Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced pancreatic carcinoma: A University of Chicago phase II consortium study

Background/objectives: Uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) has broad anti-tumor activity for cancers arising from the gastrointestinal tract. However, there are no published data regarding the efficacy of leucovorin-modulated UFT in patients with pancreatic cancer. The objective of this trial was to determine the activity and evaluate the toxicity of UFT plus oral calcium leucovorin in patients with advanced pancreatic adenocarcinoma. Patients and methods: Fourteen patients with advanced measurable adenocarcinoma of the pancreas were enrolled onto the trial. Patients received 300 mg/m²/d UFT plus 90 mg/d leucovorin administered orally in divided doses every eight hours for 28 days repeated every 35 days. Objective tumor response was evaluated after two courses of therapy. Results: Fourteen patients were evaluable for response and toxicity. No objective responses were seen. The median (range) time to progression and survival were 14 (1.6-37), and 15 (1.9- 62) weeks, respectively. Toxicity was mild with severe (grade 3 or 4)hyperbilirubinemia, pain, diarrhea, transaminitis, venous thrombus, weakness, renal failure, confusion, and edema/ascites seen in three (21%), one (7%), two (14%), one (7%), one (7%), one (7%), one (7%), one (7%), and two (14%) patients, respectively. Conclusion: In the 14 patients evaluable, UFT 300 mg/m²/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate anti-tumor activity against advanced pancreatic adenocarcinoma; however, this oral regimen was well tolerated and devoid of neutropenia, significant oral mucositis or diarrhea.