Expanded phase II trial of paclitaxel in metastatic breast cancer: A Southwest Oncology Group study

Background. The study was designed to evaluate the efficacy of paclitaxel i n metastatic breast cancer patients. The design was motivated by a report f rom FDA and NCI staff proposing assessment of pre- and post-treatment sympt oms as a means of evaluating treatment effectiveness [1]. Methods. Patients with symptomatic and/or measurable metastatic breast cancer with prior tre atment received paclitaxel 210 mg/m(2) as a 3 hour infusion every three wee ks until toxicity or progression. A unique endpoint was subjective symptoma tic response, defined as an improvement in the Symptom Distress Scale score by greater than or equal to 3 points at two successive evaluations before treatment failure. Patients were also evaluated for objective response and toxicity. Results. Of 135 patients registered, 123 were eligible and treate d. The subjective symptomatic response rate for 93 symptomatic patients who completed forms was 40%, 95% confidence interval 29-51%. The objective res ponse rate in 77 patients with measurable disease was 19%, 95% confidence i nterval 11-30%. In patients with both measurable and symptomatic disease, 3 7% had symptomatic and 13% had objective responses. Median times to treatme nt failure and death were 4 and 11 months, respectively. Toxicity was great er than anticipated: 12% discontinued treatment due to toxicity, 29% develo ped at least one Grade 3 neuromuscular toxicity, and two patients died of s epsis while neutropenic. Conclusion. Paclitaxel by 3 hour infusion at a dos e of 210 mg/m(2) produced excessive neurotoxicity in patients with previous ly treated metastatic breast cancer. Both sustained subjective symptom redu ction and objective responses were demonstrated, but dose reduction for rou tine practice is recommended.