Doxifluridine as palliative treatment in advanced gastric and pancreatic cancer patients

Background: The association of 5-fluorouracil (5-FU) and leucovorin is currently the most used combination in the treatment of advanced gastrointestinal neoplasms. Doxifluridine (d-FUR) is a fluoropyrimidine derivative that is converted into 5-FU inside tumor cells, where it is selectively cytotoxic. The oral administration of dFUR has been extensively investigated in colorectal carcinoma, and has been proven to be active and well tolerated. The purpose of this study was to test the effectiveness of the oral combination with dFUR plus I-leucovorin in gastric and pancreatic cancer patients. Methods: a total of 50 cases were treated with I-leucovorin 25 mg, followed 2 h later by d-FUR 1,200 mg/m² for 5 days; the cycles were repeated every 10 days. The regimen was given for a maximum of 36 cycles or until disease progression. Twenty-six patients had gastric cancer (all of whom were pretreated with polychemotherapy) and 24 had advanced pancreatic carcinoma. Results: Objective responses were obtained in 4 (15%; 95% CI 1-29) patients with gastric cancer, and in I (4%) with pancreatic cancer. The median response duration was 4 months. All of the responses were seen in patients previously treated with 5-FU-containing regimens. The median survival in gastric cancer patients was 7 months. Toxicity was moderate: WHO grade III and IV diarrhea was observed in 14% of the cases. Conclusions: This study indicates the efficacy of oral d-FUR plus l-leucovorin as palliative treatment in gastric cancer patients. The results in Doxifluridine pancreatic carcinoma are disappointing but are in line with the published data Chemotherapy relating to fluoropyrimidines.