Taxotere Granted FDA Approval to Treat Locally Advanced Head and Neck Cancer Prior to Chemoradiotherapy and Surgery
BRIDGEWATER, N.J., Oct. 1 -- Sanofi-aventis announced that the U.S. Food and Drug Administration (FDA) has approved Taxotere(R) (docetaxel) Injection Concentrate in combination with cisplatin and 5-fluorouracil for induction therapy of locally advanced squamous cell carcinoma of the head and neck (SCCHN) before patients undergo chemoradiotherapy and surgery.
The FDA based its approval on the results of the phase III randomized, open-label, international trial, TAX 324, which established the efficacy and safety of the Taxotere-based regimen in significantly improving survival.
Approval Based on Clinical Trial Tax 324
Among patients treated with Taxotere-based therapy (TPF, n=251) overall survival was significantly improved compared to patients receiving just cisplatin and 5-fluorouracil (PF, n=243); the relative risk of death was 30% lower (HR 0.70; p=0.0058). Patients treated with TPF had a longer median overall survival of 70.6 months vs. 30.1 months for patients receiving PF only, representing a more than three year improvement in median OS for patients treated with TPF. The probability to survive three years was 62% in the TPF arm compared to 48% in the PF arm.
"The TAX 324 trial found that the addition of Taxotere to standard induction chemotherapy significantly improved patient survival, adding years to patients' lives," noted clinical investigator Marshall Posner, MD, Medical Director of the Head and Neck Oncology Program at Dana-Farber Cancer Institute in Boston. "The approval of Taxotere to be given in combination with other standard chemotherapy as the first step in a therapeutic sequence followed by chemoradiotherapy and surgery is a significant advancement in treatment for patients with locally advanced head and neck cancer."
All patients entering TAX 324 had tumors of the oropharynx, larynx, hypopharynx or oral cavity that either could not be removed, were considered potentially operable but unlikely to be cured with surgery, or could not be removed in order to preserve organ function. Participants in the trial had either stage III or IV SCCHN with no distant metastases.
Patients were treated every three weeks for three cycles with either TPF (Taxotere 75 mg/m2 plus cisplatin 100 mg/m2 and 5-fluorouracil 1000 mg/m2 a day for four days) or PF (intravenous cisplatin 100 mg/m2 followed by 5- fluorouracil 1000 mg/m2 a day for five days), the standard therapy. Both groups of patients were then given weekly chemotherapy (carboplatin) together with radiation therapy for seven weeks, followed by surgery for those patients identified as candidates. The study was designed primarily to evaluate overall survival. Secondary endpoint included progression-free survival, response rates, toxicity, quality of life and clinical benefits.
Overall, the incidence of grade 3/4 toxicity was 65% in the Taxotere arm (TPF) compared to 62% in the group receiving cisplatin and fluorouracil (PF). Patients treated with TPF had more febrile neutropenia (12% vs 7%), neutropenic infection (12% vs 8%), and grade 3/4 neutropenia (84% vs. 56%), dizziness (4% vs. 2%), alopecia (4% vs 1%) and diarrhea (7% vs. 3%) than those in the PF group. Patients in the PF group had more grade 3/4 thrombocytopenia (11% vs. 4%), stomatitis (27% vs. 21%), lethargy (10% vs. 5%) and vomiting (10% vs. 8%). The incidence of other grade 3/4 events was similar between the two groups, such as nausea, anorexia and constipation.
Head and Neck Cancer, a Deadly Disease
More than 640,000 people worldwide are diagnosed with head and neck cancer each year, and more than 350,000 die from the disease annually. Head and neck cancer is a group of many related diseases that mostly begin in the cells that line the mucosal surfaces in the head and neck area such as the mouth, tongue, tonsils, throat and voicebox. The term encompasses cancers of the oral cavity, salivary glands, paranasal sinuses and nasal cavity, pharynx, larynx, and lymph nodes in the upper part of the neck.
"Head and neck cancer is particularly hard to treat and if not detected early has low survival rates," commented Nancy Leupold, survivor, President and Founder of Support for People with Oral and Head and Neck Cancer (SPOHNC). "The availability of effective therapies that advance treatment and help patients live longer is very welcome news for the cancer community."
About sanofi-aventis
Sanofi-aventis is one of the world leaders in the pharmaceutical industry, ranking number one in Europe. Backed by a world-class R&D organization, sanofi-aventis is developing leading positions in seven major therapeutic areas: cardiovascular, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine and vaccines. Sanofi-aventis is listed in Paris and in New York .
Forward Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future events, operations, products and services, and statements regarding future performance. Forward-looking statements are generally identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans" and similar expressions. Although sanofi-aventis' management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward- looking information and statements. These risks and uncertainties include those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in sanofi-aventis' annual report on Form 20-F for the year ended December 31, 2006. Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.