Leucovorin Dosing for Gastrointestinal Cancer

Key Messages

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.