Beta-interferon, retinoids and tamoxifen as maintenance therapy in metastatic breast cancer. A pilot study

Background: Chemotherapy (CT), fundamental for the treatment of metastatic breast cancer (MBC), rarely cures, due to the presence of minimal residual disease (MRD). Based on the synergistic antiproliferative effect of interferon, retinoids and tamoxifen on breast cancer cell lines we designed a pilot study to test if a combination of beta-interferon (β-IFN), retinoids and tamoxifen could improve the progression free survival and overall survival in patients (PTS) treated with CT for MBC. Methods: Thirty-six patients, with stage IV carcinoma of the breast, were treated with a combination of Cyclophosphamide, 5-fluorouracil, 4-epidoxorubicin, vincristine and prednisone every 3 weeks for six courses (FECPV), followed by two courses of methotrexate, mitomycin-c and mitoxantrone (MMM). Treatment was continued, in response, with low dose β-interferon, retynil palmitate and tamoxifen until disease relapse. Results: Among 36 evaluable PTS, 23 achieved a clinical response (64%) (95% c.i. 48 x 80%), 7 had disease stability (19%), and 6 (17%) progressed. Leukopenia occurred in 15 patients, thrombocytopenia in six, and anemia in 11. 16 patients had nausea/vomiting; stomatitis was observed in nine patients and diarrhea in three. Toxicity of maintenance therapy was mild and mainly hepatic. Median response duration was 31 months (range 5-75+). Median overall survival was 32 months (9-83+). Conclusions: Our study shows that this regimen is feasible and shows activity in MBC with an acceptable toxicity.