggest that outcomes with cisplatin may be superior, although with a higher risk of certain toxicities such as nausea and vomiting.
  3. Nonplatinum combinations offer no advantage to platinum-based chemotherapy, and some studies demonstrate inferiority.
  4. Three-drug combinations of the commonly used chemotherapy drugs do not result in superior survival and are more toxic than two-drug combinations.
  5. Certain three-drug combinations that add so-called targeted agents may result in superior survival.

In a randomized study of 878 patients with recurrent or advanced stage IIIB or stage IV NSCLC, 444 received paclitaxel and carboplatin alone, and 434 patients received paclitaxel and carboplatin plus bevacizumab.[2] Chemotherapy was administered every 3 weeks for six cycles, and bevacizumab was administered every 3 weeks until disease progression was evident or toxic effects were intolerable. Patients with squamous cell tumors, brain metastases, clinically significant hemoptysis, or inadequate organ function or PS (ECOG PS >1) were excluded. The median survival was 12.3 months in the group assigned to chemotherapy plus bevacizumab, as compared with 10.3 months in the chemotherapy-alone group (hazard ratio [HR] for death, 0.79; P = .003). The median progression-free survival in the two groups was 6.2 months and 4.5 months, respectively (HR for disease progression, 0.66; P < .001), with corresponding response rates of 35% and 15% (P < .001). Rates of clinically significant bleeding were 4.4% and 0.7%, respectively (P < .001). There were 15 treatment-related deaths in the chemotherapy-plus-bevacizumab group, including five from pulmonary hemorrhage. For this subgroup of patients with NSCLC, the addition of bevacizumab to paclitaxel and carboplatin may provide survival benefit.[2][Level of evidence: 1iiA]

The type and number of chemotherapy drugs to be used for the treatment of patients with advanced NSCLC has been extensively evaluated in randomized controlled trials and meta-analyses. The Cochrane Collaboration group reviewed data from all randomized controlled trials published between January 1980 and June 2006, comparing a doublet regimen with a single-agent regimen or comparing a triplet regimen with a doublet regimen in patients with advanced NSCLC.[3] Sixty-five trials (13,601 patients) were identified. In the trials comparing a doublet regimen with a single-agent regimen, a significant increase was observed in tumor response (OR = 0.42; 95% confidence interval [CI], 0.37– 0.47, P < .001) and 1-year survival (OR = 0.80; 95% CI, 0.70–0.91, P < .001) in favor of the doublet regimen. The absolute benefit in 1-year survival was 5%, which corresponds to an increase in 1-year survival from 30% with a single-agent regimen to 35% with a doublet regimen. The rates of grades 3 and 4 toxic effects caused by doublet regimens were statistically increased compared with rates following single-agent therapy, with ORs ranging from 1.2 to 6.2. There was no increase in infection rates in doublet regimens. There was no increase in 1-year survival (OR = 1.01; 95% CI, 0.85–1.21; P = .88) for triplet regimens versus doublet regimens. The median survival ratio was 1.00 (95% CI, 0.94–1.06, P = .97).

Several meta-analyses have evaluated whether cisplatin or carboplatin regimens are superior with variable results.[4-6] One meta-analysis reported individual patient data for 2,968 patients entered in nine randomized trials.[4] The objective response rate was higher for patients treated with cisplatin than for patients treated with carboplatin (30% vs. 24%, respectively; OR = 1.37; 95% CI, 1.16–1.61; P < .001). Carboplatin treatment was associated with a nonstatistically significant increase in the hazard of mortality relative to treatment with cisplatin (HR = 1.07; 95% CI, 0.99–1.15; P = .100). In patients with nonsquamous tumors and those treated with third-generation chemotherapy, carboplatin-based chemotherapy was associated with a statistically significant increase in mortality (HR = 1.12; 95% CI, 1.01–1.23 and HR = 1.11; 95% CI, 1.01–1.21, respectively). Treatment-related toxic effects were also assessed in the meta-analysis. More thrombocytopenia was seen with carboplatin than with cisplatin (12% vs. 6%; OR = 2.27; 95% CI, 1.71–3.01; P < .001), while cisplatin caused more nausea and vomiting (8% vs. 18%; OR = 0.42; 95% CI, 0.33–0.53; P < .001) and renal toxic effects (0.5% vs. 1.5%; OR = 0.37; 95% CI, 0.15–0.88; P = .018). The authors concluded that treatment with cisplatin was not associated with a substantial increase in the overall risk of severe toxic effects. This comprehensive individual-patient meta-analysis is consistent with the conclusions of other meta-analyses, which were based on essentially the same clinical trials but which used only published data.

