[High-dose leucovorin and 5-FU].

Area of Science:

• Oncology
• Pharmacology
• Cancer Therapeutics

Context:

• Leucovorin (LV) is a folate analog that enhances the efficacy of 5-fluorouracil (5-FU) by stabilizing its binding to thymidylate synthase.
• The combination of LV and 5-FU is a standard treatment for various cancers, with different administration schedules impacting clinical outcomes.
• Previous studies have established response rates for LV and 5-FU combinations in advanced gastric and colorectal cancers.

Purpose:

• To evaluate the clinical efficacy and toxicity of different dosing schedules of leucovorin (LV) in combination with 5-fluorouracil (5-FU) for patients with advanced gastric cancer.
• To compare a weekly high-dose LV schedule with 5-FU against two different 5-day low-dose LV schedules with 5-FU.

Summary:

• A randomized phase II study compared three LV and 5-FU regimens in gastric cancer patients: weekly high-dose LV (250 mg/m2, arm A), 5-day low-dose LV (100 mg/m2, arm B), and 5-day very low-dose LV (10 mg/m2, arm C).
• Arm A achieved a response rate of 33.3%, arm B showed 24.1%, and arm C had no responders.
• All treatment arms reported manageable toxicities, including diarrhea, stomatitis, anorexia, and myelohypoplasia.

Impact:

• High-dose leucovorin combined with 5-FU, particularly using a weekly schedule, appears to be a promising and effective treatment strategy for advanced gastric cancer.
• Low-dose leucovorin (10 mg/m2) in a 5-day schedule demonstrated no significant efficacy in this patient population.
• These findings support the optimization of LV dosing in 5-FU combination therapy for improved gastric cancer treatment outcomes.