On October 17, 2006, the U. S. Food and Drug Administration (FDA) approved docetaxel (Taxotere Injection Concentrate, 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 Taxotere 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 Taxotere 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 4 cycles. Four to 7 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%), anemia (89%), alopecia (81%), stomatitis/esophagitis (55%), and nausea (47%). Grade 3 or 4 adverse events with a greater than 5% frequency in patients on the TPF arm were neutropenia (76%), alopecia (11%), infection (9%), anemia (9%), weight loss (7%), and thrombocytopenia (5%). Approximately 5% of the TPF arm patients had febrile neutropenia and 14% 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 Taxotere dose is 75 mg/m2 administered as a 1-hour intravenous infusion, followed by cisplatin 75 mg/m2 intravenously over 1 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 3 weeks for 4 cycles.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at www.fda.gov/cder/foi/label/2006/020449s039lbl.pdf. 
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by phone at 1-800-FDA-1088, by facsimile 1-800-FDA-0178, by mail, or by using the Form 3500 at http://www.fda.gov/medwatch/index.html.
For further information related to oncology
drug approvals, regulatory information, and
other oncology resources, please refer to the
FDA “Oncology Tools” website at
www.fda.gov/cder/cancer.
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