FDA Approves Docetaxel (Taxotere) for Induction Chemotherapy in Head & Neck Cancer

On September 28, 2007, the U. S. Food and Drug Administration (FDA) approved docetaxel (Taxotere® Injection Concentrate, Sanofi-Aventis) for use in combination with cisplatin and fluorouracil (5-FU) for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).

The safety and efficacy of Taxotere® for the above indication were evaluated in a multi-center, open-label, randomized trial.  In this study, 501 patients with previously untreated locally advanced SCCHN, and performance status 0 or 1, received either Taxotere® 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 regimen) 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 regimen).  These regimens were administered every 3 weeks for 3 cycles.  All patients in both treatment arms who did not have progressive disease following induction chemotherapy received 7 weeks of chemoradiotherapy (CRT).  During radiotherapy, carboplatin (AUC 1.5) was administered weekly as a 1-hour infusion for a maximum of 7 doses.  Surgery could be considered at anytime following completion of CRT.

Overall survival was significantly prolonged with the Taxotere®-containing regimen (TPF) compared to the PF regimen (log‑rank 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% confidence interval:  0.54, 0.90).

The most frequent adverse events (>40%, 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% of patients on the TPF arm. Grade 3 or 4 adverse events with a greater than 5% 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.

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at www.fda.gov/cder/foi/label/2007/020449s045lbl.pdf.

Tags: 5-flurouracil, 5-FU, cisplatin, docetaxel, Head & Neck Cancer, Induction Chemotherapy, Platinol, Radiation Therapy, Squamous Cell Carcinoma, Taxotere