Is levoleucovorin an alternative to racemic leucovorin? A literature review

Our purpose is to perform a comprehensive literature review of the use of levoleucovorin in gastrointestinal malignancies and to assess whether levoleucovorin is a reasonable alternative to racemic leucovorin.

This is an extensive literature review of levoleucovorin use in patients with gastrointestinal tract malignancies. Our review revealed 125 citations with abstracts in the English language, including 16 randomized, controlled trials; 40 case studies; and 69 nonrandomized, controlled trials that included 6 pharmacokinetic (PK)/pharmacodynamic studies with 1 population PK study.

Upon our review, there were 2 randomized controlled trials that directly compared racemic leucovorin with levoleucovorin. Goldberg et al noted that there was no statistically significant difference between time to progression (P = .78) and time to death (P = .57). Furthermore, Scheithauer et al again noted no significant difference in terms of response rates (25% vs. 32%; P = .25), median survival time (15 months vs. 14.5 months; P = .28), overall survival at 1 year (58.3% vs. 60.6%; P = .72), and probability of survival at 2 years (15.3% vs. 23%; P = .16). In addition, multiple other studies, including randomized, controlled; nonrandomized, controlled; and case studies, demonstrate similar efficacy and tolerability between the use of racemic leucovorin or levoleucovorin as a modulator of 5-FU.

In many studies of patients with gastrointestinal malignancies, levoleucovorin has been used interchangeably and solely for racemic leucovorin for 5-FU modulation. Our literature review demonstrates that levoleucovorin has similar efficacy and tolerability when compared with racemic leucovorin, whether used in combination with other chemotherapeutic agents or alone.