BACKGROUND: The biochemical modulation of 5-fluorouracil (5-FU) by the reduced folate folinic acid (FA) in the treatment of patients with advanced gastric cancer was examined. METHODS: The Southwest Oncology Group performed parallel randomized Phase II trials of two schedules of 5-FU and FA in 80 patients with advanced gastric cancer. Of 76 analyzable patients, 36 were randomized to receive bolus FA (200 mg/m2, days 1-4) along with continuous infusion 5-FU (1000 mg/m2, days 1-4) and 40 were randomized to receive bolus FA (200 mg/m2, days 1-5) before the bolus 5-FU (375 mg/m2, days 1-5). RESULTS: There were three (8%) partial responses (95% confidence interval [CI] 2%-22%) on the continuous infusion arm. The bolus arm had two (5%) complete responses and six (15%) partial responses for an overall response rate of 20% (95% CI 9%-36%). The median duration of response was 4.6 months for the infusion patients and 16.6 months for the bolus patients. Survival was poor, with median survival of 5 months on both regimens. Gastrointestinal toxicity was substantial, with Grade 3 mucositis observed in 36% of patients on the continuous infusion regimen versus only 10% of patients on the bolus regimen. Grade 3 or higher hematologic toxicity occurred more often in the bolus arm than in the continuous infusion arm (28% vs. 14%, respectively). Two toxic deaths occurred, one related to sepsis the other secondary to coronary insufficiency. CONCLUSIONS: Biochemical modulation of 5-FU by FA using the dose and schedules tested has only modest activity in the treatment of advanced gastric cancer.
RCT Entities:
BACKGROUND: The biochemical modulation of 5-fluorouracil (5-FU) by the reduced folatefolinic acid (FA) in the treatment of patients with advanced gastric cancer was examined. METHODS: The Southwest Oncology Group performed parallel randomized Phase II trials of two schedules of 5-FU and FA in 80 patients with advanced gastric cancer. Of 76 analyzable patients, 36 were randomized to receive bolus FA (200 mg/m2, days 1-4) along with continuous infusion 5-FU (1000 mg/m2, days 1-4) and 40 were randomized to receive bolus FA (200 mg/m2, days 1-5) before the bolus 5-FU (375 mg/m2, days 1-5). RESULTS: There were three (8%) partial responses (95% confidence interval [CI] 2%-22%) on the continuous infusion arm. The bolus arm had two (5%) complete responses and six (15%) partial responses for an overall response rate of 20% (95% CI 9%-36%). The median duration of response was 4.6 months for the infusion patients and 16.6 months for the bolus patients. Survival was poor, with median survival of 5 months on both regimens. Gastrointestinal toxicity was substantial, with Grade 3 mucositis observed in 36% of patients on the continuous infusion regimen versus only 10% of patients on the bolus regimen. Grade 3 or higher hematologic toxicity occurred more often in the bolus arm than in the continuous infusion arm (28% vs. 14%, respectively). Two toxic deaths occurred, one related to sepsis the other secondary to coronary insufficiency. CONCLUSIONS: Biochemical modulation of 5-FU by FA using the dose and schedules tested has only modest activity in the treatment of advanced gastric cancer.
Authors: James H Doroshow; Sheryl McCoy; John S Macdonald; Brian F Issell; Taral Patel; Patrick W Cobb; Kathleen J Yost; James L Abbruzzese Journal: Invest New Drugs Date: 2006-11 Impact factor: 3.850
Authors: S Iqbal; B Goldman; C M Fenoglio-Preiser; H J Lenz; W Zhang; K D Danenberg; S I Shibata; C D Blanke Journal: Ann Oncol Date: 2011-03-17 Impact factor: 32.976
Authors: K H Chi; Y Chao; W K Chan; S S Lo; S Y Chen; S H Yen; K Y Chen; C W Wu; S D Lee; W Y Lui Journal: Br J Cancer Date: 1998-06 Impact factor: 7.640