| Abstract: | BACKGROUND:: The addition of low-dose prednisone (p) to the adjuvant regimenof cyclophosphamide, methotrexate, 5-fluorouracil (CMF) allowedpatients to receive a larger dose of cytotoxics when comparedwith those on CMF alone. However, disease-free survival andoverall survival were similar for the two groups. To test thehypothesis that low-dose prednisone might influence the efficacyof the cytotoxic regimen used, the toxicity profiles of thetwo treatment regimens and the patterns of treatment failure(relapse, second malignancy, or death) were examined. PATIENTS AND METHODS:: 491 premenopausal and perimenopausal patients with one to threepositive axillary lymph nodes included in International (Ludwig)Breast Cancer Study Group (IBCSG) trial I from 1978 to 1981and randomized to receive CMFp or CMFp were analyzed for differencesin long-term outcome and toxic events. The 250 patients assignedto CMF and prednisone received on the average 12% more cytotoxicdrugs than those who received CMF alone. RESULTS:: The 13-year DFS for the CMFp group was 49% as compared to 52%for CMF alone, and the respective OS percents were 59% and 65%.Several toxic effects such as leukopenia, alopecia, mucositisand induced amenorrhea were reported at a similar incidencein the two treatment groups. Using cumulative incidence methodologyfor competing risks, we detected a statistically significantincrease in first relapse in the skeleton for the CMFp groupat 13 years follow-up with a relative risk (RR) of 2.06 confidenceinterval (CI), 1.23 to 3.46; P = 0.004]. Patients with largertumors in the CMFp regimen were especially subject to this increasewith a RR for failure in the skeleton of 3.32 (95% CI, 1.57to 7.02; P = 0.0005). CMFp-treated patients also had a largerproportion of second malignancies (not breast cancer), withRR of 3.34(95% CI, 0.91 to 12.31; P = 0.09). CONCLUSIONS:: Low-dose continuous prednisone added to adjuvant CMF chemotherapyenabled the use of higher doses of cytotoxics. This increaseddose had no beneficial effect on treatment outcome, but wasassociated with an increased risk for bone relapses and a small,not statistically significant increased incidence of secondmalignancies. The effects of steroids, which are widely usedas antiemetics (oral or pulse injection) together with cytotoxics,should be investigated to identify their influence upon treatmentoutcome. adjuvant therapy, breast cancer, CMF, patterns of relapse, prednisone, secondary neoplasm |
