Related Pages Drug Information Summaries 1 NCI's drug information summaries provide consumer-friendly information about certain drugs that are approved by the U.S. Food and Drug Administration (FDA) to treat cancer or conditions related to cancer. Breast Cancer Home Page 2 NCI's gateway for information about breast cancer. Prostate Cancer Home Page 3 NCI's gateway for information about prostate cancer. Stomach (Gastric) Cancer Home Page 4 NCI's gateway for information about stomach (gastric) cancer. Head and Neck Cancer Home Page 5 NCI's gateway for information about head and neck cancer.

Brand name(s): Taxotere®

• Approved for head and neck cancer
• Approved for gastric cancer
• Approved for breast cancer
• Approved for prostate cancer

Full prescribing information ⁶ is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

On October 17, 2006, the FDA approved docetaxel (Taxotere® Injection Concentrate, made by Sanofi-Aventis) for use in combination with cisplatin and fluorouracil for the induction treatment of patients with inoperable, locally advanced squamous cell carcinoma of the head and neck (SCCHN).

The safety and efficacy of docetaxel as induction chemotherapy for patients with SCCHN were evaluated in a multicenter, open-label, randomized trial. In this study, 358 patients with previously untreated inoperable, locally advanced SCCHN, and WHO performance status 0 or 1, received either docetaxel 75 mg/m2 followed by cisplatin 75 mg/m2 on Day 1, followed by 5-fluorouracil 750 mg/m2/day as a continuous infusion on Days 1-5 (TPF), or cisplatin 100 mg/m2 on Day 1, followed by 5-fluorouracil 1000 mg/m2/day as a continuous infusion on Days 1-5 (PF).

These regimens were administered every three weeks for four cycles. Four to seven weeks after chemotherapy, patients whose disease had not progressed received radiotherapy. Radiation was delivered either with a conventional or an accelerated/hyperfractionated regimen. Surgical resection was allowed following chemotherapy, before or after radiotherapy.

The trial’s primary endpoint was progression-free-survival (PFS) and was defined as time from randomization to disease progression or death from any cause, whichever occurred first. Median PFS was significantly longer in the TPF arm (11.4 months) than in the PF arm (8.3 months), (p= 0.0077) [hazard ratio 0.71 (0.56, 0.91)].

Median overall survival was significantly longer in the TPF arm (18.6 months) than in the PF arm (14.2 months), [hazard ratio 0.71 (0.56, 0.90)].

The most frequent adverse events on the TPF arm were

• neutropenia (93 percent)
• anemia (89 percent)
• alopecia (81 percent)
• stomatitis/esophagitis (55 percent)
• nausea (47 percent)

Grade 3 or 4 adverse events with a greater than 5 percent frequency in patients on the TPF arm were

• neutropenia (76 percent)
• alopecia (11 percent)
• infection (9 percent)
• anemia (9 percent)
• weight loss (7 percent)
• thrombocytopenia (5 percent)

Approximately 5 percent of the TPF arm patients had febrile neutropenia and 14 percent had neutropenic infection. Compared to patients receiving PF, patients receiving TPF had more alopecia, neutropenia, diarrhea, neurosensory abnormality, neutropenic infection, fluid retention, and altered taste or sense of smell.

For this SCCHN indication, the recommended docetaxel dose is 75 mg/m2 administered as a one-hour intravenous infusion, followed by cisplatin 75 mg/m2 intravenously over one hour on Day 1, followed by fluorouracil 750 mg/m2/day given as a 24-hour intravenous continuous infusion Days 1-5. Treatment is repeated every three weeks for four cycles.

On September 28, 2007, the FDA approved docetaxel for use in combination with cisplatin and fluorouracil (5-FU) for the induction treatment of patients with locally advanced SCCHN.

The safety and efficacy of docetaxel for the above indication were evaluated in a multicenter, open-label, randomized trial. In this study, 501 patients with previously untreated locally advanced SCCHN, and performance status 0 or 1, received either docetaxel 75 mg/m2 followed by cisplatin 100 mg/m2 on day 1, followed by 5-FU 1000 mg/m2/day as a continuous infusion on Days 1-4 (TPF) or cisplatin 100 mg/m2 on Day 1, followed by 5-FU 1000 mg/m2/day as a continuous infusion on Days 1-5 (PF).

These regimens were administered every three weeks for three cycles. All patients in both treatment arms who did not have progressive disease following induction chemotherapy received seven weeks of chemoradiotherapy (CRT). During radiotherapy, carboplatin (AUC 1.5) was administered weekly as a one-hour infusion for a maximum of seven doses. Surgery could be considered at anytime following completion of CRT.

Overall survival was significantly prolonged with the docetaxel-containing regimen compared to the PF regimen (log­rank test, p=0.0058). The median survival was 70.6 months in the TPF group compared to 30.1 months in the PF group (hazard ratio = 0.70, 95 percent confidence interval: 0.54, 0.90).

