Chie Mikami

Short-term results of laparoscopic surgery after preoperative chemoradiation for clinically staged T3 and T4 rectal cancer

The feasibility of laparoscopic surgery for clinically staged T3 and T4 rectal cancer has not been clearly defined specifically in cases following preoperative chemoradiation therapy (CRT). Our aim was to investigate the feasibility of laparoscopic surgery after preoperative CRT for clinically staged T3 and T4 rectal cancer.

A multicenter exploratory study of irinotecan-based chemotherapy on UGT1A1 polymorphisms for patients with colorectal cancer.

563 Background: Recent pharmacogenetic studies have revealed a significant association between uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms *28 and *6 and toxicities such as severe diarrhea and neutropenia under treatment with irinotecan. Moreover, the latter of these two polymorphisms is specifically detected in East Asian populations. We performed a prospective study to determine the optimal dose of this drug depending on which polymorphism is present in order to maximize the effectiveness of therapy while avoiding side effects. Methods: 59 patients from 11 institutions were enrolled in this study. Patients were assigned to one of the following three groups: wild type (*1/*1), heterozygous (*28/*1, *6/*1), or homozygous (*28/*28, *6/*6*, *28/*6*). The double heterozygous state (*28/*6) was included within the homozygous group. Second-line FOLFIRI was administered, with the dose of irinotecan at 150 mg/m2, in the wild type and heterozygous groups and at 100 mg/m2 in the homozygo...

The role of UGT1A1 polymorphisms (*28 and *6) in Japanese cancer patients.

570 Background: Combination protocol using FU-LV with irinotecan (FOLFIRI) is currently regarded as standard first-line therapy in advanced colorectal cancer (CRC). Although irinotecan prolongs survival, it causes severe diarrhea and neutropenia. Recent pharmacogenetic studies on irinotecan have revealed significant associations of UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms *28 and *6, the latter being specifically detected in East Asians resulting in severe toxicity. It is necessary that the dose-finding trial that decided the optimal dose according to the gene polymorphism to draw out the maximum therapeutic effect while evading the side effect. Here we present the result of prospective trial of the safety about FOLFIRI therapy according to each gene type of UGT1A1 for Japanese patients with advanced CRC. METHODS From 2008, 250 Japanese patients in TOKUSHIMA University were enrolled in this study. Homo group (*6/*6 and *28/*28 or a both hetero types), hetero group (It was *28 and either *6 was hetero type), and wild group (*28 and *6 were wild types) were defined. On the 23 patients with advanced CRC treated with FOLFIRI after standard chemotherapy, wild and homo groups were administered 150mg/m2 irinotecan, and homo group was 100mg/m2. RESULTS On the 23 patients, the genotypes of UGT1A1 *28 were homozygous in 1 (0.5%) and heterozygous in 5 (28%), *6 were homozygous in 0 and heterozygous in 6 (26%). In *6 heterozygous patients, severe toxicities (grade 3 or more) were found (33%), but in *28 heterozygous patients were not (0%). There was no decrease of irinotecan doses in each group. In Japanese people, UGT1A1 *6 polymorphisms were higher than *28 (*6 homo 3%, hetero 27% vs *28 homo 0.5%, hetero 13%). CONCLUSIONS When the dosage of irinotecan is decided, it is necessary to consider the UGT1A1 *6 heterozygous in Japanese cancer patients. [Table: see text].