TY - JOUR
T1 - Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer
AU - Sun, Yan
AU - Cheng, Ying
AU - Hao, Xuezhi
AU - Wang, Jie
AU - Hu, Chengping
AU - Han, Baohui
AU - Liu, Xiaoqing
AU - Zhang, Li
AU - Wan, Huiping
AU - Xia, Zhongjun
AU - Liu, Yunpeng
AU - Li, Wei
AU - Hou, Mei
AU - Zhang, Helong
AU - Xiu, Qingyu
AU - Zhu, Yunzhong
AU - Feng, Jifeng
AU - Qin, Shukui
AU - Luo, Xiaoyan
N1 - Funding Information:
This study was supported by Sumitomo Pharmaceuticals (Suzhou) Co., Ltd.
Publisher Copyright:
© 2016 Sun et al.
PY - 2016/4/9
Y1 - 2016/4/9
N2 - 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/m2, day 1) and amrubicin (40 mg/m2, days 1-3) once every 21 days. EP-treated patients received cisplatin (80 mg/m2, day 1) and etoposide (100 mg/m2, 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 ).
AB - 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/m2, day 1) and amrubicin (40 mg/m2, days 1-3) once every 21 days. EP-treated patients received cisplatin (80 mg/m2, day 1) and etoposide (100 mg/m2, 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 ).
KW - Amrubicin
KW - Chinese
KW - Cisplatin
KW - ED-SCLC
KW - Etoposide
KW - Randomized clinical trial
UR - http://www.scopus.com/inward/record.url?scp=84962888106&partnerID=8YFLogxK
U2 - 10.1186/s12885-016-2301-6
DO - 10.1186/s12885-016-2301-6
M3 - Article
C2 - 27061082
AN - SCOPUS:84962888106
VL - 16
JO - BMC Cancer
JF - BMC Cancer
SN - 1471-2407
IS - 1
M1 - 265
ER -