THE EFFECT OF ADJUVANT PREDNISONE COMBINED WITH CMF ON PATTERNS OF RELAPSE AND OCCURRENCE OF 2ND MALIGNANCIES IN PATIENTS WITH BREAST-CANCER

Background: The addition of low-dose prednisone (p) to the adjuvant re gimen of cyclophosphamide, methotrexate, 5-fluorouracil (CMF) allowed patients to receive a larger dose of cytotoxics when compared with tho se on CMF alone. However, disease-free survival and overall survival w ere similar for the two groups. To test the hypothesis that low-dose p rednisone might influence the efficacy of the cytotoxic regimen used, the toxicity profiles of the two treatment regimens and the patterns o f treatment failure (relapse, second malignancy, or death) were examin ed. Patients and methods: 491 premenopausal and perimenopausal patient s with one to three positive axillary lymph nodes included in Internat ional (Ludwig) Breast Cancer Study Group (IBCSG) trial I from 1978 to 1981 and randomized to receive CMF or CMFp were analyzed for differenc es in long-term outcome and toxic events. The 250 patients assigned to CMF and prednisone received on the average 12% more cytotoxic drugs t han those who received CMF alone. Results: The 13-year DFS for the CMF p group was 49% as compared to 52% for CMF alone, and the respective O S percents were 59% and 65%. Several toxic effects such as leukopenia, alopecia, mucositis and induced amenorrhea were reported at a similar incidence in the two treatment groups. Using cumulative incidence met hodology for competing risks, we detected a statistically significant increase in first relapse in the skeleton for the CMFp, group at 13 ye ars follow-up with a relative risk (RR) of 2.06 [95% confidence interv al (CI), 1.23 to 3.46; P = 0.004]. Patients with larger tumors in the CMFp regimen were especially subject to this increase with a RR for fa ilure in the skeleton of 3.32 (95% CI, 1.57 to 7.02; P = 0.0005). CMFp -treated patients also had a larger proportion of second malignancies (not breast cancer), with RR of 3.34 (95% CI, 0.91 to 12.31; P = 0.09) . Conclusions: Low-dose continuous prednisone added to adjuvant CMF ch emotherapy enabled the use of higher doses of cytotoxics. This increas ed dose had no beneficial effect on treatment outcome, but was associa ted with an increased risk for bone relapses and a small, not statisti cally significant increased incidence of second malignancies. The effe cts of steroids, which are widely used as antiemetics (oral or pulse i njection) together with cytotoxics, should be investigated to identify their influence upon treatment outcome.