Evaluation of the Expression Profile of Irinotecan-Induced Diarrhea in Patients with Colorectal Cancer

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 14; no. 4; p. 377
• Main Authors: Okunaka, Mashiro, Kano, Daisuke, Matsui, Reiko, Kawasaki, Toshikatsu, Uesawa, Yoshihiro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.04.2021; MDPI
• Subjects: Cancer therapies; Chemotherapy; Colorectal cancer; Dehydrogenases; Diarrhea; Drug interactions; fluorouracil; irinotecan; Patients; Pharmaceutical industry; Potassium; S-1; spontaneous reporting system; Japan; spontaneous reporting system; irinotecan; time-to-onset analysis; Japanese Adverse Drug Event Report (JADER); S-1; fluorouracil; Weibull distribution; pharmacovigilance; chemotherapy; diarrhea
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph14040377

Irinotecan (CPT-11) is widely used for the treatment of unresectable colorectal cancer in combination with fluoropyrimidines, such as 5-fluorouracil and S-1. Diarrhea is one of the adverse effects associated with CPT-11 and frequently reported by patients treated with CPT-11-containing regimens combined with oral fluoropyrimidines. However, the mechanisms involved in this process, as well as whether fluctuations in the frequency and differences in the onset time of diarrhea with each CPT-11-containing regimen are caused by drug interactions remain unclear. Therefore, we examined the incidence of diarrhea caused by each CPT-11-containing regimen in patients with colorectal cancer using data from the large voluntary reporting Japanese Adverse Drug Event Report (JADER) database. Firstly, we searched for suspected drugs related to the occurrence of diarrhea using reported odds ratio and calculated the signal score to assess drug-drug interactions. Subsequently, we conducted a time-to-onset analysis using Weibull distribution. The results showed that the combination of CPT-11 with S-1 increased the frequency of diarrhea due to a pharmacological interaction but delayed its onset. The present results may contribute to the appropriate management of drug-induced adverse effects by healthcare professionals.