WARSAW, Poland—Results of a multicenter randomized European trial demonstrated the superiority of paclitaxel(Drug information on paclitaxel) (Taxol) and doxorubicin(Drug information on 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(Drug information on fluorouracil) 500 mg/m², doxorubicin 50 mg/m², and cyclophosphamide(Drug information on 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 not allowed.
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.
Study Results
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% complete response).
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.”