Three literature-based meta-analyses have trials comparing platinum to nonplatinum combinations.[7-9] The first meta-analysis identified 37 assessable trials that included 7,633 patients.[7] A 62% increase in the OR for response was attributable to platinum-based therapy (OR = 1.62; 95% CI, 1.46–1.8; P < .001). The 1-year survival rate was increased by 5% with platinum-based regimens (34% vs. 29%; OR = 1.21; 95% CI, 1.09–1.35; P = .003). No statistically significant increase in 1-year survival was found when platinum therapies were compared to third-generation-based combination regimens (OR = 1.11; 95% CI, 0.96–1.28; P = .17). The toxic effects of platinum-based regimens was significantly higher for hematologic toxic effects, nephrotoxic effects, and nausea and vomiting, but not for neurologic toxic effects, febrile neutropenia rate, or toxic death rate. These results are consistent with the second literature-based meta-analysis.

The second meta-analysis identified 17 trials that included 4,920 patients.[8] The use of platinum-based doublet regimens was associated with a slightly higher survival at 1 year (RR = 1.08; 95% CI, 1.01–1.16, P = .03), better partial response (RR = 1.11, 95% CI, 1.02–1.21; P = .02), with a higher risk of anemia, nausea, and neurologic toxic effects. However, in subanalyses, cisplatin-based doublet regimens improved survival at 1 year (RR = 1.16; 95% CI, 1.06–1.27; P = .001), complete response (RR = 2.29; 95% CI, 1.08–4.88; P = .03), partial response (RR = 1.19; 95% CI, 1.07–1.32; P = .002) with an increased risk of anemia, neutropenia, neurologic toxic effects, and nausea. Conversely, carboplatin-based doublet regimens did not increase survival at 1 year (RR = 0.95; 95% CI, 0.85–1.07; P = .43).

The third meta-analysis of phase III trials randomizing platinum-based versus nonplatinum combinations as first-line chemotherapy identified 14 trials.[9] Experimental arms were gemcitabine and vinorelbine (n = 4), gemcitabine and taxane (n = 7), gemcitabine and epirubicin (n = 1), paclitaxel and vinorelbine (n = 1), and gemcitabine and ifosfamide (n = 1). This meta-analysis was limited to the set of 11 phase III studies that used a platinum-based doublet (2,298 and 2,304 patients in platinum-based and nonplatinum arms, respectively). Patients treated with a platinum-based regimen benefited from a statically significant reduction in the risk of death at 1 year (odds ratio [OR] = 0.88; 95% CI, 0.78–0.99; P = .044) and a lower risk of being refractory to chemotherapy (OR = 0.87; 0.73–0.99; P = .049). Forty-four (1.9%) and 29 (1.3%) toxic-related deaths were reported for platinum-based and nonplatinum regimens, respectively (OR = 1.53; 0.96–2.49; P = 0.08). An increased risk of grade 3–4 gastrointestinal and hematological toxic effects for patients receiving platinum-based chemotherapy was statistically demonstrated. There was no statistically significant increase in risk of febrile neutropenia (OR=1.23; 0.94–1.60; P = .063).

