Relationship between UGT1A1*27 and UGT1A1*7 polymorphisms and irinotecan‐related toxicities in patients with lung cancer

BACKGROUND: The objective of this study was to evaluate the effects of gene polymorphisms, including UGT1A1*7, *27, and *29, on the safety of irinotecan therapy. METHODS: The eligibility criteria were: lung cancer patients scheduled to undergo irinotecan therapy, aged ≥ 20 years, with a performance status of 0–2. Thirty‐one patients were enrolled and their blood was collected and used to examine the frequency of UGT1A1*6, *7, *27, *28, and *29 polymorphisms and the concentrations of irinotecan, SN‐38, and SN‐38G after irinotecan therapy. RESULTS: The patients’ characteristics were as follows: male/female 25/6, median age 71 years (range 55–84), stage IIB/IIIA/IIIB/IV 2/6/11/12, and adenocarcinoma/squamous cell carcinoma/small cell carcinoma/other 14/10/3/4, respectively. The −/−, *6/−, *7/−, *27/−, *28/−, and *29/− UGT1A1 gene polymorphisms were observed in 10 (32%), 10 (32%), 2 (6%), 2 (6%), 7 (23%), and 0 (0%) cases, respectively. The UGT1A1*27 polymorphism occurred separately from the UGT1A1*28 polymorphism. The lowest leukocyte counts of the patients with the UGT1A1*27 and UGT1A1*6 gene polymorphisms were lower than those observed in the wild‐type patients. SN‐38 tended to remain in the blood for a prolonged period after the infusion of irinotecan in patients with UGT1A1*27 or UGT1A1*28 polymorphisms. No severe myelotoxicity was seen in the patients with UGT1A1*7. CONCLUSION: UGT1A1*27 can occur separately from UGT1A1*28 and is related to leukopenia during irinotecan treatment. UGT1A1*7 is less relevant to irinotecan‐induced toxicities, and UGT1A1*29 seems to have little clinical impact.