Phase II Trial of a Doxorubicin/Docetaxel Doublet for Locally Advanced and Metastatic Breast Cancer: Results from National Surgical Adjuvant Breast and Bowel Project Trial BP-57

Abstract

A phase II trial at 12 institutions using AT (doxorubicin 60 mg/m 2 plus docetaxel 60 mg/m 2) given every 21 days was conducted. Eighty-nine patients were entered who ranged in age from 25 to 75 years, 41.6% of whom had stage IIIB disease and 58.4% of whom had stage IV disease. Among the patients with stage IV disease, 32.7% had received prior adjuvant chemotherapy. Premedication with dexamethasone (8 mg orally twice per day for 3 days) and prophylactic ciprofloxacin (500 mg orally twice per day on days 5-15) was used. Colony-stimulating growth factors were reserved for secondary prophylaxis after prolonged or febrile neutropenia (FN) or documented severe infection in an earlier cycle. After a cumulative dose of doxorubicin of 480 mg/m 2, patients could continue to receive docetaxel (100 mg/m 2) alone. Median time on study as of July 6, 2003, was 54 months. Febrile neutropenia occurred in 36 patients (41.9%): 23 developed FN in the absence of previous prophylactic growth factor support and 13 developed it despite previous growth factor support. One patient died from sepsis. Other grade 3/4 adverse events included nausea in 3.5%, vomiting in 4.7%, stomatitis in 8.1%, diarrhea in 5.8%, arthralgia/myalgia in 2.3%, fluid retention in 1.2%, pulmonary embolism in 1.2%, rest dyspnea in 1.2%, neuromotory toxicity in 1.2%, and neurosensory toxicity in 1.2%. Clinical congestive heart failure was seen in 2 patients (2.3%). Sixty-seven patients were evaluable for best response with 6 cycles of therapy. Fourteen patients (20.9%) had a complete response and 30 (44.8%) had a partial response, for an overall response rate of 65.7% in evaluable patients. The median response duration was 25.9 months, and the median time from entry to progression or death was 27.5 months. The median survival time for the 86 patients with endpoint information was 31.1 months. The administration of AT with primary ciprofloxacin and secondary colony-stimulating factor prophylaxis is feasible, and the combination is active. Its value in the adjuvant setting is currently under investigation.