Randomized phase II study of high-dose paclitaxel with or without amifostine in patients with metastatic breast cancer

Purpose: To determine whether the neurotoxicity of paclitaxel 250 mg/m(2) given over 3 hours every 3 weeks could be reduced by pretreatment with amifostine 910 mg/m(2). Secondary objectives included comparing myelosuppression, myalgias, and response rates of the two groups. Patients and Methods: Forty women with metastatic breast cancer were randomized to receive either paclitaxel atone (arm 1) or paclitaxel preceded by amifostine (arm 2), All were assessable for toxicity, and 37 were assessable far response, At baseline and after each cycle, all patients completed questionnaires for neurologic symptoms and had standardized neurologic examinations, including objective assessments of power and vibration sense. In addition, standard follow-up assessments for other toxicities and tumor response were undertaken, Changes from baseline after courses 1, 2, and 3 were assessed. The sample size was sufficient to detect a 50% improvement in the expected determination in sensory change, Results: There were no differences observed in any of the measures of neurotoxicity, Other toxicity wets similar in arms 1 and 2, including hair loss (95% v 90%), neurosensory changes (100% v 100%), fatigue/lethargy (85% v 90%), myalgia (95% v 90%), and grade 4 neutropenia (47% v 60%). Nausea, vomiting, dizziness, hypotension, and sneezing were mare common in the amifostine arm. Response rates (22.2% v 36.8%) and paclitaxel pharmacokinetics were not significantly different. Conclusion: There was no protection from paclitaxel-related neurotoxicity or hematologic toxicity in this study These results suggest that the mechanism of action of paclitaxil-related toxic effects is not amenable to the cytoprotective action of amifostine. (C) 1999 by American Society of Clinical Oncology.