POSTSURGICAL ADJUVANT CHEMOTHERAPY OF STAGE-II BREAST-CARCINOMA WITH OR WITHOUT CROSSOVER TO A NON-CROSS-RESISTANT REGIMEN - A CANCER AND LEUKEMIA GROUP-B STUDY

Purpose: To compare two cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) regimens with a doxorubicin-based regimen-vinblastine, doxorubicin, thiotepa, and Halotestin (Upjohn, Ka lamazoo, MI) (VATH)-in patients with stage II node-positive breast car cinoma. Methods: Nine hundred forty-five women were treated with a 6-w eek induction course of CMFVP. They were then randomized to receive on e of two consolidation CMFVP regimens: 6-week courses or 2-week course s. Following completion of CMFVP consolidation, patients were again ra ndomized to either continue the CMFVP regimen or to receive six escala ting doses of VATH. Results: Among all patients, with a median follow- up time of 11.5 years, there is no statistically significant differenc e in disease-free survival (DFS) between the two consolidation CMFVP r egimens, VATH intensification treatment is statistically significantly superior to CMFVP in terms of DFS (P = .0040), For patients with one to three involved nodes, there is currently no significant difference between VATH and CMFVP; however, among those with four or more positiv e lymph nodes, there is a significant difference in favor of VATH (P = .0037). There is also improved overall survival with VATH (P = .043; median, > 14 years v 10 years), This difference is also statistically significant in patients with four or more involved lymph nodes, among postmenopausal patients, and among postmenopausal estrogen receptor-po sitive patients. Conclusion: Chemotherapy with crossover to escalating dose of VATH following CMFVP was well tolerated and effective, Inaugu ration of VATH as a treatment intensification at the eighth month prod uced a major increase in relapse-free and overall survival, The observ ation that sensitivity to VATH is retained 50 long after mastectomy ra ises questions about the proper duration of adjuvant chemotherapy and lends support to further investigation of crossover designs in future trials of postoperative adjuvant chemotherapy regimens. (C) 1996 by Am erican Society of Clinical Oncology.