High- versus low-dose leucovorin in the FOLFOX regimen for metastatic colorectal cancer (mCRC).

Abstract

e14583 Background: In response to the national leucovorin shortage in 2008, our institution adjusted the FOLFOX6 (5-FU, leucovorin, and oxaliplatin) protocol to utilize a lower-dose of leucovorin (20mg/m2). This decision was based on limited prospective studies suggesting lower doses of leucovorin may be equally effective in 5-FU containing regimens. This retrospective study evaluates outcomes in mCRC patients treated with low (20mg/m2) vs. standard high dose (400mg/m2) leucovorin in the FOLFOX regimen for mCRC. Methods: Consecutive patients from 2004 to 2011 treated at Scott & White for mCRC were included if they received at least one cycle of modified FOLFOX6 with or without bevicizumab as first line therapy. Patients that received a leucovorin dose other than 20mg/m2 or 400mg/m2on their first cycle were excluded. Patient characteristics included demographics, site(s) of metastasis at initial diagnosis, and treatment history including chemotherapy and surgery. Primary outcome was date of death or last contact. Univariate and multivariate Cox proportional hazards regression analyses and Kaplan-Meier survival curves compared the effect of leucovorin dose on overall survival. Results: Of the 129 mCRC patients who received first line modified FOLFOX6, leucovorin 400 mg/m2 was administered to 71 (55%) patients and leucovorin 20mg/m2 to 58 (45%) patients. There were no differences between the groups except age at diagnosis, 61 vs. 66 years for high and low dose, respectively (p=0.02). In both univariate and multivariate Cox proportional hazards regression, lack of metastasis to the omentum at diagnosis (P=0.02) and resection or ablation at site of metastasis (P=0.003) were associated with better overall survival. Median survival time was 23 months for high dose group and 20 months for low dose group. There was no statistically significant difference in overall survival between the two groups (HR 1.020, 95%CI 0.677-1.536). Conclusions: In this single center retrospective study there was no difference in overall survival for mCRC patients treated with low (20mg/m2) vs. standard high dose (400mg/m2) leucovorin in first line FOLFOX. Limitations include the retrospective nature of the study and small sample size.