FDA Approves Taxotere for Inoperable Head & Neck Cancer

November 1, 2006

The FDA has approved Taxotere (docetaxelfor injection, Sanofi-Aventis), in combinationwith cisplatin and fluorouracil andadministered prior to radiotherapy, forthe treatment of patients with inoperable,locally advanced squamous cell carcinomaof the head and neck (SCCHN).

ROCKVILLE, Maryland--TheFDA has approved Taxotere (docetaxelfor injection, Sanofi-Aventis), in combinationwith cisplatin and fluorouracil andadministered prior to radiotherapy, forthe treatment of patients with inoperable,locally advanced squamous cell carcinomaof the head and neck (SCCHN).

The agency granted marketing approvalto the drug on the basis of phaseIII trial results showing patients treatedwith Taxotere and the two chemotherapeuticagents had a longer progressionfreesurvival and overall survival thanthose who received only the two cytotoxicdrugs. The difference in both endpointswas statistically significant.

SCCHN, a group of related cancers,accounts for approximately 3% of all newcancers diagnosed in the United States,according to the FDA. These malignanciesmostly develop in the cells lining themucosal surfaces in the head and neck,including those of the mouth, nose, andthroat.

"Survival rates for advanced head andneck cancer have historically been low,"noted Marshall Posner, MD, medicaldirector of the Head and Neck OncologyProgram at the Dana-Farber CancerInstitute. "This study has shown thatinduction therapy with a Taxotere,cisplatin, and 5-fluorouracil [TPF] regimenincreases survival. With this approval,I hope to see TPF become thestandard of care for induction therapyfor patients with this type of cancer."

The new indication for SCCHN isTaxotere's seventh in the United Statessince the drug received its initial approvalin 1996 as a treatment for breast cancer.Taxotere is a member of the taxoid family,and produces its antineoplastic effectby disrupting the network of microtubulesthat cells require for mitotic andinterphase cellular functions.

TAX323
Sanofi-Aventis submitted data from amulticenter, open-label, randomizedphase III trial, designated EORTC 24971/TAX323, which was conducted under theauspices of the European Organizationfor Research and Treatment of Cancer(EORTC).

Investigators enrolled 358 patientswith previously untreated inoperable, locallyadvanced SCCHN who had a WHOperformance status of 0 or 1. They randomized177 participants to receive Taxotere 75 mg/m2 followed by cisplatin75 mg/m2 on day 1, followed by fluorouracil750 mg/m2/d as a continuous infusionon days 1 to 5 (TPF arm). Theyassigned another 181 patients to receivecisplatin 100 mg/m2 on day 1, followedby fluorouracil 1,000 mg/m2/d as a continuousinfusion on days 1 to 5 (PF arm).

Researchers administered the regimensevery 3 weeks for four cycles. Whenpatients completed their chemotherapy,those without disease progression receivedlocoregional radiation treatmentsby either a conventional fraction regimenor an accelerated/hyperfractionatedregimen. The study protocol allowed surgicalresections following chemotherapy,either before or after a patient underwentradiation therapy.

With a median follow up of 33.7months, patients in the TPF arm had amedian progression-free survival of 11.4months, a significant advantage over themedian 8.3 months in the PF group(P = .0077). The Taxotere-treated patientsalso had a significantly longer medianoverall survival of 18.6 months at51.2 months median follow up vs 14.2months for the PF arm (P = .0055), witha 29% reduction in risk of death.

The TPF group also had the betteroverall response rate to chemotherapy,67.8% vs 53.6% in the PF-treated patients(P = .006), and better overall responseto study treatment, chemotherapywith or without radiotherapy, 72.3% vs58.6% in the PF arm (P = .006).