Among the active combinations, definitive recommendations regarding drug dose and schedule cannot be made. However, there has been one meta-analysis of seven trials that included 2,867 patients to assess the benefit of docetaxel versus vinorelbine.[10] Docetaxel was administered with a platinum agent in three trials, with gemcitabine in two trials, or as monotherapy in two trials. Vinca alkaloid (vinorelbine in six trials and vindesine in one trial) was administered with cisplatin in six trials or alone in one trial. The pooled estimate for OS showed an 11% improvement in favor of docetaxel (HR = 0.89; 95% CI, 0.82–0.96; P = .004). Sensitivity analyses considering only vinorelbine as a comparator or only the doublet regimens showed similar improvements. Grade 3–4 neutropenia and grade 3–4 serious adverse events were less frequent with docetaxel-based regimens versus vinca alkaloid-based regimens (OR = 0.59; 95% CI, 0.38–0.89; P = .013 and OR = 0.68; 95% CI, 0.55–0.84; P < .001, respectively). There have been two randomized trials comparing weekly versus every 3 weeks' dosing of paclitaxel carboplatin, which reported no significant difference in efficacy and better tolerability for weekly administration.[11,12] Although meta-analyses of randomized controlled trials suggest that cisplatin combinations may be superior to carboplatin or nonplatinum combinations, the clinical relevance of the differences in efficacy must be balanced against the anticipated tolerability, logistics of administration, and familiarity of the medical staff for treatment decisions for individual patients.

A large noninferiority, phase III, randomized study compared the overall survival in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and a PS of 0 to 1.[13] Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. OS for cisplatin and pemetrexed was noninferior to cisplatin and gemcitabine (median survival, 10.3 mo vs. 10.3 mo, respectively; HR = 0.94; 95% CI, 0.84–1.05). OS was statistically superior for cisplatin and pemetrexed versus cisplatin and gemcitabine in patients with adenocarcinoma (n = 847; 12.6 mo vs. 10.9 mo, respectively) and large-cell carcinoma histology (n = 153; 10.4 mo vs. 6.7 mo, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin and gemcitabine versus cisplatin and pemetrexed (n = 473; 10.8 mo vs. 9.4 mo, respectively). For cisplatin and pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P ≤ .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common. This study suggests that cisplatin and pemtrexed is another alternative doublet for first-line chemotherapy of advanced NSCLC and also suggests that there may be differences in outcome depending on histology.

Platinum-containing combination chemotherapy regimens provide clinical benefit when compared with supportive care or single-agent therapy; however, such treatment may be contraindicated in some older patients because of the age-related reduction in the functional reserve of many organs and/or comorbid conditions. Approximately two-thirds of patients with NSCLC are 65 years or older and approximately 40% are 70 years or older.[14] Surveillance, Epidemiology, and End Results (SEER) data suggest that the percentage of patients who are older than 70 years is closer to 50%. A review of the SEER Medicare data from 1994 to 1999 found a much lower rate of chemotherapy use than expected for the overall population.[15] It also suggested that the elderly may have more comorbidities or a higher rate of functional compromise that would make study participation difficult, if not contraindicated, and lack of clinical trial data may influence decisions to treat individual patients with standard chemotherapy.

Single-agent chemotherapy and combination chemotherapy clearly benefit at least some elderly patients. In the Elderly Lung Cancer Vinorelbine Italian Study, 154 patients who were older than 70 years were randomized to vinorelbine or supportive care.[16] Patients who were treated with vinorelbine had a 1-year survival rate of 32%, compared with 14% for those who were treated with supportive care alone. Quality-of-life parameters were also significantly improved in the chemotherapy arm, and toxic effects were acceptable. A more recent trial from Japan compared single-agent docetaxel with vinorelbine in 180 elderly patients with good PS.[17] Response rates and progression-free survival were significantly better with docetaxel (22% vs. 10%; 5.4 months vs. 3.1 months, respectively), whereas median and 1-year survival rates did not reach statistical significance (14.3 months vs. 9.9 months; 59% vs. 37%, respectively). Retrospective data analyzing and comparing younger (<70 years old) with older (≥70 years old) patients who participated in large, randomized trials of doublet combinations have also shown that elderly patients may derive the same survival benefit although with a higher risk of toxic effects in the bone marrow.[18-23] Evidence supports that elderly patients with good PS and limited comorbidity may benefit from combination chemotherapy.

