Impact of Leucovorin Shortage: A Comparison of Standard-Dose Versus Reduced-Dose Leucovorin in Metastatic Colorectal Cancer.

Abstract

The frequent global shortage of leucovorin has raised several concerns. A guided approach is lacking in the guidelines. Data comparing standard-dose (400 mg/m²) and reduced-dose (200 mg/m²) leucovorin, both administered once on day 1 of each cycle, are unavailable. We plan to assess the efficacy and safety of leucovorin-containing regimens for standard and reduced doses in metastatic colorectal cancer (mCRC). This retrospective/prospective observational study was conducted at a tertiary hospital in Saudi Arabia and included data from 2020 to 2025. Adults with mCRC treated with a leucovorin-containing regimen were included. Because of frequent leucovorin shortages, the dose was reduced to 200 mg/m² intravenously given once on day 1 of each cycle. Patients were divided into two groups: leucovorin-400 and leucovorin-200. The study end points were progression-free survival (PFS), response rate, overall survival (OS), and safety. A total of 99 patients were included (50 in the leucovorin-200 group and 49 in the leucovorin-400 group). The FOLFOX6 protocol was given to 67.3% of the overall population. The median PFS was 8 months for the leucovorin-200 group (95% CI, 5.8 to 12.6) and 8.1 months for the leucovorin-400 group (95% CI, 3.9 to 16.3; <i>P</i> = .943). Regarding response, 69.3% progressed with leucovorin-400 and 64% with leucovorin-200. The median OS was 71 months in the leucovorin-200 group and was not reached in the leucovorin-400 group (<i>P</i> = .336). The incidence of adverse events was similar between the two groups except for grade 1 diarrhea, which occurred in 51% with leucovorin-400 and 18.4% with leucovorin-200 (<i>P</i> = .001). A total of 1,180 vials were spared after changing the protocol, which correlates with 62,699 Saudi Riyal spared. The choice between standard-dose and reduced-dose leucovorin may not affect outcomes in the metastatic setting. The reduced dose is a reasonable alternative in cases of drug shortage.