16-WEEK MULTIDRUG REGIMEN VERSUS CYCLOPHOSPHAMIDE, DOXORUBICIN, AND FLUOROURACIL AS ADJUVANT THERAPY FOR NODE-POSITIVE, RECEPTOR-NEGATIVE BREAST-CANCER - AN INTERGROUP STUDY

purpose: The Intergroup conducted this breast cancer adjuvant trial to compare an investigational 16-week regimen with cyclophosphamide, dox orubicin, and fluorouracil (5-FU; CAF). The 16-week regimen features g reater doxorubicin and 5-FU dose-intensity than CAF and improved sched uling of antimetabolites with sequential methotrexate and 5-FU, as wel l as infusion 5-FU. patients and Methods: A total of 646 node-positive , receptor-negative patients were randomly assigned to receive either the 16-week regimen or six cycles of CAF. Breast cancer outcomes inclu ded recurrence as well as disease-free and overall survival. Toxicity was evaluated by the Common Toxicity Criteria (CTC). Treatment-related quality of life was assessed by the Breast Chemotherapy Questionnaire (BCQ) before, during, and 4 months after treatment in 163 patients. T he trial was designed to use one-sided tests of significance for power calculations, but is now reported with both one-sided and the traditi onal two-sided tests of significance. Results: At a median follow-up o f 3.9 years, the estimated 4-year recurrence-free survival rate was 67 .5% with the 16-week regimen versus 62.7% with CAF (P = .19, two-sided ; P = .095, one-sided). The estimated 4-year survival rate wets 78.1% with the 16-week regimen versus 71.4% with CAF (P = .10, two-sided; P = .05, one-sided). CAF produced significantly higher grades of leukope nia, granulocytopenia, and thrombocytopenia, as well as liver and card iac toxicity, whereas the 16-week regimen produced significantly highe r grades of anemia, nausea, stomatitis, and weight loss, as well as sk in and neurotoxicity. There were three treatment-related deaths with C AF but none with the 16-week regimen. During treatment, quality of lif e declined significantly more with the 16-week regimen than CAF, but b y 4 months posttreatment, there was no difference. Conclusion: The 16- week regimen produced marginally better breast cancer outcomes than CA F with similar toxicity but a greater reduction in during-treatment qu ality of life. The 16-week regimen should not be used instead of a sta ndard-dose regimen without careful consideration of the 16-week regime n's pros and cans, which include its complicated schedule. It should p robably not be tested further, but its antimetabolite schedules and fr equent drug administration (ie, dose density) should be considered in the development of new regimens. (C) 1998 by American Society of Clini cal Oncology.