Weekly High-Dose Paclitaxel Produces High Response Rates in Advanced Breast Cancer

PROVIDENCE, RI--Weekly high-dose paclitaxel (Taxol) produces response rates similar to those seen with combination chemotherapy in patients with advanced breast cancer and merits further study, William M. Sikov, MD, said at an ASCO poster session.

Dr. Sikov and his colleagues in the Brown University Oncology Group reported an 86% response rate in patients with either metastatic or locally advanced breast cancer treated with paclitaxel at 175 mg/m² IV given over 3 hours for 6 weeks, followed by a 2-week break (see Table).

In this ongoing phase II trial, metastatic breast cancer patients continue treatment until disease progression or toxicity. Locally advanced patients rendered resectable proceed to surgery, adjuvant chemotherapy, and radiation.

To date, 29 untreated patients with metastatic breast cancer and 25 with locally advanced breast cancer have been treated with paclitaxel, with dose reductions for grade 2 or higher neutropenia or neuropathy, or any grade 3 or higher toxicity.

Dr. Sikov reported that 48 patients are evaluable for toxicity and 44 for response. For cycles 1 and 2, the median delivered doses were 75% and 71% of the intended dose, respectively. Thirty-three patients developed grade 3-4 neutropenia, but only two required hospitalization for febrile neutropenia.

Grade 2 and grade 3 neurotoxicities occurred in 12 and 5 patients, respectively. These were primarily peripheral sensory neuropathies. Most patients completed treatment with no serious neurotoxicity, and neurotoxicity did not progress, and in many cases actually improved, in patients who continued treatment following dose reduction.

Response Rates

In metastatic breast cancer, there were no significant differences in response rate between patients with visceral disease and those with soft tissue disease.

In locally advanced breast cancer, responses include 8 of the 11 patients who had inflammatory breast cancer (3 CRs, 5 PRs). Sixteen of 18 responding patients with locally advanced breast cancer were resectable with negative margins. All responding patients are disease-free 3 to 19 or more months after surgery except for one patient who refused axillary dissection, adjuvant chemotherapy, and radiation.

"Weekly high-dose paclitaxel more than doubles the dose intensity delivered with standard every-3-week paclitaxel and achieves response rates comparable to those seen with combination chemotherapy," Dr. Sikov said. The high-dose weekly regimen may yield more rapid responses than the standard schedule, especially in locally advanced disease, he added.

"This is the highest response rate yet reported for single-agent paclitaxel in advanced breast cancer and merits study in a larger group of patients," he concluded.

A planned phase III study in patients with metastatic breast cancer will compare two cycles of paclitaxel at 150 mg/m² weekly for 6 weeks; five cycles of paclitaxel at 175 mg/m² every 3 weeks; and 15 weeks of paclitaxel at 80 mg/m² weekly.