A weekly dose of paclitaxel prolongs overall survival of breast cancer patients more effectively than weekly docetaxel or the standard 3-week schedule for either taxane, according to investigators of a randomized trial comparing these adjuvant regimens in nearly 5,000 women.
Weekly paclitaxel (Taxol) and docetaxel (Taxotere) every 3 weeks were associated with better 5-year disease-free survival than was the standard paclitaxel regimen, with odds ratios of 1.27 (P = .0006) and 1.23 (P = .02), respectively, the investigators reported (N. Engl. J. Med. 2008:358;1663-71).
Only weekly paclitaxel produced significantly longer overall survival (OR 1.32, P = .01), however. The 32% reduction in the hazard ratio for death, the authors noted, is comparable to that seen with anthracycline-based chemotherapy in the absence of adjuvant cytotoxic therapy.
“The take-home message is that paclitaxel is effective for tumors that are hormone receptor positive and HER2 negative, which accounts for about two-thirds of all breast cancer,” lead investigator Dr. Joseph A. Sparano of Montefiore Medical Center, New York, said in an interview.
These types of tumors were present in 70% and 19% of the women in the trial, respectively. “This is important,” Dr. Sparano said, “because a recent study suggested that those patients may not benefit from paclitaxel therapy.”
The finding that “the most effective way to administer paclitaxel was on a weekly basis over 12 consecutive weeks” was also clinically significant. This allows treatment to be completed in a shorter period, which is an advantage.
“What was somewhat surprising was that we didn't see a similar benefit for weekly docetaxel,” Dr. Sparano said. This may be attributable to higher toxicity and poorer patient compliance with this regimen.
Moderate to severe neuropathy was observed in 27% of the patients receiving weekly paclitaxel vs. 20% of women given paclitaxel every 3 weeks and 16% of women on either docetaxel regimen. Otherwise, overall grade 3/4 adverse events with weekly paclitaxel were comparable to those with standard dosing and lower than with either docetaxel schedule.
Four cooperative research groups collaborated on the trial, which was led by investigators from the Eastern Cooperative Oncology Group. The study followed 4,950 women who had lymph node-positive or high-risk lymph node-negative breast cancer for a median of 63.8 months.
The standard of care for these patients was completion of chemotherapy followed by a taxane given every 3 weeks. The most effective taxane and dosing schedule had not been established, however.
All women in the trial received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks for four cycles. They were then randomized to receive treatment with paclitaxel (175 mg/m2) or docetaxel (100 mg/m2) every 3 weeks for four cycles or weekly paclitaxel (80 mg/m2) or weekly docetaxel (35 mg/m2) for 12 weeks.
According to Dr. Sparano, an ongoing trial (SO221) is addressing the next logical question, comparing weekly and every-2-week paclitaxel schedules in women with hormone receptor-positive and HER2-negative breast cancer.
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