sanofi-aventis announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has granted a positive opinion for the use of Taxotere (docetaxel) in combination with cisplatin and 5 -fluorouracil for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).
The CHMP based its decision on the significant improvement of survival demonstrated by the results of the phase III trial, TAX 324, (71 months with the Taxotere -based regimen versus 30 months with the control regimen). The US Food and Drug Administration (FDA) approved Taxotere for this additional indication on September 28, 2007.
"For many years, we have waited for a new therapeutic option for this very difficult pathology. The survival improvement seen with this Taxotere-based regimen is extraordinary for locally advanced squamous cell carcinoma, and will provide a new, multidisciplinary approach to the management of our patients," said Marshall Posner, MD, medical director, Head and Neck Oncology Programme, Dana-Farber Cancer Institute in Boston.
Taxotere is currently approved in 5 different cancer types in Europe and the US and this new indication for Taxotere is the 11th in Europe (the 8th in the US).
Patients were treated with for three cycles of chemotherapy every three weeks 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.
Patients entering TAX 324 had tumours 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 larynx function. Participants in the trial had either stage III or IV SCCHN with no distant metastases.
Among patients treated with Taxotere-based therapy (TPF, n=255) overall survival was significantly improved compared to patients receiving just cisplatin and 5-fluorouracil (PF, n=246); the relative risk of death was 30 per cent lower (HR 0.70; p=0.0058). Patients treated with TPF had a longer median overall survival of 71 months vs. 30 months for patients receiving PF, representing a Page 2 sur 3 more than three year improvement in median OS for patients treated with TPF. Survival at three years was 62 per cent in the TPF arm compared to 48 per cent in the PF arm.
Overall, the incidence of grade 3/4 toxicity was 65 per cent in the Taxotere arm (TPF) compared to 62 per cent in the group receiving cisplatin and fluorouracil (PF). Patients treated with TPF had more febrile neutropenia (12 per cent vs 7 per cent), neutropenic infection (12 per cent vs 8 per cent), and grade 3/4 neutropenia (84 per cent vs. 56 per cent), alopecia (4 per cent vs 1 per cent) and diarrhoea (7 per cent vs. 3 per cent) than those in the PF group. Patients in the PF group had more grade 3/4 thrombocytopenia (11 per cent vs. 4 per cent), stomatitis (27 per cent vs. 21 per cent), lethargy (10 per cent vs. 5 per cent) and vomiting (10 per cent vs. 8 per cent). The incidence of other grade 3/4 events was similar between the two groups, such as nausea, anorexia and constipation. The incidence of treatment delays was significantly lower in the TPF group indicating a diminution of the toxicity in this treatment arm. Patients treated in the TPF arm received a prophylactic antibiotherapy in order to better control the haematological toxicity, mainly febrile neutropenia.
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.
Taxotere is currently approved in 5 different cancer types in Europe and the US: In the United States and in Europe Taxotere is approved to treat patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. It is also approved in Europe in combination with doxorubicin for patients who have received prior cytotoxic therapy for this condition and in combination with capecitabine after failure of cytotoxic therapy which would have included anthracycline. In the adjuvant setting (post surgery) it is approved in the US and in Europe in combination with doxorubicin and cyclophosphamide (TAC regimen) for the treatment of patients with operable, node-positive breast cancer. Finally, in Europe, Taxotere is approved in combination with trastuzumab for the treatment of patients with metastatic breast cancer- overexpressing HER2 receptor.
In the US and in Europe, Taxotere, in combination with cisplatin, is approved for the treatment of patients with unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not received prior chemotherapy, and it also is approved, as a single agent, for patients with unresectable locally advanced or metastatic NSCLC after failure of prior platinum based chemotherapy.
Taxotere is approved for use in combination with prednisone as a treatment for androgen independent (hormone-refractory) metastatic prostate cancer in the US and in Europe.
The FDA and the Committee for Medicinal Products for Human Use (CHMP) of the European Agency for the Evaluation of Medicinal Products (EMEA) approved in March 2006, the use of Taxotere Injection Concentrate in combination with cisplatin and 5-fluorouracil for the treatment of patients with advanced stomach (gastric) cancer, including cancer of the gastro oesophageal (GE) junction, who have not received prior chemotherapy for advanced disease.
In October 2006, the European Medicines Agency (EMEA) and the FDA approved Taxotere (docetaxel) Injection Concentrate 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). In September 2007, the FDA approved Taxotere in combination with cisplatin and 5-fluorouracil for the induction therapy of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) prior to chemoradiotherapy and surgery.