WARSAW, PolandResults of a multicenter randomized European
trial demonstrated the superiority of paclitaxel (Taxol) and
doxorubicin (Adriamycin) (AT) over standard FAC chemotherapy as
first-line treatment for metastatic breast cancer.
Historically, FAC has produced a response rate of 55% to 60% in
patients with metastatic breast cancer, said Tadeusz
Pienkowski, MD, PhD, an oncologist at the Maria Sklodowska-Curie
Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
We wanted to see whether that response rate could be improved
by use of taxane-based combination chemotherapy.
Investigators randomized 267 patients to two treatment regimens. The
AT regimen consisted of doxorubicin at a dose of 50 mg/m² given
on day 1 and pac-litaxel at a dose of 220 mg/m² given on day 2,
with doses repeated every 3 weeks for a total of eight courses of therapy.
FAC consisted of fluorouracil 500 mg/m², doxorubicin 50
mg/m², and cyclophosphamide 500 mg/m², also given every 3
weeks for a total of eight cycles.
The trial design excluded patients who had received prior
chemotherapy for metastatic breast cancer, but about half the
patients had received adjuvant chemotherapy, and a quarter had
received endocrine treatment. Prior anthracyclines or taxanes were
A total of 259 patients were evaluable for response. The median age
of the patients was 50. There were no differences between the two
groups in prior therapy; 44% of patients in the AT arm had received
prior adjuvant therapy, as had 46% in the FAC arm. The study
treatment was first-line therapy for 27% of patients.
At the time of analysis, 196 patients had experienced tumor
progression. The AT regimen significantly increased the median time
to progression, 8.3 months vs 6.2 months with FAC (P = .034) (see Table).
At a median of 24 months of follow-up, median survival was 23 months
with AT and 18.3 months with FAC (P = .006). The overall response
rate was 68% with AT (19% complete response) vs 55% with FAC (8%
Neutropenia occurred in virtually all patients in both groups, but
the incidence of grade 3-4 neutropenia was significantly higher with
AT, 89% compared to 65% for FAC (P = .008). The incidence of severe
infections and febrile neutropenia did not differ between the two
groups (8% with AT and 5% with FAC). Diarrhea and arthralgia occurred
more often with AT, while nausea/vomiting was more common in the FAC group.
Cardiotoxicity also did not differ between the two groups,
Dr. Pienkowski said. One patient in the FAC group developed severe
congestive heart failure (CHF) during the study. Two patients who had
received AT developed CHF (grade 1 and grade 3) during follow-up.
The incidence rate of CHF associated with AT is 1.5, he said.
Dr. Pienkowski concluded that doxorubicin/paclitaxel is an
effective regimen showing a statistically significant advantage over
FAC in time to progression, response rate, and overall survival.