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A single-arm phase II trial of combined chemotherapy with S-1, oral leucovorin, and bevacizumab in heavily pre-treated patients with metastatic colorectal cancer

BACKGROUND: The mean 5–6-month survival after failed standard chemotherapy for metastatic colorectal cancer (mCRC) necessitates more effective treatments for refractory mCRC. For untreated mCRC, S-1 + oral leucovorin (SL) therapy offers promising results without severe toxicity. The ML18147 trial de...

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Autores principales: Yamaguchi, Kazuhisa, Taniguchi, Hiroya, Komori, Azusa, Narita, Yukiya, Nitta, Sohei, Nomura, Motoo, Kadowaki, Shigenori, Takahari, Daisuke, Ura, Takashi, Andoh, Masashi, Muro, Kei, Mori, Keita, Igarashi, Yoshinori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550068/
https://www.ncbi.nlm.nih.gov/pubmed/26311588
http://dx.doi.org/10.1186/s12885-015-1606-1
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author Yamaguchi, Kazuhisa
Taniguchi, Hiroya
Komori, Azusa
Narita, Yukiya
Nitta, Sohei
Nomura, Motoo
Kadowaki, Shigenori
Takahari, Daisuke
Ura, Takashi
Andoh, Masashi
Muro, Kei
Mori, Keita
Igarashi, Yoshinori
author_facet Yamaguchi, Kazuhisa
Taniguchi, Hiroya
Komori, Azusa
Narita, Yukiya
Nitta, Sohei
Nomura, Motoo
Kadowaki, Shigenori
Takahari, Daisuke
Ura, Takashi
Andoh, Masashi
Muro, Kei
Mori, Keita
Igarashi, Yoshinori
author_sort Yamaguchi, Kazuhisa
collection PubMed
description BACKGROUND: The mean 5–6-month survival after failed standard chemotherapy for metastatic colorectal cancer (mCRC) necessitates more effective treatments for refractory mCRC. For untreated mCRC, S-1 + oral leucovorin (SL) therapy offers promising results without severe toxicity. The ML18147 trial demonstrated that bevacizumab (Bev) prolongs overall survival after mCRC progression. We conducted a single-centre phase-II trial to evaluate the safety and efficacy of SL/Bev combination chemotherapy as mCRC salvage therapy. METHODS: Major eligibility criteria were confirmed adenocarcinoma diagnosis; age >20 years; Eastern Cooperative Oncology Group performance status, 0–2; and progression after administration/intolerance of/to approved drugs for mCRC. (5-FU, oxaliplatin, irinotecan, Bev, and anti-EGFR antibody, if KRAS wild-type). S-1 (80–120 mg/body) and leucovorin (25 mg) were orally administered in a 1-week-on/1-week-off schedule. Bev (5 mg/kg) was administered on day 1 of every 2-week cycle. The primary endpoint was disease control rate (DCR). RESULTS: A total of 31 patients were enrolled. DCR was 65 % [95 % confidence interval (CI), 48–100 %] and the response rate was 7 % (95 % CI, 0.7–22 %). One patient showing partial response to SL/Bev had a BRAF-mutant tumor. Median progression-free survival and overall survivals were 5.3 [95 % CI, 2.1–9.3] and 9.9 [95 % CI, 7.4–NA] months, respectively. The most-frequent grade-3/4 adverse events were mucositis (26 %) and diarrhea (11 %), which were manageable by dose reduction/interruption. CONCLUSIONS: SL/Bev showed impressive activity in refractory mCRC and was tolerable, suggesting its potential as an alternative chemotherapy for refractory mCRC. TRIAL REGISTRATION: This study has been registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry (IDUMIN000009083) on 11 October 2012. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1606-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-45500682015-08-27 A single-arm phase II trial of combined chemotherapy with S-1, oral leucovorin, and bevacizumab in heavily pre-treated patients with metastatic colorectal cancer Yamaguchi, Kazuhisa Taniguchi, Hiroya Komori, Azusa Narita, Yukiya Nitta, Sohei Nomura, Motoo Kadowaki, Shigenori Takahari, Daisuke Ura, Takashi Andoh, Masashi Muro, Kei Mori, Keita Igarashi, Yoshinori BMC Cancer Research Article BACKGROUND: The mean 5–6-month survival after failed standard chemotherapy for metastatic colorectal cancer (mCRC) necessitates more effective treatments for refractory mCRC. For untreated mCRC, S-1 + oral leucovorin (SL) therapy offers promising results without severe toxicity. The ML18147 trial demonstrated that bevacizumab (Bev) prolongs overall survival after mCRC progression. We conducted a single-centre phase-II trial to evaluate the safety and efficacy of SL/Bev combination chemotherapy as mCRC salvage therapy. METHODS: Major eligibility criteria were confirmed adenocarcinoma diagnosis; age >20 years; Eastern Cooperative Oncology Group performance status, 0–2; and progression after administration/intolerance of/to approved drugs for mCRC. (5-FU, oxaliplatin, irinotecan, Bev, and anti-EGFR antibody, if KRAS wild-type). S-1 (80–120 mg/body) and leucovorin (25 mg) were orally administered in a 1-week-on/1-week-off schedule. Bev (5 mg/kg) was administered on day 1 of every 2-week cycle. The primary endpoint was disease control rate (DCR). RESULTS: A total of 31 patients were enrolled. DCR was 65 % [95 % confidence interval (CI), 48–100 %] and the response rate was 7 % (95 % CI, 0.7–22 %). One patient showing partial response to SL/Bev had a BRAF-mutant tumor. Median progression-free survival and overall survivals were 5.3 [95 % CI, 2.1–9.3] and 9.9 [95 % CI, 7.4–NA] months, respectively. The most-frequent grade-3/4 adverse events were mucositis (26 %) and diarrhea (11 %), which were manageable by dose reduction/interruption. CONCLUSIONS: SL/Bev showed impressive activity in refractory mCRC and was tolerable, suggesting its potential as an alternative chemotherapy for refractory mCRC. TRIAL REGISTRATION: This study has been registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry (IDUMIN000009083) on 11 October 2012. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1606-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-08-27 /pmc/articles/PMC4550068/ /pubmed/26311588 http://dx.doi.org/10.1186/s12885-015-1606-1 Text en © Yamaguchi et al. 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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Yamaguchi, Kazuhisa
Taniguchi, Hiroya
Komori, Azusa
Narita, Yukiya
Nitta, Sohei
Nomura, Motoo
Kadowaki, Shigenori
Takahari, Daisuke
Ura, Takashi
Andoh, Masashi
Muro, Kei
Mori, Keita
Igarashi, Yoshinori
A single-arm phase II trial of combined chemotherapy with S-1, oral leucovorin, and bevacizumab in heavily pre-treated patients with metastatic colorectal cancer
title A single-arm phase II trial of combined chemotherapy with S-1, oral leucovorin, and bevacizumab in heavily pre-treated patients with metastatic colorectal cancer
title_full A single-arm phase II trial of combined chemotherapy with S-1, oral leucovorin, and bevacizumab in heavily pre-treated patients with metastatic colorectal cancer
title_fullStr A single-arm phase II trial of combined chemotherapy with S-1, oral leucovorin, and bevacizumab in heavily pre-treated patients with metastatic colorectal cancer
title_full_unstemmed A single-arm phase II trial of combined chemotherapy with S-1, oral leucovorin, and bevacizumab in heavily pre-treated patients with metastatic colorectal cancer
title_short A single-arm phase II trial of combined chemotherapy with S-1, oral leucovorin, and bevacizumab in heavily pre-treated patients with metastatic colorectal cancer
title_sort single-arm phase ii trial of combined chemotherapy with s-1, oral leucovorin, and bevacizumab in heavily pre-treated patients with metastatic colorectal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550068/
https://www.ncbi.nlm.nih.gov/pubmed/26311588
http://dx.doi.org/10.1186/s12885-015-1606-1
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