In summary, age alone should not dictate treatment-related decisions in patients with advanced NSCLC. Elderly patients with a good PS enjoy longer survival and a better quality of life when treated with chemotherapy compared with supportive care alone. Caution should be exercised when extrapolating data for elderly patients (70–79 years old) to patients who are 80 years or older because only a very small number of patients greater than 80 years of age have been enrolled on clinical trials, and the benefit in this group is uncertain.[18,19]

PS is among the most important prognostic factors for survival of patients with NSCLC.[24] The benefit of therapy for this group of patients has been evaluated through retrospective analyses as well as through prospective clinical trials. The Cancer and Leukemia Group B-9730 trial, CALGB-9730 2, which compared carboplatin and paclitaxel to paclitaxel, enrolled 99 patients with a PS of 2 (18% of the study's population). When compared with patients with a PS of 0 to 1, who had a median survival of 8.8 months and a 1-year survival of 38%, the corresponding figures for patients with a performance status of 2 were 3.0 months and 14%, respectively; this demonstrates the poor prognosis conferred by a lower PS. These differences were statistically significant. When patients with a PS of 2 were analyzed by treatment arm, those who received combination chemotherapy had a significantly higher response rate (24% vs. 10%), longer median survival (4.7 mo vs. 2.4 mo), and superior 1-year survival (18% vs. 10%) compared with those who were treated with single-agent paclitaxel.[22]

A subset analysis of 68 patients with a PS of 2 from a trial that randomly assigned more than 1,200 patients to four platinum-based regimens has been published. Despite a high incidence of adverse events, including five deaths, the final analysis showed that the overall toxic effects experienced by patients with a PS of 2 was not significantly different from that experienced by patients with a PS of 0 to 1. Efficacy analysis demonstrated an overall response rate of 14%, median survival time of 4.1 months, and a 1-year survival rate of 19%; all were substantially inferior to the patients with PS of 0 to 1. A phase II randomized trial (ECOG-1599 3) of attenuated dosages of cisplatin plus gemcitabine and carboplatin plus paclitaxel included 102 patients with a PS of 2.[25] Response rates were 25% and 16%, median survival times were 6.8 months and 6.1 months, and 1-year survival rates were 25% and 19%, respectively. None of these differences was statistically significant, but the survival figures were longer than expected on the basis of historical controls. Results from two trials suggest that patients with a PS of 2 may experience symptom improvement.[26,27]

The results support further evaluation of chemotherapeutic approaches for both metastatic and locally advanced NSCLC; however, the efficacy of current platinum-based chemotherapy combinations is such that no specific regimen can be regarded as standard therapy. Outside of a clinical trial setting, chemotherapy should be given only to patients with good PS and evaluable tumor lesions, who desire such treatment after being fully informed of its anticipated risks and limited benefits.

Radiation therapy may be effective in palliating symptomatic patients with local involvement, such as tracheal, esophageal, or bronchial compression; pain; vocal cord paralysis; hemoptysis; or superior vena cava syndrome. (Refer to the PDQ summary on Cardiopulmonary Syndromes 4 for more information). In some cases, endobronchial laser therapy and/or brachytherapy has been used to alleviate proximal obstructing lesions.[28] A systematic review identified six randomized trials of high-dose rate brachytherapy (HDREB) alone or with external-beam radiation therapy (EBRT) or laser therapy.[29] Better overall symptom palliation and fewer retreatments were required in previously untreated patients using EBRT alone.[29][Level of evidence: 1iiC] HDREB did provide palliation of symptomatic patients with recurrent endobronchial obstruction previously treated by EBRT, providing it is technically feasible. Although EBRT is frequently proscribed for symptom palliation, there is no consensus on which fractionation scheme should be used. Although different multifraction regimens appear to provide similar symptom relief, [30-35] single-fraction radiation may be insufficient for symptom relief compared with hypofractionated or standard regimens, as evidenced in the NCIC-CTG-SC15 5 trial.[36][Level of evidence: 1iiC] Evidence is available of a modest increase in survival in patients with a better PS given high-dose radiation therapy.[37,38][Level of evidence: 1iiA] In closely observed asymptomatic patients, treatment may often be appropriately deferred until symptoms or signs of a progressive tumor develop.

