Paclitaxel (T) following doxorubicin/cyclophosphamide (AC) as adjuvant chemotherapy for node-positive breast cancer: Results from NSABP B-28

Category: Adjuvant Therapy

Authors: E. P. Mamounas, J. Bryant, B. C. Lembersky, B. Fisher, J. N. Atkins, L. Fehrenbacher, P. C. Raich, G. Yothers, A. Soran, N. Wolmark; NSABP Operations and Biostatistical Center, Pittsburgh, PA


Abstract:The primary aim of NSABP B-28 was to determine whether 4 cycles of adjuvant T (225 mg/m² as a 3-hour infusion) given following 4 cycles of adjuvant AC (60/600 mg/m²) (AC->T) will prolong overall survival (OS) and disease-free survival (DFS) when compared to 4 cycles of AC alone, in patients (pts) with resected operable breast cancer and histologically positive axillary nodes. Between 8/95 and 5/98, 3060 pts were randomized. All pts ≥ 50 years and those < 50 with ER-or PgR-positive tumors also received tamoxifen 20 mg p.o. daily for 5 years, starting with AC. Lumpectomy pts received breast irradiation following chemotherapy. Pt and tumor characteristics were well balanced between treatment groups; age < 50: 51%, 50-59: 31%, ≥ 60: 19%; clinical tumor size ≤ 2.0 cm: 59%, 2.1-4.0 cm: 32%, > 4.0 cm: 8%; positive nodes 1-3: 70%, 4-9: 26%, ≥ 10: 4%; ER-positive: 66%, PgR-positive: 61%; tamoxifen was given in 84%; 98% of pts completed all 4 cycles of AC. Of pts randomized to AC->T, 90% received ≥ 1 cycle of T and 75% received all 4. Grade 3+ toxicity: 28% of pts during AC and 34% during T. Most frequently reported grade 3+ toxicity on AC (% of pts): day 1 granulocytopenia: 8%, febrile neutropenia: 7%, nausea: 6%, vomiting: 5%, infection: 3%, thromboembolic events: 2% and stomatitis: 2%. Most frequently reported grade 3+ toxicities on T (% of pts): neurotoxicity: 19%, arthralgia/myalgia: 11%, day 1 granulocytopenia: 4%, febrile neutropenia: 2%, infection: 2%, thromboembolic events: 2% and hypersensitivity reactions: 1%. As of 12/18/02, 472 deaths and 827 events have been reported. Per protocol, definitive analysis is scheduled following report of the 490^th death (80% power to detect a 22.6% decrease in mortality rate). This will occur by closure of the 3/31/03 summary file (median follow-up 67 months). This file will be used for definitive analysis and results will be presented at the meeting. (Supported by Public Health Service Grant U10-CA12027 and U10-CA69651).