Risk factors for irinotecan-induced hepatotoxicity: a retrospective cohort study

Irinotecan is a potent chemotherapeutic agent used as a neoadjuvant in colorectal cancer liver metastasis and significantly enhances five-year survival rates. Recently, irinotecan-associated hepatotoxicity was a significant concern. Given the limited study in this area, we aimed to identify risk factors associated with irinotecan-induced hepatotoxicity.

This is a retrospective cohort study at King Saud University Medical City in Riyadh. The study encompassed all adult cancer patients who received irinotecan treatment between Jun 2017 and December 2023. The clinical records of patients were reviewed to assess factors associated with hepatotoxicity. Time-to-event analyses were performed using time-varying exposure.

The study includes 229 adult cancer patients who received irinotecan-based treatment. Median age was 58 years, and colorectal cancer was the most diagnosed type of cancer (68.6%). Over a median follow-up of 103 days, the incidence of hepatotoxicity was 19.2% (n=44). In the adjusted analysis, higher baseline AST was associated with an increased hazard of hepatotoxicity (HR = 1.01; 95% CI: 1.01-1.02; p = 0.001). Cumulative irinotecan dose showed an inverse association with hepatotoxicity, with lower hazards observed in the medium cumulative dose group (HR = 0.36, 95% CI: 0.14-0.91, p = 0.031) and high cumulative dose group (HR = 0.06, 95% CI: 0.01-0.48, p = 0.008) compared with the low cumulative dose group.

In summary, an inverse association was observed between cumulative irinotecan dose and hepatotoxicity. A higher baseline AST was also associated with hepatotoxicity, warranting careful assessment of pretreatment liver enzymes and closer monitoring during the early treatment period. Further studies are needed to validate these findings and investigate additional predictors of irinotecan-related hepatotoxicity.