TREATMENT OF ADVANCED ADENOCARCINOMAS OF THE EXOCRINE PANCREAS AND THE GALLBLADDER WITH 5-FLUOROURACIL, HIGH-DOSE LEVOFOLINIC ACID AND ORALHYDROXYUREA ON A WEEKLY SCHEDULE - RESULTS OF A MULTICENTER STUDY OF THE SOUTHERN-ITALY-ONCOLOGY-GROUP (GOIM)

BACKGROUND. To date there is no established chemotherapeutic treatment for patients with unresectable locally advanced and/or metastatic car cinomas of the exocrine pancreas or the gallbladder. A multicenter Pha se II trial has been performed by the Southern Italy Oncology Group wi th the aim of evaluating the clinical effectiveness and tolerability o f weekly 5-fluorouracil (5-FU) in modulation with intravenous (i.v.) h igh dose levofolinic acid and oral hydroxyurea. METHODS. A total of 70 patients fulfilling the standard eligibility for a Phase II study wer e enrolled in the trial. Forty patients had advanced pancreatic adenoc arcinoma and 30 had advanced gallbladder carcinoma. The treatment sche dule was: levofolinic acid, 100 mg/m(2), in 500 mL of normal saline ov er 2-hour infusion followed by 5-FU, 600 mg/m(2) i.v, bolus, and oral hydroxyurea, 1000 mg/m(2), for 1 day every week for 6 consecutive week s followed by 15 days of rest. RESULTS. Among the 40 patients with pan creatic adenocarcinoma, 5 (12.5%; 95% confidence level [CL], 8.5-16.5% ) showed a partial response with a median duration of 5.6+ months, and 13 had stable disease. Twenty-two patients progressed. Median surviva l was 5.8 months. Among patients with advanced gallbladder carcinoma, 9 of 30 had a partial response (30%; 95% CL, 26-34%) with a median dur ation of 6.5 months, and 8 (27%) had stabilization of disease. Thirtee n patients showed progressive disease. Median overall survival was 8 m onths. Toxicity was mild, with Grade 1 to 2 leukopenia and gastrointes tinal toxicity the most frequent side effects. No chemotherapy-related deaths were observed. CONCLUSIONS. 5-FU in modulation with i.v. levof olinic acid and oral hydroxyurea on a weekly schedule is well tolerate d by the vast majority of patients with locally advanced and/or metast atic carcinoma of the pancreas or the gallbladder. Although response r ate and overall survival for patients with pancreatic adenocarcinoma a re far from acceptable, the 30% overall response rate achieved in pati ents with advanced gallbladder carcinoma suggests that 5-FU in modulat ion with levofolinic acid and hydroxyurea is active in this neoplasm, The combination of modulated 5-FU with other antineoplastic drugs seem s worthy of clinical testing in further controlled trials. (C) 1995 Am erican Cancer Society.