The most frequent adverse events (>40 percent, any grade) on the TPF arm were neutropenia, anemia, nausea, alopecia, stomatitis, lethargy, vomiting, diarrhea, and anorexia. Neutropenic fever with or without infection occurred in greater than 5 percent of patients on the TPF arm. Grade 3 or 4 adverse events with a greater than 5 percent frequency in patients on the TPF arm were neutropenia, infection, stomatitis, nausea, esophagitis/dysphagia/odynophagia, anorexia, vomiting, and anemia. Neutropenia, alopecia, diarrhea, and anorexia were more frequently seen in the TPF arm.

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Gastric Cancer

This indication is based on the results of a multicenter, open-label, comparative clinical trial of 457 patients with locally advanced or metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for advanced disease. Patients were randomized to one of two arms.

• TCF (docetaxel 75 mg/m² in combination with cisplatin 75 mg/m² on Day 1 and fluorouracil 750 mg/m²/day by continuous infusion for five days every three weeks), or
• CF (cisplatin 100 mg/m² on Day 1 and fluorouracil 1000 mg/m²/day by continuous infusion for five days every four weeks). Four hundred and forty five patients were treated (TCF = 221, CF = 224)

Time-to-progression (TTP) was the trial’s primary endpoint and was defined as time from randomization to disease progression or death from any cause within 12 weeks of the last evaluable tumor assessment or within 12 weeks of the first infusion of study drugs for patients with no evaluable tumor assessment after randomization.

The hazard ratio (HR) for TTP was 1.47 (CF/TCF, 95 percent CI: 1.19-1.83) with a significantly longer TTP (p=0.0004) in the TCF arm. The median TTP in the TCF arm was 5.6 months compared to 3.7 months in the CF arm.

Overall survival was significantly longer (p=0.02) in the TCF arm with a HR of 1.29 (95 percent CI: 1.04-1.61). The median survival was 9.2 months in the TCF arm and 8.6 months in the CF arm.

Compared to patients receiving CF, patients receiving TCF had more neutropenia, fever, infection, febrile neutropenia, neutropenic infection, allergic reactions, fluid retention or peripheral edema, neurosensory toxicity, dizziness, alopecia, rash, nail changes, diarrhea, esophagitis/dysphagia/odynophagia, gastrointestinal pain or cramping, and tearing than patients receiving CF.

Eighty-two percent of patients on the TCF arm had grade 3 or 4 neutropenia and 32 percent had febrile neutropenia or neutropenic infection. The most frequent causes for treatment discontinuation were GI toxicities, flu-like symptoms and neurosensory toxicity. Patients receiving CF had more thrombocytopenia, vomiting, anorexia, constipation, and altered hearing.

For gastric carcinoma, the recommended dose of docetaxel is 75 mg/m2 administered as a one-hour infusion, followed by cisplatin 75 mg/m2, as a one-to-three hour infusion (both on Day 1 only), followed by fluorouracil 750 mg/m2 per day given as a 24-hour continuous infusion for five days, starting at the end of cisplatin infusion. Treatment is repeated every three weeks.

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Breast Cancer

Investigators enrolled 1491 women with node positive operable breast cancer in an international, multicenter, randomized trial (TAX316). Patients were stratified according to the number of positive axillary lymph nodes (1-3, 4+) and were randomly allocated to receive adjuvant treatment with either docetaxel 75 mg/m2 administered one-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC arm), or doxorubicin 50 mg/m2 followed by fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2 (FAC arm). Both regimens were given every three weeks for six cycles. After the last cycle of chemotherapy, patients with positive estrogen and/or progesterone receptors received tamoxifen 20 mg daily for up to five years.

The primary endpoint, disease free survival (DFS), included local and distant recurrences, contralateral breast cancer and deaths from any cause. At a median follow up of 55 months, results from a second interim analysis showed that the TAC regimen has significantly longer DFS than FAC, with an overall reduction in risk of relapse of 25.7 percent (hazard ratio= 0.74; 2-sided 95% CI= 0.60, 0.92, stratified log rank p = 0.0047). At the time of this interim analysis, based on 219 deaths, overall survival was longer for TAC than FAC (hazard ratio=0.69, 2-sided 95% CI=0.53, 0.90). There will be further analysis at the time survival data mature.

Women receiving TAC had an increase in anemia, grade > 3 neutropenia, stomatitis, amenorrhea, fever in absence of infection, hypersensitivity reactions, peripheral edema, neurosensory and skin events compared to those receiving FAC. The toxicity, while significant, did not cause a large number of patients to withdraw from treatment. As with other anthracycline/cyclophosphamide-containing regimens, long-term serious toxicity for the TAC regimen included leukemia (0.4 percent) and congestive heart failure (1.6 percent).

The approved dose of docetaxel for the adjuvant treatment of operable node-positive breast cancer is 75 mg/m2 administered one-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every three weeks for six cycles.

