Abstract
e14572 Background: 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 such as severe diarrhea and neutropenia. 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 final report of prospective trial of safety and efficacy about FOLFIRI ± bevacizumab (Bev) therapy according to each gene type of UGT1A1for Japanese patients with advanced CRC in second-line setting. Methods: Between September 2008 and March 2012, 59 patients were enrolled in this study. Grouping was defined as follows: wild group; both *28 and *6 were wild types, hetero group; *28 and either *6 was hetero type, and homo group; 28/*28 and *6/*6* or a both hetero types. In the 59 patients with advanced CRC treated with FOLFIRI ± Bev as a second line, wild and hetero groups were administered 150mg/m2 irinotecan, and homo group was 100mg/m2. The incidences of severe toxicities according to gene type of UGT1A1, the response rate and progression-free survival were investigated. Results: In the 59 patients, wild group was 28 (47%), hetero group was 26 (44.1%) and homo group was 5 (8.5%). 8 patients (29%) showed severe toxicities (grade 3 or more) in wild group, 5 patients (19%) in hetero group, 1 patient (20%) in homo group (P=0.71). Regarding the response rate, CR, PR, SD, PD was observed in 1 (4.0%), 1 (4.0%), 5 (20.0%) and 18 patients (72.0%), respectively in wild group, 0 (0.0%), 2 (8.3%), 5 (20.8%) and 17 patients (70.8%), in hetero group, 0 (0.0%), 0 (0.0%), 1 (20.0%) and 4 patients (80.0%), in homo group. The overall response rate (CR+PR) was 8.0% in wild group, 8.3% in hetero group, 0% in homo group (P=0.80). As for progression-free survival, the number of cycle to PD was 12.1 cycles (2-35 cycles) in wild group, 8.3 (2-20) in hetero group, 9.8 (6-14) in homo group (P=0.15). Conclusions: The dosages of 150mg/m2 irinotecan in hetero group, 100mg/m2 in homo group are safe and effective in FOLFIRI ± Bev therapy in the second line. Clinical trial information: UMIN000004773.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
