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.
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.