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Prostate Cancer

Safety and efficacy were demonstrated in TAX327, a randomized, multicenter global clinical trial designed to evaluate chemotherapy with docetaxel and prednisone in the treatment of men with metastatic, hormone-refractory prostate cancer. One thousand and six patients were randomized to one of three treatment arms:

• mitoxantrone + prednisone (MTX + P),
• weekly docetaxel (TXT qw) + prednisone, or
• docetaxel once every three weeks (TXT q3w) + prednisone

The primary efficacy endpoint was survival. The treatment arm of TXT q3w + prednisone demonstrated a statistically significant survival advantage over MTX+P control (median survival 18.9 vs. 16.5 months, respectively, p = 0.0094). The TXT qw + prednisone arm did not demonstrate an advantage in overall survival over the control arm.

Adverse events included anemia, neutropenia, infection, nausea, vomiting, anorexia, and fatigue. Adverse events occurring more frequently with TXT q3w compared to MTX+P included allergic reactions, fluid retention, sensory neuropathy, alopecia, nail changes, diarrhea, and stomatitis.

The approved dose for this indication is 75 mg/m2 docetaxel given intravenously as a one-hour infusion every 21 days on Day 1 plus 5 mg oral prednisone twice daily for 10 cycles.

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Glossary Terms

A drug used to treat symptoms of cancer of the colon, breast, stomach, and pancreas. It is also used in a cream to treat certain skin conditions. 5-FU stops cells from making DNA and it may kill cancer cells. It is a type of antimetabolite. Also called 5-fluorouracil and fluorouracil.

Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biological therapy.

The lack or loss of hair from areas of the body where hair is usually found. Alopecia can be a side effect of some cancer treatments.

Describes the ability of tumor cells to grow in the absence of androgens (hormones that promote the development and maintenance of male sex characteristics). Many early prostate cancers require androgens for growth, but advanced prostate cancers are often androgen-independent.

A condition in which the number of red blood cells is below normal.

An abnormal loss of the appetite for food. Anorexia can be caused by cancer, AIDS, a mental disorder (i.e., anorexia nervosa), or other diseases.

A drug that is used to treat advanced ovarian cancer that has never been treated or symptoms of ovarian cancer that has come back after treatment with other anticancer drugs. It is also used together with other drugs to treat advanced, metastatic, or recurrent non-small cell lung cancer and is being studied in the treatment of other types of cancer. Carboplatin is a form of the anticancer drug cisplatin and causes fewer side effects in patients. It attaches to DNA in cells and may kill cancer cells. It is a type of platinum compound. Also called Paraplatin.

Treatment that combines chemotherapy with radiation therapy. Also called chemoradiation.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

Having to do with the opposite side of the body.

Difficulty swallowing.

Swelling caused by excess fluid in body tissues.

Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.

In clinical trials, an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives. Some examples of endpoints are survival, improvements in quality of life, relief of symptoms, and disappearance of the tumor.

Inflammation of the esophagus (the tube that carries food from the mouth to the stomach).

A condition marked by fever and a lower-than-normal number of neutrophils in the blood. A neutrophil is a type of white blood cell that helps fight infection. Having too few neutrophils increases the risk of infection.

The place where the esophagus is connected to the stomach.

Radiation treatment in which the total dose of radiation is divided into small doses and treatments are given more than once a day. Also called hyperfractionated radiation therapy and superfractionated radiation therapy.

An exaggerated response by the immune system to a drug or other substance.

Initial treatment used to reduce a cancer. Induction therapy is followed by other treatments, such as chemotherapy, radiation therapy, and hormone therapy to get rid of cancer that remains. Also called first-line therapy, primary therapy, and primary treatment.

A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion.

Into or within a vein. Intravenous usually refers to a way of giving a drug or other substance through a needle or tube inserted into a vein. Also called IV.

A statistics term. The middle value in a set of measurements.

The time from either diagnosis or treatment at which half of the patients with a given disease are found to be, or expected to be, still alive. In a clinical trial, median survival time is one way to measure how effective a treatment is. Also called median overall survival and median survival.

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).

Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.

A nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. It usually begins in the hands or feet and gets worse over time. Neuropathy may be caused by physical injury, infection, toxic substances, disease (such as cancer, diabetes, kidney failure, or malnutrition), or drugs, including anticancer drugs. Also called peripheral neuropathy.

A condition in which there is a lower-than-normal number of neutrophils (a type of white blood cell).

Cancer that has spread to the lymph nodes.

A measure of how well a patient is able to perform ordinary tasks and carry out daily activities.

A lymph node in the area of the armpit (axilla) to which cancer has spread. This spread is determined by surgically removing some of the lymph nodes and examining them under a microscope to see whether cancer cells are present.

The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins.

Cancer that is growing, spreading, or getting worse.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

Inflammation or irritation of the mucous membranes in the mouth.

A condition in which there is a lower-than-normal number of platelets in the blood. It may result in easy bruising and excessive bleeding from wounds or bleeding in mucous membranes and other tissues.