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) g iven over 3 hours every 3 weeks could be reduced by pretreatment with amifo stine 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 random ized to receive either paclitaxel atone (arm 1) or paclitaxel preceded by a mifostine (arm 2), All were assessable for toxicity, and 37 were assessable far response, At baseline and after each cycle, all patients completed que stionnaires for neurologic symptoms and had standardized neurologic examina tions, including objective assessments of power and vibration sense. In add ition, standard follow-up assessments for other toxicities and tumor respon se were undertaken, Changes from baseline after courses 1, 2, and 3 were as sessed. The sample size was sufficient to detect a 50% improvement in the e xpected determination in sensory change, Results: There were no differences observed in any of the measures of neuro toxicity, 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, vomit ing, dizziness, hypotension, and sneezing were mare common in the amifostin e arm. Response rates (22.2% v 36.8%) and paclitaxel pharmacokinetics were not significantly different. Conclusion: There was no protection from paclitaxel-related neurotoxicity o r hematologic toxicity in this study These results suggest that the mechani sm of action of paclitaxil-related toxic effects is not amenable to the cyt oprotective action of amifostine. (C) 1999 by American Society of Clinical Oncology.