INCREASED INTENSIFICATION AND TOTAL-DOSE OF CYCLOPHOSPHAMIDE IN A DOXORUBICIN-CYCLOPHOSPHAMIDE REGIMEN FOR THE TREATMENT OF PRIMARY BREAST-CANCER - FINDINGS FROM NATIONAL SURGICAL ADJUVANT BREAST AND BOWEL PROJECT B-22

Purpose: The National Surgical Adjuvant Breast and Bowel Project (NSAB P) initiated a randomized trial (B-22) to determine if intensifying bu t maintaining the total dose of cyclophosphamide (Cytoxan, Bristol-Mye rs Squibb Oncology, Princeton, NJ) in a doxorubicin (Adriamycin, pharm acia, Kalamazoo, MI)-cyclophosphamide combination (AC), or if intensif ying and increasing the total dose of cyclophosphamide improves the ou tcome of women with primary breast cancer and positive axillary nodes. Patients and Methods: Patients (N = 2,305) were randomized to receive either four courses of standard AC therapy (group 1); intensified the rapy, in which the same total dose of cyclophosphamide was administere d in two courses (group 2); or intensified and increased therapy, in w hich the total dose of cyclophosphamide was doubled (group 3). The dos e and intensity of doxorubicin were similar in all groups. Disease-fre e survival (DFS) and overall survival were determined using life-table estimates. Results: There was no significant difference in DFS (P = . 30) or overall survival (P = .95) among the groups through 5 years. At 5 years, the DFS of women in group 1 was similar to that of women in group 2 (62% v 60%, respectively; P = .43) and to that of women in gro up 3 (62% v 64%, respectively; P = .59). The 5-year survival of women in group 1 was similar to that of women in group 2 (78% v 77%, respect ively; P = .86) and to that of women in group 3 (78% v 77%, respective ly; P = .82). Grade 4 toxicity increased in groups 2 and 3. Failure to note a difference in outcome among the groups was unrelated to either differences in amount and intensity of cyclophosphamide or to dose de lays and intervals between courses of therapy. Conclusion: Intensifyin g or intensifying and increasing the total dose of cyclophosphamide fa iled to significantly improve either DFS or overall survival in any gr oup. It wets concluded that, outside of a clinical trial, dose-intensi fication of cyclophosphamide in an AC combination represents inappropr iate therapy for women with primary breast cancer. (C) 1997 by America n Society of Clinical Oncology.