EDMONTON, Alberta--Final results of a multicenter phase III trial show that docetaxel(Drug information on docetaxel) (Taxotere) improves survival more than mitomycin(Drug information on mitomycin) (Mutamycin)/vinblastine (MV) in anthracycline-resistant advanced breast cancer.
Jean-Marc Nabholtz, MD, chairman of the Northern Alberta Breast Cancer Program and senior medical oncologist at Cross Cancer Institute, Edmonton, reported the results at ASCO for the International 304 Study Group.
"There is no current standard therapy after anthracycline failure, and thus the therapeutic options are wide open," Dr. Nabholtz pointed out. "Two frequently used options are mitomycin plus vinblastine(Drug information on vinblastine), or one of the taxanes. We compared these two approaches in a nonblinded, randomized, prospective phase III trial."
This trial included 392 patients with metastatic breast cancer progressing despite previous anthracycline chemotherapy. They were randomized either to docetaxel, 100 mg/m², 1 hour IV infusion every 3 weeks (n = 203), or to mitomycin, 12 mg/m², 2- to 5-minute IV infusion every 6 weeks, plus vinblastine, 6 mg/m² bolus injection every 3 weeks (n = 189). The median number of cycles was 6 (range, 1 to 12) for docetaxel vs 4 (range, 1 to 12) for MV.
All patients had failed anthracycline, and 56% were classified as anthracycline resistant. Resistance was defined as having relapsed on adjuvant therapy within 12 months or having had disease progression while on therapy for metastatic breast cancer. Nonresistant patients had progression more than 30 days after chemotherapy for metastatic breast cancer.
Survival Results
With a median follow-up of 18 months, the study showed that docetaxel increased median survival from 8.7 to 11.4 months, time to progression from 11 to 19 months, and overall response rate from 12% to 30%, all statisically significant differences (see Table).
"There was almost a 50% difference in the survival rates for the Taxotere-treated patients, compared to those in the mitomycin/vinblastine group," he said.
Toxicity was manageable and tolerable in both arms. Docetaxel produced significantly more neutropenia (93% vs 63% for MV), while thrombocytopenia was significantly more frequent in the MV arm (12% vs 4% for docetaxel).
Nonhematologic toxicities that were more frequent with docetaxel than MV included infections (11% vs 1%), stomatitis (9% vs 1%), diarrhea (8% vs 0%), and peripheral edema (6% vs 0%), while moderate/severe constipation was more common in the MV arm (12% vs 1% for docetaxel).
Seven toxic deaths occurred, four in the docetaxel group and three in the MV group. Nine patients on docetaxel (4.4%) discontinued treatment because of fluid retention. Ten patients on MV (5.2%) discontinued because of thrombocytopenia.
"Taxotere is more active than mitomycin/vinblastine in the treatment of patients with metastatic breast cancer for whom anthracycline-containing regimens have failed, and the risk-to-benefit ratio favors Taxotere over the combination," Dr. Nabholtz concluded.
