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Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer

A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gas...

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Autores principales: Inokuchi, M, Yamashita, T, Yamada, H, Kojima, K, Ichikawa, W, Nihei, Z, Kawano, T, Sugihara, K
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361252/
https://www.ncbi.nlm.nih.gov/pubmed/16570038
http://dx.doi.org/10.1038/sj.bjc.6603072
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author Inokuchi, M
Yamashita, T
Yamada, H
Kojima, K
Ichikawa, W
Nihei, Z
Kawano, T
Sugihara, K
author_facet Inokuchi, M
Yamashita, T
Yamada, H
Kojima, K
Ichikawa, W
Nihei, Z
Kawano, T
Sugihara, K
author_sort Inokuchi, M
collection PubMed
description A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was administered orally at 80 mg m(−2) day(−1) from day 1 to 14 of a 28-day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of 70 mg m(−2) day(−1), stepping up to 100 mg m(−2). The treatment was repeated every 4 weeks, unless disease progression was observed. In the phase I portion, the MTD of CPT-11 was presumed to be 100 mg m(−2), because 66.6% of patients (two of three) developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m(−2)) experienced grade 4 haematological or grade 3 nonhaematological toxicities at second course, followed by the dose reduction of CPT-11 from the third course. Considering safety and the ability to continue treatment, the final RD was determined to be 80 mg m(−2). In the phase II portion, 42 patients including seven patients in the final RD phase I portion were evaluated. The median treatment course was five (range: 1–13). The incidences of severe (grade 3–4) haematological and nonhaematological toxicities were 19 and 10%, respectively, but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2–76.6%), and the median survival time was 444 days. Our phase I/II trial showed S-1 combined with CPT-11 is effective for AGC and is well tolerated, with acceptable toxicity.
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spelling pubmed-23612522009-09-10 Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer Inokuchi, M Yamashita, T Yamada, H Kojima, K Ichikawa, W Nihei, Z Kawano, T Sugihara, K Br J Cancer Clinical Study A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was administered orally at 80 mg m(−2) day(−1) from day 1 to 14 of a 28-day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of 70 mg m(−2) day(−1), stepping up to 100 mg m(−2). The treatment was repeated every 4 weeks, unless disease progression was observed. In the phase I portion, the MTD of CPT-11 was presumed to be 100 mg m(−2), because 66.6% of patients (two of three) developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m(−2)) experienced grade 4 haematological or grade 3 nonhaematological toxicities at second course, followed by the dose reduction of CPT-11 from the third course. Considering safety and the ability to continue treatment, the final RD was determined to be 80 mg m(−2). In the phase II portion, 42 patients including seven patients in the final RD phase I portion were evaluated. The median treatment course was five (range: 1–13). The incidences of severe (grade 3–4) haematological and nonhaematological toxicities were 19 and 10%, respectively, but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2–76.6%), and the median survival time was 444 days. Our phase I/II trial showed S-1 combined with CPT-11 is effective for AGC and is well tolerated, with acceptable toxicity. Nature Publishing Group 2006-04-24 2006-03-28 /pmc/articles/PMC2361252/ /pubmed/16570038 http://dx.doi.org/10.1038/sj.bjc.6603072 Text en Copyright © 2006 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Clinical Study
Inokuchi, M
Yamashita, T
Yamada, H
Kojima, K
Ichikawa, W
Nihei, Z
Kawano, T
Sugihara, K
Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer
title Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer
title_full Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer
title_fullStr Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer
title_full_unstemmed Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer
title_short Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer
title_sort phase i/ii study of s-1 combined with irinotecan for metastatic advanced gastric cancer
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361252/
https://www.ncbi.nlm.nih.gov/pubmed/16570038
http://dx.doi.org/10.1038/sj.bjc.6603072
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