Treatment options:

  1. EBRT, primarily for palliative relief of local symptomatic tumor growth.[36,37,39]

  2. Doublet of chemotherapy with platinum (cisplatin or carboplatin) and paclitaxel, gemcitabine, docetaxel, vinorelbine, irinotecan, and pemetrexed.

  3. Paclitaxel, carboplatin, and bevacizumab for patients with non-squamous histology, no brain metastases, or no hemoptysis.

  4. Clinical trials evaluating the role of new chemotherapy regimens and other systemic agents.

  5. Endobronchial laser therapy and/or brachytherapy for obstructing lesions.[28]

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV non-small cell lung cancer 6. The list of clinical 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 7.

References

  1. Weick JK, Crowley J, Natale RB, et al.: A randomized trial of five cisplatin-containing treatments in patients with metastatic non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol 9 (7): 1157-62, 1991.  [PUBMED Abstract]

  2. Sandler A, Gray R, Perry MC, et al.: Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355 (24): 2542-50, 2006.  [PUBMED Abstract]

  3. Delbaldo C, Michiels S, Rolland E, et al.: Second or third additional chemotherapy drug for non-small cell lung cancer in patients with advanced disease. Cochrane Database Syst Rev (4): CD004569, 2007.  [PUBMED Abstract]

  4. Ardizzoni A, Boni L, Tiseo M, et al.: Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis. J Natl Cancer Inst 99 (11): 847-57, 2007.  [PUBMED Abstract]

  5. Jiang J, Liang X, Zhou X, et al.: A meta-analysis of randomized controlled trials comparing carboplatin-based to cisplatin-based chemotherapy in advanced non-small cell lung cancer. Lung Cancer 57 (3): 348-58, 2007.  [PUBMED Abstract]

  6. Hotta K, Matsuo K, Ueoka H, et al.: Meta-analysis of randomized clinical trials comparing Cisplatin to Carboplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol 22 (19): 3852-9, 2004.  [PUBMED Abstract]

  7. D'Addario G, Pintilie M, Leighl NB, et al.: Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a meta-analysis of the published literature. J Clin Oncol 23 (13): 2926-36, 2005.  [PUBMED Abstract]

  8. Rajeswaran A, Trojan A, Burnand B, et al.: Efficacy and side effects of cisplatin- and carboplatin-based doublet chemotherapeutic regimens versus non-platinum-based doublet chemotherapeutic regimens as first line treatment of metastatic non-small cell lung carcinoma: a systematic review of randomized controlled trials. Lung Cancer 59 (1): 1-11, 2008.  [PUBMED Abstract]

  9. Pujol JL, Barlesi F, Daurès JP: Should chemotherapy combinations for advanced non-small cell lung cancer be platinum-based? A meta-analysis of phase III randomized trials. Lung Cancer 51 (3): 335-45, 2006.  [PUBMED Abstract]

  10. Douillard JY, Laporte S, Fossella F, et al.: Comparison of docetaxel- and vinca alkaloid-based chemotherapy in the first-line treatment of advanced non-small cell lung cancer: a meta-analysis of seven randomized clinical trials. J Thorac Oncol 2 (10): 939-46, 2007.  [PUBMED Abstract]

  11. Belani CP, Ramalingam S, Perry MC, et al.: Randomized, phase III study of weekly paclitaxel in combination with carboplatin versus standard every-3-weeks administration of carboplatin and paclitaxel for patients with previously untreated advanced non-small-cell lung cancer. J Clin Oncol 26 (3): 468-73, 2008.  [PUBMED Abstract]

