Phase II trial of uracil tegafur (UFT) plus leucovorin in patients with advanced hepatocellular carcinoma

Although UFT 300 mg/m(2)/day and leucovorin 90 mg/day administered orally i n divided doses administered every 8 hours for 28 days repeated every 35 da ys could be administered safely to patients with advanced hepatomas and goo d performance status, this combination and schedule has limited activity in treating advanced hepatoma. Background/purpose: Biochemical modulation of 5-fluorouracil has yielded hi gher response rates in hepatoma when compared to treatment with 5-fluoroura cil as a single agent, although the impact on survival has been negligible. This study was conducted to determine the activity and evaluate the toxici ty of uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-M yers Squibb, Wallingford, CT) plus oral calcium leucovorin in the treatment of patients with advanced hepatocellular carcinoma (hepatoma). Patients and methods: Sixteen patients with advanced measurable hepatocellu lar carcinoma were enrolled onto the trial. All patients had a Karnofski pe rformance status greater than or equal to 60%, platelet count greater than or equal to 75,000/mu L, total bilirubin less than or equal to 2.0 x instit utional upper limit of normal but otherwise normal liver and kidney functio n profile and bidimensionally measurable disease by CT or ultrasound examin ation. None of these patients received prior cytotoxic chemotherapy or radi ation therapy for advanced disease. Fourteen patients received 300 mg/m(2)/ d UFT plus 90 mg/d leucovorin administered orally in divided daily doses ev ery 8 hours for 28 days repeated every 35 days. Two patients registered for the trial but did not receive study medication. Objective tumor response, the primary purpose of this trial, was evaluated after two courses of thera py. Other end-points included toxicity, time to progression, and overall su rvival. Results: Fourteen patients were evaluable for response and toxicity, respec tively. No complete or partial responders were observed in this trial. Thre e patients had stable disease lasting 17 to 22 weeks. Toxicity was mild wit h severe (grade 3 or 4) liver pain, diarrhea, anorexia/nausea, fatigue, dys pnea, hyperbilirubinemia, anemia, and edema seen in 3 (21%), 2 (14%), 3 (21 %), 2 (14%), 1 (7%), 1 (7%), 1 (7%) and 1(7%) patients, respectively. The m ost frequent grade 1 and 2 toxic effects included fever of unknown origin, dyspnea, nausea, vomiting and diarrhea. Conclusion: UFT 300 mg/m(2)/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate antitumor activity against advanced hepatomas. Further treatment using this regimen is not recommended for this disease.