Phase III comparison of high-dose paclitaxel plus cisplatin plus granulocyte colony-stimulating factor versus low-dose paclitaxel plus cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393

Purpose: To determine dose-response effects and the activity of paclitaxel combined with cisplatin in patients with incurable squamous cell carcinoma of the head and neck. Patients and Methods: Two hundred ten patients with locally advanced, recur rent, or metastatic disease were randomly placed in either Arm A, paclitaxe l 200 mg/m(2) (24-hour infusion) + cisplatin 75mg/m(2) + granulocyte colony -stimulating factor, or Arm B, paclitaxel 135 mg/m(2) (24-hour infusion) cisplatin 75 mg/m(2). Cycles were repeated every 3 weeks until progression or a total of 12 cycles for complete responses. Primary outcomes were event -free and overall survival. Results: No significant differences in outcomes were observed between the h igh- and low-dose paclitaxel regimens. The estimated median survival was 7. 3 months (95% confidence interval, 6.0 to 8.6). The 1-year survival rate wa s 29%, and event-free survival was 4.0 months. The objective response rate (complete response plus partial response) war 35% for the high-dose patient s and 36% for the low-dose patients. Myelosuppression was the most frequent toxicity: grade 3 or 4 granulocytopenia, 70% of patients in Arm A and 78% in Arm a; febrile neutropenia, 27% of patients in Arm A and 39% in Arm a. G rade 5 toxicities occurred in 22 patients (10.5%). Treatment was terminated early in 31% because of excessive toxicity or patient refusal. Conclusion: This phase III multicenter trial showed (1) no advantage for hi gh-dose paclitaxel and (2) excessive hematologic toxicity associated with b oth regimens. Therefore, neither of the paclitaxel regimens evaluated in th is trial can be recommended.