Single-agent paclitaxel and paclitaxel plus ifosfamide in the treatment of head and neck cancer

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and ifosfamide both have activity when evaluated as single agents in patients with advanced squamous cell carcinoma of the head and neck. The Eastern Cooperative Oncology Group completed the first phase II trial of paclitaxel in this population, observing a 40% response rate. Confirmatory trials are in progress in the United States and Europe. The Eastern Cooperative Oncology Group is currently evaluating high-dose (200 mg/m²) and low-dose (135 mg/m²) paclitaxel in combination with cisplatin to assess dose-response effects, toxicity, and efficacy. In an effort to identify an alternate to the cisplatin/5-fluorouracil regimen, investigators at Johns Hopkins and the University of Michigan are evaluating the combination of paclitaxel/ifosfamide. The regimen is paclitaxel 170 mg/m² followed by ifosfamide 5 g/m² divided over 3 days with mesna. Granulocyte colony- stimulating factor is started 24 hours after completion of the ifosfamide infusion. To date, 13 patients with recurrent and metastatic squamous cell carcinoma of the head and neck have been enrolled in the study. Eight patients have had prior chemotherapy as part of initial curative treatment or for recurrent disease. The best response observed in 11 evaluable patients is five partial responses, five stable diseases, and one disease progression. On progression, patients who have not been treated with cisplatin/5-fluorouracil receive that combination as second-line therapy. The occurrence of severe, life-threatening toxicity, primarily myelosuppression, has caused this study to be terminated. However, the responses observed have prompted an evaluation of the reverse sequence (ifosfamide followed by paclitaxel), which is now accruing patients.