Weekly high-dose paclitaxel in metastatic and locally advanced breast cancer: a preliminary report

The optimal dose and schedule for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced breast cancer are not known. Based on our phase I study in non-small cell lung cancer, in which the dose intensity of paclitaxel was successfully escalated by using a weekly schedule, we initiated a phase II study of weekly paclitaxel in previously untreated patients with metastatic breast cancer (MBC) and locally advanced breast cancer (LABC). Treatment consists of weekly paclitaxel 175 mg/m2 intravenously over 3 hours for 6 weeks, followed by a 2-week break. Doses are modified for neutropenia (absolute neutrophil count < 1,500/microL), bilirubin levels greater than 1.5 times normal, or greater than grade 1 neuropathy. Patients with MBC continue treatment until disease progression. Patients with LABC receive one to two cycles before proceeding to surgery if resectable. Thus far, 15 patients, eight with MBC and seven with LABC, are assessable for response and/or toxicity. Most patients have required dose modification, with median delivery of 75% (cycle 1) and 50% (cycle 2) of the planned dose of paclitaxel. Neutropenia has been the most common cause of dose reductions, although only one patient required treatment for neutropenic fever. Six patients have developed grade 2/3 peripheral sensory neuropathy, but with dose reductions many have continued treatment with stable or improving neurologic symptoms. Objective responses have been seen in 12 of 14 assessable patients, including six with MBC (one complete response, five partial responses) and six with LABC (two complete responses, four partial responses), for an overall response rate of 86% (95% confidence interval, 66% to 96%). All responding LABC patients have been rendered free from disease at surgery. These preliminary results are very encouraging. Accrual to the study continues.