A fixed-ratio combination of uracil and ftorafur (UFT) with low dose leucovorin. An active oral regimen for advanced colorectal cancer

Abstract

Background. UFT is a fixed‐ratio combination of uracil and Ftorafur, a prodrug that is absorbed orally and metabolized in vivo to 5‐fluorouracil (5‐FU). Uracil potentiates 5‐FU through interference with its catabolism. The combination of UFT and leucovorin in patients with advanced incurable colorectal cancer, to evaluate preliminary activity and toxicity in this patient population. Methods. Twenty‐one patients were treated. Twenty patients were evaluable for toxicity and response. Patients received UFT 350 mg/m2/day divided every 8 hours. Patients took a 5 mg tablet of leucovorin every 8 hours, concurrent with each UFT dose. Treatment was continued for 28 consecutive days, followed by a 7‐day rest. Results. Five major objective responses (one complete and four partial) were observed. Toxicity was mild, with no dose‐limiting myelosuppression. Four patients experienced grade 3 diarrhea or higher, and two patients experienced dose‐limiting mucositis. Conclusion. UFT and low dose leucovorin is a well tolerated, orally administered regimen with activity in colorectal cancer. A randomized comparison of this regimen with conventional parenteral regimens is warranted. Cancer 1995;75:782‐5.

Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study

“…It is difficult to explain why survival in stage III was poor with UFT monotherapy; it might be explained by the difference in dose intensity of UFT. Tegafur/uracil was administered at a dosage of 600 mg body À1 in three divided doses daily (Malik et al, 1990) or 300 or 350 mg m À2 day À1 with LV (Saltz et al, 1995) in metastatic colorectal cancer. Our dose of UFT was less than that in those studies, despite the absence of LV modulation.…”

“…Tegafur is an orally bioavailable prodrug of 5-FU, and uracil reversibly inhibits the primary catabolic enzyme for 5-FU, namely dihydropyrimidine dehydrogenase. Phase I/II studies of advanced or metastatic colorectal cancer treated with different regimens of UFT and LV achieved excellent response rates and had favourable toxicity (Saltz et al, 1995;Feliu et al, 1997;Rustum, 1997). In phase III, oral UFT/LV provided a safer, more convenient oral alternative to a standard bolus i.v.…”

Weekly irinotecan plus UFT and leucovorin as first-line chemotherapy of patients with advanced colorectal cancer

“…The antitumor activity of UFT increased when combined with oral LV [21][22][23][24][25][26][27][28]. Two large phase III studies conducted in patients with previously untreated metastatic CRC showed that oral UFT/LV has equivalent antitumor efficacy and a significantly more favorable safety profile than i.v.…”

Comparison of adjuvant FOLFOX4 chemotherapy and oral UFUR/LV following adjuvant FOLFOX4 chemotherapy in?patients with stage?III colon cancer subsequent to radical resection

“…In 2000, a randomized comparison of the relative efficacies of 5-FU plus LV and UFUR plus LV in 1,530 evaluable patients indicated that the two regimens have similar toxicity profiles (28). Evidence that UFUR plus oral LV is associated with significant antitumor activity and has a well-tolerated toxicity makes this a logical formulation for the adjuvant treatment of colon cancer (29)(30)(31). Since UFUR can be taken orally, patients receiving oral UFUR therapy are not required to stay in hospital for long periods (27).…”