Neoadjuvant Taxotere® (docetaxel) + cisplatin/5-FU (TPF) - improves response and survival compared to standard cisplatin/5-FU (PF)

Neoadjuvant chemotherapy with docetaxel (T), cisplatin (P) and infusional 5-fluorouracil (F) improved response rates, progression free survival and overall survival compared to PF, and was better tolerated, according to a phase III trial of the EORTC Head and Neck Cancer Group, presented at the 40th Annual meeting of the American Society of Clinical Oncology. Results of phase II studies suggested that docetaxel may improve efficacy of standard cisplatin and infusional 5-fluorouracil (PF) in patients with locally advanced squamous cell carcinoma of the head and neck. This phase III trial compared 348 patients with nonresectable locally advanced squamous cell carcinoma of the head and neck, excluding that of nasopharynx, nasal & paranasal cavities.The standard arm (PF) included 181 patient treated with cisplatin at 100 mg/m2/day on day 1 and 5-fluorouracil at 1000 mg/m2 on days 1-5 every 21 days and 177 patients in the TPF group of docetaxel (75 mg/m2 on day 1, cisplatin at 75 mg/m2 and 5-fluorouracil at 750 mg/m2 on days 1-5 every 21 days. Planned treatment included 4 cycles unless there was progression, unacceptable toxicity or patient refusal. After 4-7 wks, all patients received conventional, accelerated, hyperfractionated radiotherapy unless there was progressive disease after cycle 1 or 2. Neck dissection was allowed before or three months after radiotherapy for residual disease. Median follow-up was 32 months. The TPF group showed significantly superior progression free survival (HR 0.72; 95% CI, 0.56 to 0.91, p=0.006), overall survival (HR 0.73, 95% CI, 0.57 to 0.94, p=0.016) and response rate (67.8% compared to 53.6%, p=0.007). The PF group had more grade 3-4 nausea (7.3% vs 0.6%), vomiting (5.0% vs 0.6%) and stomatitis (11.2% vs 4.6%) and more toxic deaths (5.5% vs 2.3%) than the TPF group.The authors concluded that TPF and radiotherapy improved response rate, progression free survival and overall survival compared to PF and radiotherapy, and was better tolerated.Reference...