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Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial

BACKGROUND: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded,...

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Autores principales: Xu, Rui-Hua, Shen, Lin, Wang, Ke-Ming, Wu, Gang, Shi, Chun-Mei, Ding, Ke-Feng, Lin, Li-Zhu, Wang, Jin-Wan, Xiong, Jian-Ping, Wu, Chang-Ping, Li, Jin, Liu, Yun-Peng, Wang, Dong, Ba, Yi, Feng, Jue-Ping, Bai, Yu-Xian, Bi, Jing-Wang, Ma, Li-Wen, Lei, Jian, Yang, Qing, Yu, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741870/
https://www.ncbi.nlm.nih.gov/pubmed/29273089
http://dx.doi.org/10.1186/s40880-017-0263-y
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author Xu, Rui-Hua
Shen, Lin
Wang, Ke-Ming
Wu, Gang
Shi, Chun-Mei
Ding, Ke-Feng
Lin, Li-Zhu
Wang, Jin-Wan
Xiong, Jian-Ping
Wu, Chang-Ping
Li, Jin
Liu, Yun-Peng
Wang, Dong
Ba, Yi
Feng, Jue-Ping
Bai, Yu-Xian
Bi, Jing-Wang
Ma, Li-Wen
Lei, Jian
Yang, Qing
Yu, Hao
author_facet Xu, Rui-Hua
Shen, Lin
Wang, Ke-Ming
Wu, Gang
Shi, Chun-Mei
Ding, Ke-Feng
Lin, Li-Zhu
Wang, Jin-Wan
Xiong, Jian-Ping
Wu, Chang-Ping
Li, Jin
Liu, Yun-Peng
Wang, Dong
Ba, Yi
Feng, Jue-Ping
Bai, Yu-Xian
Bi, Jing-Wang
Ma, Li-Wen
Lei, Jian
Yang, Qing
Yu, Hao
author_sort Xu, Rui-Hua
collection PubMed
description BACKGROUND: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. METHODS: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. RESULTS: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41–0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3–4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). CONCLUSION: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium
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spelling pubmed-57418702018-01-03 Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial Xu, Rui-Hua Shen, Lin Wang, Ke-Ming Wu, Gang Shi, Chun-Mei Ding, Ke-Feng Lin, Li-Zhu Wang, Jin-Wan Xiong, Jian-Ping Wu, Chang-Ping Li, Jin Liu, Yun-Peng Wang, Dong Ba, Yi Feng, Jue-Ping Bai, Yu-Xian Bi, Jing-Wang Ma, Li-Wen Lei, Jian Yang, Qing Yu, Hao Chin J Cancer Original Article BACKGROUND: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. METHODS: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. RESULTS: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41–0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3–4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). CONCLUSION: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium BioMed Central 2017-12-22 /pmc/articles/PMC5741870/ /pubmed/29273089 http://dx.doi.org/10.1186/s40880-017-0263-y Text en © The Author(s) 2017 Open AccessThis 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 Original Article
Xu, Rui-Hua
Shen, Lin
Wang, Ke-Ming
Wu, Gang
Shi, Chun-Mei
Ding, Ke-Feng
Lin, Li-Zhu
Wang, Jin-Wan
Xiong, Jian-Ping
Wu, Chang-Ping
Li, Jin
Liu, Yun-Peng
Wang, Dong
Ba, Yi
Feng, Jue-Ping
Bai, Yu-Xian
Bi, Jing-Wang
Ma, Li-Wen
Lei, Jian
Yang, Qing
Yu, Hao
Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial
title Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial
title_full Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial
title_fullStr Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial
title_full_unstemmed Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial
title_short Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial
title_sort famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase ii clinical trial
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741870/
https://www.ncbi.nlm.nih.gov/pubmed/29273089
http://dx.doi.org/10.1186/s40880-017-0263-y
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