Leucovorin Dosing for Gastrointestinal Cancer

What Is the Issue? Since 2008, the shortage of leucovorin has had a significant impact on fluorouracil-based chemotherapy. Many institutions worldwide provided possible options to relieve the leucovorin shortage, including using treatment without leucovorin, lowering the standard leucovorin dose, or using alternative drugs. If lowering the body surface area-adjusted standard dose of leucovorin does not affect efficacy and safety, then implementation of a low flat-dose protocol may prevent mistakes that result during dose calculation and save pharmacy compounding time and costs. Decision-makers want to know if any clinical evidence supports a low flat-dose protocol for leucovorin. What Did We Do? To inform decisions about using flat-dose leucovorin in conjunction with fluorouracil-based chemotherapy, CADTH sought to identify and summarize literature comparing the clinical effectiveness of flat dosing versus weight-based leucovorin dosing. We also attempted to identify evidence-based recommendations for leucovorin dosing for colorectal or upper gastrointestinal cancer. A research information specialist conducted a literature search of the peer-reviewed and grey literature with a search strategy focused on leucovorin, dosing, and colorectal or gastrointestinal cancers. The search was limited to English-language documents published since 2013. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings. What Did We Find? We found 1 small retrospective cohort study (58 patients) comparing low flat-dose 50 mg leucovorin with body surface area-adjusted to high dose 200 mg/m2 to 500 mg/m2 leucovorin in patients with colorectal cancer. The study found no statistically significant differences between the 2 doses in survival or complication rates. We found no evidence-based guidelines regarding leucovorin dosing for colorectal or upper gastrointestinal cancer. However, we found several guidelines with unclear methodology reporting leucovorin doses used in different fluorouracil-based regimens. What Does it Mean? Limited evidence from this review suggests that the standard weight-based dosing of leucovorin may be reduced to a low flat-dose. However, we require a larger and well conducted trial to confirm the findings of that study. Decision-makers may wish to consider that reducing the dose of leucovorin may conserve the supply, reduce pharmacy compounding time and control acquisition costs.