Clinical Experience with Tegafur and Low Dose Oral Leucovorin: A Dose-Finding Study

Abstract

Tegafur is an effective oral fluoropyrimidine that shows the same activity as 5-fluorouracil for a similar spectrum of cancers. Their biochemical modulation with oral Leucovorin (LV) attempts to simulate treatment with a continuous infusion of 5-fluorouracil and LV with the added advantage of outpatient administration. Thirty-three patients with advanced adenocarcinoma were included in the study. The treatment consisted of tegafur, 0.75 g/m²/day, for 21 days, with oral LV at different dose levels, 15, 30, 45, 60 and 90 mg/day, in a 28-day cycle. A correlation between the LV dose and an increase in grade III/IV toxicity (especially diarrhea, oral mucositis and fatigue) was established in the nonlinear regression model, reaching a plateau at 60 mg of LV. For the tegafur dose used, the recommended dose of LV is in the range of 45-60 mg/ day. This schedule could be considered to evaluate the possible therapeutic effect in phase II trials.

A phase II randomized trial comparing neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in advanced squamous cell carcinoma of the pharynx or larynx

“…To ameliorate emesis and nephrotoxicity, cisplatin at 100 mg/m 2 triweekly was modified to 50 mg/m 2 biweekly, and to ameliorate stomatitis and maintain efficacy, 5-fluorouracil (5-FU) at 1000 mg/m 2 /d through 120-h infusion was replaced with daily oral 5-FU prodrugs (tegafur 800 mg/d or tegafur-uracil at 300 mg/m 2 /d) [12] . According to a dose-finding study investigating toxicity, oral leucovorin at 60 mg/d was used in combination with tegafur for protracted treatment [13] . PUL and PTL combinations had lesser toxicity, particularly for severe stomatitis (5%–7%), and stronger efficacy compared with PF in our patients [14] , [15] .…”

Cisplatin, tegafur, and leucovorin

“…21 To combine with tegafur for protracted treatment, a dose‐finding study for toxicity indicated a dose of oral LV in the range of 45–60 mg per day. 22…”

Open-label trial on efficacy and security of treatment with gemcitabine and oral modulation with tegafur and levofolinic acid (GEMTG) in patients with advanced pancreatic cancer

“…Controlled studies in patients with advanced colorectal cancer showed that FT 1 g/m 2 /day for 21 days had a similar antitumour effi cacy to intravenous 5-FU [7]. In a phase I study, our group investigated the biochemical modulation of FT with oral levofolinic acid (LV) [8]. This combination attempts to simulate the continuous infusion of 5-FU and LV, with the advantage of an ambulant oral treatment.…”