The US Food and Drug Administration (FDA) has approved Taxotere Injection Concentrate combined with cisplatin and 5-fluorouracil for induction therapy of locally advance squamous cell carcinoma of the head and neck before chemoradiotherapy and surgery.
The Agency says the approval was based on the results of Phase II randomized, open label, international human trial, TAX 324, which demonstrated that Taxotere is safe and efficacious and appreciably improves survival.
Of 251 patients who received Taxotere based therapy (TPF), overall survival was substantially improved, compared to the 243 patients who just received cisplatin and 5-fluorouracil (PF). The relative risk of death for the TPF patients was 30% lower. The median overall survival of the TPF patients was 70.6 months, versus 30.1 months for the PF only patients.
Clinical investigator, Marshall Posner, MD, Medical Director of the Head and Neck Oncology Program at Dana-Farber Cancer Institute in Boston, said “The TAX 324 trial found that the addition of Taxotere to standard induction chemotherapy significantly improved patient survival, adding years to patients’ lives. 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 the patients that entered TAX 324 had tumors of the oropharynx, larynx, hypopharynx or oral cavity that either could not be extracted, were deemed potentially operable but unlikely to be cured with surgery, or could not be removed in order to maintain organ function. The patients who took part in the trail had either stage III or IV squamous cell carcinoma of the head and neck (SCCHN) with no distant metastases.
They were treated every 3 weeks for 3 cycles with either TPG (Taxotere 75 mg/m2 + cisplatin 100 mg/m2 and 5-fluorouracil 1000 mg/m2 a day for 4 days) or PF (intravenous cisplatin 100 mg/m2 followed by 5- fluorouracil 1000 mg/m2 a day for 5 days), which was the standard therapy.
Both the TPG and PF groups were given chemotherapy (carboplatin) every week combined with radiation therapy for a total of seven weeks. This was then followed by surgery for those patients identified as candidates. The main aim of the study was to evaluate overall survival. Secondary endpoint included progression-free survival, response rates, toxicity, clinical benefits and quality of life.
In the TPF arm overall incidence of grade ¾ toxicity was 65%, versus 62% in the PF group.
Here are some other comparisons:
— febrile neutropenia in the TPF group 12%
— febrile neutropenia in the PF group 7%
— neutropenic infection in the TPF group 12%
— neutropenic infection in the PF group 8%
— grade 3/4 neutropenia in the TPF group 84%
— grade 3/4 neutropenia in the PF group 56%
— dizziness in the TPF group 4%
— dizziness in the PF group 2%
— alopecia in the TPF group 4%
— alopecia in the PF group 1%
— diarrhea in the TPF group 7%
— diarrhea in the PF group 3%
— grade 3/4 thrombocytopenia in the TPF group 4%
— grade 3/4 thrombocytopenia in the PF group 11%
— stomatitis in the TPF group 21%
— stomatitis in the PF group 27%
— lethargy in the TPF group 5%
— lethargy in the PF group 10%
— stomatitis in the TPF group 8%
— stomatitis in the PF group 10%
The incidence of other grade 3/4 events was similar between the two groups, such as nausea, anorexia and constipation.
Annually, over 640,000 people are diagnosed globally with head and neck cancers. Head and neck cancers kill over 350,000 people each year worldwide. Head and neck cancer is a group of many related diseases that generally start in the cells that line the mucosal surfaces of the mouth, tongue, tonsils and voice box. Head and neck cancers include cancers of the oral cavity, pranasal sinuses and nasal cavity, salivary glands, pharynx, larynx, and lymph nodes in the upper part of the neck.
Nancy Leupold, survivor, President and Founder of Support for People with Oral and Head and Neck Cancer (SPOHNC), said “Head and neck cancer is particularly hard to treat and if not detected early has low survival rate. The availability of effective therapies that advance treatment and help patients live longer is very welcome news for the cancer community.”
— http://www.sanofi-aventis.com
— http://www.taxotere.com
Written by: Christian Nordqvist