title: Interferon-beta, retinoids, and tamoxifen in the treatment of metastatic breast cancer: a phase II study.
abstract: Based on the additive or synergistic antiproliferative effect of interferon and tamoxifen on breast cancer cell lines and on preclinical and clinical data on retinoids alone and in combination with antiestrogen or interferon, we designed a pilot phase II study to test the toxicity of simultaneous administration of interferon-beta (IFN-beta), retinoids (R), and tamoxifen (TAM) and the efficacy of this combination as salvage therapy in a group of patients with metastatic breast cancer (MBC). A total of 49 stage IV breast cancer patients, 11 pretreated with hormones, 26 with chemotherapy, and 12 with both, received 30 mg TAM and two dose levels of IFN-beta and retinyl palmitate. Among 49 evaluable patients, 27 achieved a clinical response (55%; 95% CI 41-69%), 10 had stable disease (20%), and in 12 (25%) the disease progressed. Toxicity with both dose levels was moderate and mainly hepatic. Median response duration, not statistically different in estrogen receptor-positive and negative patients, was 31.4 months (range 4.9-67). Median overall survival was 19.2 months (range 2-69). We have shown that long-term administration of TAM, IFN-beta, and retinyl palmitate is feasible with moderate toxicity. We have also demonstrated that this regimen is active in pretreated MBC patients and that responses are not influenced by receptor status.
authors.affiliation: Division of Internal Medicine (Oncology Unit), Civil Hospital, Avezzano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Recchia
authors.forename: G
authors.initials: G
authors.lastname: Sica
authors.forename: S
authors.initials: S
authors.lastname: de Filippis
authors.forename: S
authors.initials: S
authors.lastname: Discepoli
authors.forename: S
authors.initials: S
authors.lastname: Rea
authors.forename: P
authors.initials: P
authors.lastname: Torchio
authors.forename: L
authors.initials: L
authors.lastname: Frati
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003131:Combined Modality Therapy; D004224:Diterpenes; D004357:Drug Synergism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016899:Interferon-beta / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010865:Pilot Projects; D000084562:Retinyl Esters; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use; D014801:Vitamin A / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D016588:Anticarcinogenic Agents; D004224:Diterpenes; D000084562:Retinyl Esters; D013629:Tamoxifen; D014801:Vitamin A; C014794:retinol palmitate; D016899:Interferon-beta