EDMONTON, Alberta--Final results of a multicenter phase III trial
show that docetaxel (Taxotere) improves survival more than mitomycin
(Mutamycin)/vinblastine (MV) in anthracycline-resistant advanced
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, 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
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.