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A Prospective, Randomized Comparison of Two Doses of Combination Alkyating Agents (AA) as Consolidation After CAF in High-Risk Primary Breast Cancer Involving Ten or More Axillary Lymph Nodes (LN): Preliminary Results of CALGB 9082/SWOG 9114/NCIC MA-13.

William P. Peters, M.D., Ph.D., G.L. Rosner, D. Hurd, L. Norton, R. Schilsky

Despite conventional dose chemotherapy, the prognosis remains poor for primary breast cancer patients with multiple involved axillary lymph nodes. Between January 1991 and May 1998, we treated 874 women with Stage II or IIIA breast cancer involving ten or more axillary lymph nodes in a prospective, randomized study evaluating intensive alkyating agents (AA) consolidation after CAF. The median age of the patients was 45 (range 22 to 66), the median tumor size was 3.05 cm, and the median number of involved lymph nodes was 14 (range 10 to 52). Nineteen percent of the patients had more than 20 involved lymph nodes, and 69 percent were hormone receptor (HR)-positive.

Eligible patients were treated with four cycles of CAF (600/60/1200 mg/M² q 28 days). Ninety-nine of the patients who were entered were not randomized, including 24 for recurrent breast cancer, 2 who died of CAF toxicity, 26 denied insurance coverage, 17 who withdrew, 13 who were ineligible, and 7 others. Of those remaining, 394 were randomized to high-dose CPB (HDCPB: cyclophosphamide [5625 mg/M² ], cisplatin [165 mg/M² ], and BCNU [600 mg/M² ], with BM and PBPC support), and 391 to intermediate dose CPB (IDCPB: C: 900 mg/M² , P: 90 mg/M² , and B: 90 mg/M² ), with G/CSF support. Patients relapsing on intermediate dose CPB were eligible for subsequent ABMT. All patients were planned for local-regional radiotherapy, and HR-positive patients received tamoxifen for 5 years.

An early outcome analysis was performed in 1998 with only 60 percent of the expected number of events, which appeared at the median followup of 37 months. The intent-to-treat EFS and OS comparisons between high dose and intermediate dose CPB were inconclusive (68 percent versus 64 percent, p=0.7; 78 percent versus 80 percent, p=0.1, log rank test).

Therapy-related events were concentrated in the first year, and there was a reduction in relapses and a trend in age-related toxicity. We will provide updated followup on this study. Although additional studies are required to resolve the role of high-dose consolidation therapy in this setting, the information reported here may be of value to women evaluating treatment options.