  12. Schuette W, Blankenburg T, Guschall W, et al.: Multicenter randomized trial for stage IIIB/IV non-small-cell lung cancer using every-3-week versus weekly paclitaxel/carboplatin. Clin Lung Cancer 7 (5): 338-43, 2006.  [PUBMED Abstract]

  13. Scagliotti GV, Parikh P, von Pawel J, et al.: Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 26 (21): 3543-51, 2008.  [PUBMED Abstract]

  14. Ries LA: Influence of extent of disease, histology, and demographic factors on lung cancer survival in the SEER population-based data. Semin Surg Oncol 10 (1): 21-30, 1994 Jan-Feb.  [PUBMED Abstract]

  15. Ramsey SD, Howlader N, Etzioni RD, et al.: Chemotherapy use, outcomes, and costs for older persons with advanced non-small-cell lung cancer: evidence from surveillance, epidemiology and end results-Medicare. J Clin Oncol 22 (24): 4971-8, 2004.  [PUBMED Abstract]

  16. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. The Elderly Lung Cancer Vinorelbine Italian Study Group. J Natl Cancer Inst 91 (1): 66-72, 1999.  [PUBMED Abstract]

  17. Takeda K, Kudoh S, Nakagawa K, et al.: Randomized phase III study of docetaxel (D) versus vinorelbine (V) for elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): Results of a West Japan Thoracic Oncology Group trial (WJTOG9904). [Abstract] J Clin Oncol 23 (Suppl 16): A-7009, 2005. 

  18. Langer CJ, Vangel M, Schiller J, et al.: Age-specific subanalysis of ECOG 1594: fit elderly patients (70-80 YRS) with NSCLC do as well as younger pts (<70). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2571, 2003. 

  19. Langer CJ, Manola J, Bernardo P, et al.: Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: implications of Eastern Cooperative Oncology Group 5592, a randomized trial. J Natl Cancer Inst 94 (3): 173-81, 2002.  [PUBMED Abstract]

  20. Schiller JH, Harrington D, Belani CP, et al.: Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346 (2): 92-8, 2002.  [PUBMED Abstract]

  21. Belani CP, Fossella F: Elderly subgroup analysis of a randomized phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for first-line treatment of advanced nonsmall cell lung carcinoma (TAX 326). Cancer 104 (12): 2766-74, 2005.  [PUBMED Abstract]

  22. Lilenbaum RC, Herndon JE 2nd, List MA, et al.: Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730). J Clin Oncol 23 (1): 190-6, 2005.  [PUBMED Abstract]

  23. Hensing TA, Peterman AH, Schell MJ, et al.: The impact of age on toxicity, response rate, quality of life, and survival in patients with advanced, Stage IIIB or IV nonsmall cell lung carcinoma treated with carboplatin and paclitaxel. Cancer 98 (4): 779-88, 2003.  [PUBMED Abstract]

  24. Sweeney CJ, Zhu J, Sandler AB, et al.: Outcome of patients with a performance status of 2 in Eastern Cooperative Oncology Group Study E1594: a Phase II trial in patients with metastatic nonsmall cell lung carcinoma . Cancer 92 (10): 2639-47, 2001.  [PUBMED Abstract]

  25. Tester WJ, Stephenson P, Langer CJ, et al.: ECOG 1599: randomized phase II study of paclitaxel/carboplatin or gemcitabine/cisplatin in performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC). [Abstract] J Clin Oncol 22 (Suppl 14): A-7055, 630s, 2004. 

