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Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer

BACKGROUND: Extensive-disease small-cell lung cancer (ED-SCLC) is characterized by rapid progression and relapse, despite high initial response rates to chemotherapy. The primary objective of this trial was to demonstrate the non-inferiority of amrubicin and cisplatin (AP) combination therapy compar...

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Autores principales: Sun, Yan, Cheng, Ying, Hao, Xuezhi, Wang, Jie, Hu, Chengping, Han, Baohui, Liu, Xiaoqing, Zhang, Li, Wan, Huiping, Xia, Zhongjun, Liu, Yunpeng, Li, Wei, Hou, Mei, Zhang, Helong, Xiu, Qingyu, Zhu, Yunzhong, Feng, Jifeng, Qin, Shukui, Luo, Xiaoyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826513/
https://www.ncbi.nlm.nih.gov/pubmed/27061082
http://dx.doi.org/10.1186/s12885-016-2301-6
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author Sun, Yan
Cheng, Ying
Hao, Xuezhi
Wang, Jie
Hu, Chengping
Han, Baohui
Liu, Xiaoqing
Zhang, Li
Wan, Huiping
Xia, Zhongjun
Liu, Yunpeng
Li, Wei
Hou, Mei
Zhang, Helong
Xiu, Qingyu
Zhu, Yunzhong
Feng, Jifeng
Qin, Shukui
Luo, Xiaoyan
author_facet Sun, Yan
Cheng, Ying
Hao, Xuezhi
Wang, Jie
Hu, Chengping
Han, Baohui
Liu, Xiaoqing
Zhang, Li
Wan, Huiping
Xia, Zhongjun
Liu, Yunpeng
Li, Wei
Hou, Mei
Zhang, Helong
Xiu, Qingyu
Zhu, Yunzhong
Feng, Jifeng
Qin, Shukui
Luo, Xiaoyan
author_sort Sun, Yan
collection PubMed
description BACKGROUND: Extensive-disease small-cell lung cancer (ED-SCLC) is characterized by rapid progression and relapse, despite high initial response rates to chemotherapy. The primary objective of this trial was to demonstrate the non-inferiority of amrubicin and cisplatin (AP) combination therapy compared with the standard first-line regimen of etoposide and cisplatin (EP) for previously untreated ED-SCLC in a Chinese population. When non-inferiority was verified, the objective was switched from non-inferiority to superiority. METHODS: From June 2008 to July 2010, 300 patients were enrolled and randomly assigned at a 1:1 ratio to AP and EP groups. AP-treated patients received cisplatin (60 mg/m(2), day 1) and amrubicin (40 mg/m(2), days 1–3) once every 21 days. EP-treated patients received cisplatin (80 mg/m(2), day 1) and etoposide (100 mg/m(2), days 1–3) once every 21 days. Treatment was continued for four to six cycles, except in cases of progressive disease or toxicity, and patient refusal. RESULTS: Median overall survival (OS) for AP vs. EP treatment was 11.8 vs. 10.3 months (p = 0.08), respectively, demonstrating non-inferiority of AP to EP (AP group: 95 % confidence interval for hazard ratio 0.63–1.03 months). Median progression-free survival and overall response rates for AP vs. EP groups were 6.8 vs. 5.7 months (p = 0.35) and 69.8 % vs. 57.3 %, respectively. Drug-related adverse events in both groups were similar, with neutropenia being the most frequent (AP 54.4 %; EP 44.0 %). Leukopenia, pyrexia, and fatigue were more prevalent in the AP group, but all were clinically reversible and manageable. CONCLUSIONS: AP therapy demonstrated non-inferiority to EP therapy, prolonging OS for 1.5 months, but this difference was not statistically significant; thus we propose AP as a promising treatment option for ED-SCLC in China. TRIAL REGISTRATION: This trial was registered on 10 April 2008 (ClinicalTrials.gov NCT00660504). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2301-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-48265132016-04-10 Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer Sun, Yan Cheng, Ying Hao, Xuezhi Wang, Jie Hu, Chengping Han, Baohui Liu, Xiaoqing Zhang, Li Wan, Huiping Xia, Zhongjun Liu, Yunpeng Li, Wei Hou, Mei Zhang, Helong Xiu, Qingyu Zhu, Yunzhong Feng, Jifeng Qin, Shukui Luo, Xiaoyan BMC Cancer Research Article BACKGROUND: Extensive-disease small-cell lung cancer (ED-SCLC) is characterized by rapid progression and relapse, despite high initial response rates to chemotherapy. The primary objective of this trial was to demonstrate the non-inferiority of amrubicin and cisplatin (AP) combination therapy compared with the standard first-line regimen of etoposide and cisplatin (EP) for previously untreated ED-SCLC in a Chinese population. When non-inferiority was verified, the objective was switched from non-inferiority to superiority. METHODS: From June 2008 to July 2010, 300 patients were enrolled and randomly assigned at a 1:1 ratio to AP and EP groups. AP-treated patients received cisplatin (60 mg/m(2), day 1) and amrubicin (40 mg/m(2), days 1–3) once every 21 days. EP-treated patients received cisplatin (80 mg/m(2), day 1) and etoposide (100 mg/m(2), days 1–3) once every 21 days. Treatment was continued for four to six cycles, except in cases of progressive disease or toxicity, and patient refusal. RESULTS: Median overall survival (OS) for AP vs. EP treatment was 11.8 vs. 10.3 months (p = 0.08), respectively, demonstrating non-inferiority of AP to EP (AP group: 95 % confidence interval for hazard ratio 0.63–1.03 months). Median progression-free survival and overall response rates for AP vs. EP groups were 6.8 vs. 5.7 months (p = 0.35) and 69.8 % vs. 57.3 %, respectively. Drug-related adverse events in both groups were similar, with neutropenia being the most frequent (AP 54.4 %; EP 44.0 %). Leukopenia, pyrexia, and fatigue were more prevalent in the AP group, but all were clinically reversible and manageable. CONCLUSIONS: AP therapy demonstrated non-inferiority to EP therapy, prolonging OS for 1.5 months, but this difference was not statistically significant; thus we propose AP as a promising treatment option for ED-SCLC in China. TRIAL REGISTRATION: This trial was registered on 10 April 2008 (ClinicalTrials.gov NCT00660504). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2301-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-04-09 /pmc/articles/PMC4826513/ /pubmed/27061082 http://dx.doi.org/10.1186/s12885-016-2301-6 Text en © Sun et al. 2016 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 Research Article
Sun, Yan
Cheng, Ying
Hao, Xuezhi
Wang, Jie
Hu, Chengping
Han, Baohui
Liu, Xiaoqing
Zhang, Li
Wan, Huiping
Xia, Zhongjun
Liu, Yunpeng
Li, Wei
Hou, Mei
Zhang, Helong
Xiu, Qingyu
Zhu, Yunzhong
Feng, Jifeng
Qin, Shukui
Luo, Xiaoyan
Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer
title Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer
title_full Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer
title_fullStr Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer
title_full_unstemmed Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer
title_short Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer
title_sort randomized phase iii trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826513/
https://www.ncbi.nlm.nih.gov/pubmed/27061082
http://dx.doi.org/10.1186/s12885-016-2301-6
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