title: Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer.
abstract: 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.
  
  
  BACKGROUND
  This trial was registered on 10 April 2008 (ClinicalTrials.gov NCT00660504).
authors.affiliation: Department of Internal Medicine, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. suny@csco.org.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine, Jilin Cancer Hospital, Jilin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Internal Medicine, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Hao
authors.affiliation: Department of Medical Oncology, Beijing Cancer Hospital, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital of Central-South University, Hunan, China.
authors.forename: Chengping
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai, China.
authors.forename: Baohui
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Lung Cancer Medicine, 307th Hospital of the Chinese People's Liberation Army, Beijing, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Jiangxi Provincial People's Hospital, Jiangxi, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Wan
authors.affiliation: Department of Medical Oncology, Affiliated Cancer Hospital of Sun Yat-sen University, Guangdong, China.
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Liaoning, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, The First Hospital of Jilin University, Jilin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, West China Hospital, Sichuan University, Sichuan, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Hou
authors.affiliation: Department of Medical Oncology, Tangdu Hospital of the Fourth Military Medical University, Shanxi, China.
authors.forename: Helong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai Changzheng Hospital, Shanghai, China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Xiu
authors.affiliation: Department of Medical Oncology, Beijing Chest Hospital, Beijing, China.
authors.forename: Yunzhong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu, China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Medical Oncology, 81st Hospital of the Chinese People's Liberation Army, Jiangsu, China.
authors.forename: Shukui
authors.initials: S
authors.lastname: Qin
authors.affiliation: Medical Division, Sumitomo Pharmaceuticals (Suzhou) Co., Ltd., Beijing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Luo
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D002681:China; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018943:Anthracyclines; D005047:Etoposide; C055866:amrubicin; D002945:Cisplatin
keywords: Amrubicin; Chinese; Cisplatin; ED-SCLC; Etoposide; Randomized clinical trial