EMEA and FDA extend drug-label based on results of the EORTC 24971 trial

In its September meeting 2006, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) gave a positive opinion to include the use of docetaxel in combination with the current standard treatment – cisplatin and 5 – fluorouracil – for the induction treatment of patients with inoperable locally advanced squamous cell carcinoma of the head and neck.

On October 18, the US Food and Drug Administration (FDA) gave its approval to the new treatment as well. According to Steven Galson, M.D., director of FDA’s Center for Drug Evaluation and Research, it will “provide prescribers with a new treatment option that has been shown to help slow the spread of the disease and prolong patients’ survival.”

This drug – label extension of Taxotere (docetaxel) was possible due to the EORTC 24971 phase III, open label randomized trial, involving 358 patients, evaluating the benefit derived from docetaxel – based combination in inoperable locally advanced head and neck cancer.

Patients treated with the regimen prior to surgery or radiation had significantly longer median overall survival compared to a standard treatment of cisplatin and 5-fluorouracil; with a 28 percent risk reduction of the, 18.6 vs 14.5 months (p=0.0128). Patients receiving the docetaxel-based regimen also had a significantly longer time-to-disease progression of 11.4 months, compared with 8.3 months (P=0.015) for the patients receiving standard therapy. These results have been associated to an improvement of the safety profile.

”Very few treatment options are currently available for patients with head and neck cancer”, said Jan B. Vermorken, MD, PhD, Head of Oncology Department, University Hospital Antwerp and Chair of the EORTC Head and Neck Cancer Group and Principal Investigator of the EORTC 24971 study. “EORTC 24971/TAX 323 is the first study to identify a neoadjuvant chemotherapy regimen that extended life for patients with inoperable head and neck cancer; so a European approval may offer physicians another treatment option to manage this disease.”

”This label extension once again exemplifies nicely how the pharmaceutical industry and academic clinical research bring about innovation in cancer research. I am confident that an increase in these partnerships will prove to be extremely fruitful for cancer research in Europe”, adds Françoise Meunier, MD, PhD, Director General of the EORTC.

About the EORTC 24971 Trial

Patients in the trial were randomly assigned to receive one of two treatments. Of the 358 participants, 177 received an infusion of docetaxel 75 mg/m2 plus cisplatin 75 mg/m2 on day one and a five-day continuous infusion of 5-fluorouraci (5-FU) 750 mg/m2 and 181 patients received an infusion of a standard treatment consisting of cisplatin 100 mg/m2 on day one followed by a five-day continuous infusion of 5-fluorouracil (5-FU) 1000 mg/m2/d. Treatment cycles were repeated every three weeks for a total of four cycles. Patients received radiation therapy following chemotherapy within four to seven weeks after completing the last cycle of chemotherapy. Radiation therapy was administered five days a week for seven weeks. Patients receiving the cisplatin and 5-fluorouracil (5 – FU) regimen showed greater grade 3-4 nausea (7/2% vs. 0.6%), vomiting (5.0% vs. 0.6 %) stomatitis (11% vs. 4.0 %) during chemotherapy and more toxic deaths (5.5 vs. 2.3 % of the total number of patients) when compared to the docetaxel-based regimen.

Patients treated with the docetaxel-containing regimen experienced significantly less deterioration of their Global Health Score compared to those treated with the standard regimen. The Performance Status Scale was also significantly in favor of the docetaxel-containing regimen. The head and neck subscales of the Performance Status Scale are designed to measure disturbances of speech and eating. Median time to first deterioration of WHO performance status was longer in the docetaxel-arm with a 30% risk reduction of WHO performance status deterioration (p=0.0158). The EORTC trial was supported by Sanofi-Aventis.

About Head and Neck Cancer

More than 640 000 people worldwide are diagnosed with head and neck cancer every 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, nose, and throat. 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.