Phase I study of TAS-102 and irinotecan combination therapy in Japanese patients with advanced colorectal cancer

Background TAS-102 is a nucleoside antitumor agent consisting of trifluridine (FTD) and tipiracil hydrochloride (TPI). We investigated the recommended dose (RD) of TAS-102 plus irinotecan for metastatic colorectal cancer refractory to 5-fluorouracil (5-FU) and oxaliplatin. Methods This study was use...

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Main Authors:	Doi, Toshihiko, Yoshino, Takayuki, Fuse, Nozomu, Boku, Narikazu, Yamazaki, Kentaro, Koizumi, Wasaburo, Shimada, Ken, Takinishi, Yasutaka, Ohtsu, Atsushi
Format:	Online
Language:	English
Published:	Springer US 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768213/

id	pubmed-4768213
recordtype	oai_dc
spelling	pubmed-47682132016-03-29 Phase I study of TAS-102 and irinotecan combination therapy in Japanese patients with advanced colorectal cancer Doi, Toshihiko Yoshino, Takayuki Fuse, Nozomu Boku, Narikazu Yamazaki, Kentaro Koizumi, Wasaburo Shimada, Ken Takinishi, Yasutaka Ohtsu, Atsushi Phase I Studies Background TAS-102 is a nucleoside antitumor agent consisting of trifluridine (FTD) and tipiracil hydrochloride (TPI). We investigated the recommended dose (RD) of TAS-102 plus irinotecan for metastatic colorectal cancer refractory to 5-fluorouracil (5-FU) and oxaliplatin. Methods This study was used a escalated dose of TAS-102 (40–70 mg/m2/day, for 5 days a week with 2 days rest for 2 weeks, followed by a 14-day rest) with a fixed dose of irinotecan (150 mg/m2 on Days 1 and 15 of a 28-day schedule). The primary endpoints were determination of RD and assessment of safety. Results Ten patients were enrolled; 7 at the Level 1 (50 mg/m2/day) and 3 at the Level 2 (60 mg/m2/day). One patient at Level 1 was excluded from the analysis of dose-limiting toxicities (DLT) and efficacy. Five DLTs occurred in 3 patients; 1 patient at Level 1 (Grade 3 febrile neutropenia and Grade 4 neutropenia), and 2 patients at Level 2 (Grade 3 febrile neutropenia in two patients and Grade 4 neutropenia in one). Grade 3 or higher treatment-related adverse events were neutropenia (100 %), leukopenia (70 %), febrile neutropenia (30 %) and lymphopenia, anaemia (20 % each). 2 patients (22 %) achieved partial response with the duration of response were 112 and 799 days. Conclusion The RD was determined to be 50 mg/m2/day of TAS-102 combined with 150 mg/m2 of irinotecan although further investigation to explore optimal regimen is warranted. Springer US 2015-07-12 2015 /pmc/articles/PMC4768213/ /pubmed/26163340 http://dx.doi.org/10.1007/s10637-015-0271-1 Text en © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Doi, Toshihiko Yoshino, Takayuki Fuse, Nozomu Boku, Narikazu Yamazaki, Kentaro Koizumi, Wasaburo Shimada, Ken Takinishi, Yasutaka Ohtsu, Atsushi
spellingShingle	Doi, Toshihiko Yoshino, Takayuki Fuse, Nozomu Boku, Narikazu Yamazaki, Kentaro Koizumi, Wasaburo Shimada, Ken Takinishi, Yasutaka Ohtsu, Atsushi Phase I study of TAS-102 and irinotecan combination therapy in Japanese patients with advanced colorectal cancer
author_facet	Doi, Toshihiko Yoshino, Takayuki Fuse, Nozomu Boku, Narikazu Yamazaki, Kentaro Koizumi, Wasaburo Shimada, Ken Takinishi, Yasutaka Ohtsu, Atsushi
author_sort	Doi, Toshihiko
title	Phase I study of TAS-102 and irinotecan combination therapy in Japanese patients with advanced colorectal cancer
title_short	Phase I study of TAS-102 and irinotecan combination therapy in Japanese patients with advanced colorectal cancer
title_full	Phase I study of TAS-102 and irinotecan combination therapy in Japanese patients with advanced colorectal cancer
title_fullStr	Phase I study of TAS-102 and irinotecan combination therapy in Japanese patients with advanced colorectal cancer
title_full_unstemmed	Phase I study of TAS-102 and irinotecan combination therapy in Japanese patients with advanced colorectal cancer
title_sort	phase i study of tas-102 and irinotecan combination therapy in japanese patients with advanced colorectal cancer
description	Background TAS-102 is a nucleoside antitumor agent consisting of trifluridine (FTD) and tipiracil hydrochloride (TPI). We investigated the recommended dose (RD) of TAS-102 plus irinotecan for metastatic colorectal cancer refractory to 5-fluorouracil (5-FU) and oxaliplatin. Methods This study was used a escalated dose of TAS-102 (40–70 mg/m2/day, for 5 days a week with 2 days rest for 2 weeks, followed by a 14-day rest) with a fixed dose of irinotecan (150 mg/m2 on Days 1 and 15 of a 28-day schedule). The primary endpoints were determination of RD and assessment of safety. Results Ten patients were enrolled; 7 at the Level 1 (50 mg/m2/day) and 3 at the Level 2 (60 mg/m2/day). One patient at Level 1 was excluded from the analysis of dose-limiting toxicities (DLT) and efficacy. Five DLTs occurred in 3 patients; 1 patient at Level 1 (Grade 3 febrile neutropenia and Grade 4 neutropenia), and 2 patients at Level 2 (Grade 3 febrile neutropenia in two patients and Grade 4 neutropenia in one). Grade 3 or higher treatment-related adverse events were neutropenia (100 %), leukopenia (70 %), febrile neutropenia (30 %) and lymphopenia, anaemia (20 % each). 2 patients (22 %) achieved partial response with the duration of response were 112 and 799 days. Conclusion The RD was determined to be 50 mg/m2/day of TAS-102 combined with 150 mg/m2 of irinotecan although further investigation to explore optimal regimen is warranted.
publisher	Springer US
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768213/
_version_	1613543619486023680

Phase I study of TAS-102 and irinotecan combination therapy in Japanese patients with advanced colorectal cancer

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