Clarithromycin co-administration does not increase irinotecan (CPT-11) toxicity in colorectal cancer patients

Irinotecan (CPT-11) is used to treat advanced colorectal cancer. The drug is activated by carboxylesterases and rendered inactive by CYP3A4. Recently, the efficacy of combining CPT-11 and anti-epidermal growth factor receptor (EGFR) agents was confirmed in patients with KRAS wild-type metastatic colorectal cancer. Clarithromycin (CAM) is a strong CYP3A inhibitor often used to prevent rash associated with anti-EGFR therapy. The objective of this study was to evaluate the risk of increased neutropenia and diarrhea in combining CPT-11 and CAM. Retrospective analyses were conducted at Osaka National Hospital (Osaka, Japan) on the records of colorectal cancer patients treated with a CPT-11-containing regimen between November 2006 and January 2014. The incidence of neutropenia and diarrhea was compared between patients who received CPT-11 and CAM and patients who received CPT-11 without CAM. One-hundred and twenty-eight patients were included in this study, of whom 21 were concomitantly treated with CAM and 107 were not. There was no difference in the incidence of grade 3-4 neutropenia between the CAM co-administration group (10%) and the non-CAM group (16%) [Odds ratio: 0.56 (95% confidence interval: 0.12-2.62), p = 0.45]. No difference in the incidence of grade 3-4 diarrhea was found between the CAM co-administration group (0%) and the non-CAM group (4%) (p = 0.37). This study did not identify an increase in CPT-11 toxicity by co-administration with CAM.