ABSTRACT
Because of the poor response of pancreatic cancer to conventional therapy, the authors performed a phase II pilot study to evaluate whether beta-interferon and retinoids, added to active chemotherapeutic agents, could increase response rate and survival in a group of patients who had metastatic disease. Twenty-three chemotherapy-naive patients were treated as follows: epirubicin, 60 mg/m2, and mitomycin C, 10 mg/m2, intravenously on day 1; folinic acid, 200 mg/m2, and 5-fluorouracil (5-FU), 370 mg/m2, intravenously for 5 consecutive days. beta-Interferon, 1 x 10(6) IU/m2, subcutaneously three times a week, and retinol palmitate, 50,000 IU orally twice a day, were given between chemotherapy cycles. Patients having responses and disease stabilization were maintained with the same dose of beta-interferon and retinol palmitate. Treatment was given every 4 weeks for four courses or until onset of progression. A median of three courses of chemotherapy was delivered to each patient. All patients were evaluable. Eight patients responded (35%) and 8 (35%) had stable disease. Median time to progression and survival for all patients were, respectively, 6.1 months and 11 months. Toxicity was severe: 60% of patients had hematologic toxicity, 40% had gastrointestinal toxicity, 13% had cardiac toxicity, and 1 patient had a hemolitic-uremic syndrome. The combination of chemotherapy, beta-interferon, and retinoids shows activity in metastatic pancreatic carcinoma. Toxicity was high but patients who had responses and disease stabilization had prolonged symptom palliation.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Interferon-beta/administration & dosage , Pancreatic Neoplasms/drug therapy , Vitamin A/analogs & derivatives , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adult , Aged , Diterpenes , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Mitomycin/administration & dosage , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/secondary , Retinyl Esters , Survival Rate , Vitamin A/administration & dosageABSTRACT
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 (beta-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 Cyclophosfamide, 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 beta-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.
