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A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients

PURPOSE: Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal c...

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Autores principales: Kim, Youjin, Kim, Tae Won, Han, Sae Won, Ahn, Joong Bae, Kim, Seung Tae, Lee, Jeeyun, Park, Joon Oh, Park, Young Suk, Lim, Ho Yeong, Kang, Won Ki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Cancer Association 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639242/
https://www.ncbi.nlm.nih.gov/pubmed/30477287
http://dx.doi.org/10.4143/crt.2018.379
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author Kim, Youjin
Kim, Tae Won
Han, Sae Won
Ahn, Joong Bae
Kim, Seung Tae
Lee, Jeeyun
Park, Joon Oh
Park, Young Suk
Lim, Ho Yeong
Kang, Won Ki
author_facet Kim, Youjin
Kim, Tae Won
Han, Sae Won
Ahn, Joong Bae
Kim, Seung Tae
Lee, Jeeyun
Park, Joon Oh
Park, Young Suk
Lim, Ho Yeong
Kang, Won Ki
author_sort Kim, Youjin
collection PubMed
description PURPOSE: Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC). MATERIALS AND METHODS: Patients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m(2) plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m(2) twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity. RESULTS: From January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation. CONCLUSION: Based on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity.
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spelling pubmed-66392422019-07-26 A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients Kim, Youjin Kim, Tae Won Han, Sae Won Ahn, Joong Bae Kim, Seung Tae Lee, Jeeyun Park, Joon Oh Park, Young Suk Lim, Ho Yeong Kang, Won Ki Cancer Res Treat Original Article PURPOSE: Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC). MATERIALS AND METHODS: Patients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m(2) plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m(2) twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity. RESULTS: From January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation. CONCLUSION: Based on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity. Korean Cancer Association 2019-07 2018-11-21 /pmc/articles/PMC6639242/ /pubmed/30477287 http://dx.doi.org/10.4143/crt.2018.379 Text en Copyright © 2019 by the Korean Cancer Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Kim, Youjin
Kim, Tae Won
Han, Sae Won
Ahn, Joong Bae
Kim, Seung Tae
Lee, Jeeyun
Park, Joon Oh
Park, Young Suk
Lim, Ho Yeong
Kang, Won Ki
A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients
title A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients
title_full A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients
title_fullStr A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients
title_full_unstemmed A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients
title_short A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients
title_sort single arm, phase ii study of simvastatin plus xelox and bevacizumab as first-line chemotherapy in metastatic colorectal cancer patients
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639242/
https://www.ncbi.nlm.nih.gov/pubmed/30477287
http://dx.doi.org/10.4143/crt.2018.379
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