P-178 - Frequency report of irinotecan toxicity in Iranian population: Is genomic differences responsible?

Abstract

Introduction: Irinotecan is a drug of choice as monotherapy or in combination for treatment of some cancers including colorectal, esophageal/gastric and etc. Its use is limited by severe toxicities such as neutropenia and diarrhea. These adverse effects negatively impact therapeutic outcomes and delay subsequent cycles of chemotherapy resulting in dose reductions and treatment discontinuation. Genotyping of UGT1A1 may help predicting serious toxicities of irinotecan in more sensitive patients and modify the starting dose. Incidences of toxicities and frequency of different genotypes of UGT1A1 differs among worldwide ethnicities. We aimed to assess the prevalence of irinotecan induced neutropenia and diarrhea during past one year in one of referral hematology-oncology center in Iran. We also reviewed the related data of irinotecan toxicity and its relation to UGT 1A1 enzyme polymorphisms. Methods: We prospectively collected all data over the prevalence of irinotecan induced neutropenia and diarrhea for last one year in all cancer patients who received irinotecan by standard doses in our hospital. We also performed a literature search according to frequencies of irinotecan toxicities and UGT 1A1 enzyme polymorphisms. Materials were obtained by searching ELSEVIER, web of knowledge, PubMed, Scopus, clinical trials, and Cochrane database of systematic reviews in different clinical studies which enrolled patients with different ethnicities and implemented diverse regimens containing irinotecan. Results: From 150 case of irinotecan administration, less than 5% have been affected by irinotecan adverse effects. The prevalence of diarrhea associated by irinotecan administration is lower in Iranian patients than worldwide reports. As reported by other paper, Iranian population has a heterozygous for UGT1A1 polymorphisms and we think that this association can explain these differences in Iranian cancer patients. On the other hand, literature review indicated that, there is a reliable relationship between irinotecan toxicities and UGT1A1 polymorphisms based on diverse trials have been published until now. Conclusion: Our results confirmed the possible association of irinotecan induced adverse effects and UGT 1A1 enzyme polymorphisms. Frequency of these adverse effects varies substantially in different setting. Hence, clinicians should keep in mind these differences and accommodate patients' treatment plan based on local toxicity reports. Surly, ethnicity is a matter of interest for irinotecan associated adverse effects.