  26. Vansteenkiste JF, Vandebroek JE, Nackaerts KL, et al.: Clinical-benefit response in advanced non-small-cell lung cancer: A multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol 12 (9): 1221-30, 2001.  [PUBMED Abstract]

  27. Hickish TF, Smith IE, O'Brien ME, et al.: Clinical benefit from palliative chemotherapy in non-small-cell lung cancer extends to the elderly and those with poor prognostic factors. Br J Cancer 78 (1): 28-33, 1998.  [PUBMED Abstract]

  28. Miller JI Jr, Phillips TW: Neodymium:YAG laser and brachytherapy in the management of inoperable bronchogenic carcinoma. Ann Thorac Surg 50 (2): 190-5; discussion 195-6, 1990.  [PUBMED Abstract]

  29. Ung YC, Yu E, Falkson C, et al.: The role of high-dose-rate brachytherapy in the palliation of symptoms in patients with non-small-cell lung cancer: a systematic review. Brachytherapy 5 (3): 189-202, 2006 Jul-Sep.  [PUBMED Abstract]

  30. Danson S, Middleton MR, O'Byrne KJ, et al.: Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer 98 (3): 542-53, 2003.  [PUBMED Abstract]

  31. Pfister DG, Johnson DH, Azzoli CG, et al.: American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol 22 (2): 330-53, 2004.  [PUBMED Abstract]

  32. Smit EF, van Meerbeeck JP, Lianes P, et al.: Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975. J Clin Oncol 21 (21): 3909-17, 2003.  [PUBMED Abstract]

  33. Kubota K, Watanabe K, Kunitoh H, et al.: Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group. J Clin Oncol 22 (2): 254-61, 2004.  [PUBMED Abstract]

  34. Georgoulias V, Ardavanis A, Agelidou A, et al.: Docetaxel versus docetaxel plus cisplatin as front-line treatment of patients with advanced non-small-cell lung cancer: a randomized, multicenter phase III trial. J Clin Oncol 22 (13): 2602-9, 2004.  [PUBMED Abstract]

  35. Sandler AB, Nemunaitis J, Denham C, et al.: Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 18 (1): 122-30, 2000.  [PUBMED Abstract]

  36. Bezjak A, Dixon P, Brundage M, et al.: Randomized phase III trial of single versus fractionated thoracic radiation in the palliation of patients with lung cancer (NCIC CTG SC.15). Int J Radiat Oncol Biol Phys 54 (3): 719-28, 2002.  [PUBMED Abstract]

  37. Sundstrøm S, Bremnes R, Aasebø U, et al.: Hypofractionated palliative radiotherapy (17 Gy per two fractions) in advanced non-small-cell lung carcinoma is comparable to standard fractionation for symptom control and survival: a national phase III trial. J Clin Oncol 22 (5): 801-10, 2004.  [PUBMED Abstract]

  38. Lester JF, Macbeth FR, Toy E, et al.: Palliative radiotherapy regimens for non-small cell lung cancer. Cochrane Database Syst Rev (4): CD002143, 2006.  [PUBMED Abstract]

  39. Macbeth F, Toy E, Coles B, et al.: Palliative radiotherapy regimens for non-small cell lung cancer. Cochrane Database Syst Rev (3): CD002143, 2001.  [PUBMED Abstract]


Glossary Terms

Level of evidence 1iiA
Randomized, controlled, nonblinded clinical trial with total mortality as an endpoint. See Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (PDQ®) for more information.
Level of evidence 1iiC
Randomized, controlled, nonblinded clinical trial with carefully assessed quality of life as an endpoint. See Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (PDQ®) for more information.


Table of Links

1http://www.cancer.gov/cancertopics/pdq/levels-evidence-adult-treatment/HealthPr
ofessional
2http://www.cancer.gov/search/viewclinicaltrials.aspx?version= heal
thprofessional &cdrid=65871
3http://www.cancer.gov/search/viewclinicaltrials.aspx?version= heal
thprofessional &cdrid=68012
4http://www.cancer.gov/cancertopics/pdq/supportivecare/cardiopulmonary/HealthPro
fessional
5http://www.cancer.gov/search/viewclinicaltrials.aspx?version= heal
thprofessional &cdrid=651994
6http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?Diagnosis=38942&tt=1&a
mp;format=2&cn=1
7http://www.cancer.gov/clinicaltrials