ADJUVANT CHEMOHORMONAL THERAPY WITH CYCLOPHOSPHAMIDE, DOXORUBICIN AND 5-FLUOROURACIL (CAF) WITH OR WITHOUT MEDROXYPROGESTERONE ACETATE FOR NODE-POSITIVE BREAST-CANCER PATIENTS

Background: The Comprehensive Cancer Center trial 82-01 is a prospective randomized study to investigate the value of the addition of high-dose medroxyprogesterone acetate (MPA) to chemotherapy in patients with node-positive operable breast cancer. MPA may be of advantage in this setting because of its activity in estrogen receptor ER-positive as well as ER-negative tumors and since it may protect against chemotherapy-induced myelosuppression and thus enable maintenance of the appropriate chemotherapeutic scheduling. Patients and methods. Four hundred eight evaluable patients with node-positive (N+) operable breast cancer (TI-3, Nl) were entered in a multicenter randomized trial. Two hundred nine patients were randomized in the MPA- arm and 199 in the MPA+ arm. CAF chemotherapy was given as a short i.v. bolus infusion: cyclophosphamide 500 mg/m2 i.V. day 1, doxorubicin 40 mg/M2 i.v. day 1, and 5-fluorouracil 500 mg/m2 i.v. day 1, q 4 wks x 6. MPA was given intramuscularly (i.m.) 500 mg q d x 28 days, followed by 500 mg i.m. twice weekly during 5 months. Results: The main side effects of MPA were weight gain with a mean of 5.5 kg as opposed to 1.8 kg in the control group (p = 0.01) and vaginal bleeding in 30/199 in the MPA+ group and 0 in the MPA- group. MPA ameliorated vomiting grade III, IV (45% vs. 28%, p < 0.001), nausea grade III, IV (50% vs. 34%, p < 0.001) and leucocyte nadir grade III, IV (20% vs. 11%, p = 0.003). Disease-free survival (DFS) after 5 years was 59% in the MPA+ and 49% in the MPA- group (p = 0.12). Patients greater-than-or-equal-to 60 years. benefitted most from MPA treatment, in particular if freedom from distant metastases was taken as the endpoint (p = 0.02). Overall survival (OS) was not significantly different between the two treatment groups (p = 0.18), but within subgroups analysed there was an advantage for MPA+ in patients greater-than-or-equal-to 55 years (p = 0.002) and in pT1 patients (p = 0.045). Conclusions: High-dose MPA ameliorates CAF side effects and reduces the risk of metastatic disease, especially in elderly breast cancer patients.