Cargando…
Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours
BACKGROUND: TAS-102 consists of α, α, α-trifluorothymidine (TFT) and an inhibitor of thymidine phosphorylase (TPI). We conducted a dose-escalation phase I study in Japanese patients with advanced solid tumours. METHODS: TAS-102 was administered twice daily on days 1–5 and days 8–12 in a 28-day cycle...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405214/ https://www.ncbi.nlm.nih.gov/pubmed/22735906 http://dx.doi.org/10.1038/bjc.2012.274 |
_version_ | 1782239098519420928 |
---|---|
author | Doi, T Ohtsu, A Yoshino, T Boku, N Onozawa, Y Fukutomi, A Hironaka, S Koizumi, W Sasaki, T |
author_facet | Doi, T Ohtsu, A Yoshino, T Boku, N Onozawa, Y Fukutomi, A Hironaka, S Koizumi, W Sasaki, T |
author_sort | Doi, T |
collection | PubMed |
description | BACKGROUND: TAS-102 consists of α, α, α-trifluorothymidine (TFT) and an inhibitor of thymidine phosphorylase (TPI). We conducted a dose-escalation phase I study in Japanese patients with advanced solid tumours. METHODS: TAS-102 was administered twice daily on days 1–5 and days 8–12 in a 28-day cycle to patients with solid tumours refractory to standard chemotherapy, to determine its maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetics (PKs). MTD was evaluated in cycle 1. RESULTS: Safety and PKs were evaluated in 21 patients treated with TAS-102 at 30, 40, 50, 60, or 70 mg m(−2) per day. DLTs, such as grade 4 leucopenia, grade 4 neutropenia, and grade 4 thrombocytopenia, were observed in two patients at doses of 30 and 70 mg m(−2). α, α, α-trifluorothymidine and TPI exposures increased dose dependently, and the percentage of decrease in neutrophil count and TFT exposure were significantly correlated. The disease control rate was 50.0% with a median progression-free survival of 2.4 months in 18 colorectal cancer patients. The dose of TAS-102 was not increased above 70 mg m(−2) per day because of the increased tendency for grade 3 and 4 neutropenia, and 70 mg m(−2) per day was the recommended dose for phase II studies. CONCLUSIONS: TAS-102 at 70 mg m(−2) per day was tolerated in Japanese patients with advanced solid tumours. Phase II studies are ongoing in patients with colorectal cancer. |
format | Online Article Text |
id | pubmed-3405214 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-34052142013-07-24 Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours Doi, T Ohtsu, A Yoshino, T Boku, N Onozawa, Y Fukutomi, A Hironaka, S Koizumi, W Sasaki, T Br J Cancer Clinical Study BACKGROUND: TAS-102 consists of α, α, α-trifluorothymidine (TFT) and an inhibitor of thymidine phosphorylase (TPI). We conducted a dose-escalation phase I study in Japanese patients with advanced solid tumours. METHODS: TAS-102 was administered twice daily on days 1–5 and days 8–12 in a 28-day cycle to patients with solid tumours refractory to standard chemotherapy, to determine its maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetics (PKs). MTD was evaluated in cycle 1. RESULTS: Safety and PKs were evaluated in 21 patients treated with TAS-102 at 30, 40, 50, 60, or 70 mg m(−2) per day. DLTs, such as grade 4 leucopenia, grade 4 neutropenia, and grade 4 thrombocytopenia, were observed in two patients at doses of 30 and 70 mg m(−2). α, α, α-trifluorothymidine and TPI exposures increased dose dependently, and the percentage of decrease in neutrophil count and TFT exposure were significantly correlated. The disease control rate was 50.0% with a median progression-free survival of 2.4 months in 18 colorectal cancer patients. The dose of TAS-102 was not increased above 70 mg m(−2) per day because of the increased tendency for grade 3 and 4 neutropenia, and 70 mg m(−2) per day was the recommended dose for phase II studies. CONCLUSIONS: TAS-102 at 70 mg m(−2) per day was tolerated in Japanese patients with advanced solid tumours. Phase II studies are ongoing in patients with colorectal cancer. Nature Publishing Group 2012-07-24 2012-06-26 /pmc/articles/PMC3405214/ /pubmed/22735906 http://dx.doi.org/10.1038/bjc.2012.274 Text en Copyright © 2012 Cancer Research UK https://creativecommons.org/licenses/by-nc-sa/3.0/From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Clinical Study Doi, T Ohtsu, A Yoshino, T Boku, N Onozawa, Y Fukutomi, A Hironaka, S Koizumi, W Sasaki, T Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours |
title | Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours |
title_full | Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours |
title_fullStr | Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours |
title_full_unstemmed | Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours |
title_short | Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours |
title_sort | phase i study of tas-102 treatment in japanese patients with advanced solid tumours |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405214/ https://www.ncbi.nlm.nih.gov/pubmed/22735906 http://dx.doi.org/10.1038/bjc.2012.274 |
work_keys_str_mv | AT doit phaseistudyoftas102treatmentinjapanesepatientswithadvancedsolidtumours AT ohtsua phaseistudyoftas102treatmentinjapanesepatientswithadvancedsolidtumours AT yoshinot phaseistudyoftas102treatmentinjapanesepatientswithadvancedsolidtumours AT bokun phaseistudyoftas102treatmentinjapanesepatientswithadvancedsolidtumours AT onozaway phaseistudyoftas102treatmentinjapanesepatientswithadvancedsolidtumours AT fukutomia phaseistudyoftas102treatmentinjapanesepatientswithadvancedsolidtumours AT hironakas phaseistudyoftas102treatmentinjapanesepatientswithadvancedsolidtumours AT koizumiw phaseistudyoftas102treatmentinjapanesepatientswithadvancedsolidtumours AT sasakit phaseistudyoftas102treatmentinjapanesepatientswithadvancedsolidtumours |