PMID- 29134432
OWN - NLM
STAT- MEDLINE
DCOM- 20190125
LR  - 20190125
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 36
IP  - 2
DP  - 2018 Apr
TI  - Phase III study of dulanermin (recombinant human tumor necrosis factor-related 
      apoptosis-inducing ligand/Apo2 ligand) combined with vinorelbine and cisplatin in 
      patients with advanced non-small-cell lung cancer.
PG  - 315-322
LID - 10.1007/s10637-017-0536-y [doi]
AB  - Background Dulanermin is a recombinant soluble human Apo2 ligand/tumor necrosis 
      factor-related apoptosis-inducing ligand (TRAIL) that activates apoptotic 
      pathways by binding to proapoptotic death receptor (DR) 4 and DR5. The purpose of 
      this study was to evaluate the efficacy and safety of dulanermin combined with 
      vinorelbine and cisplatin (NP) as the first-line treatment for patients with 
      advanced non-small-cell lung cancer (NSCLC). Experimental design Patients were 
      randomly assigned to receive NP chemotherapy (vinorelbine 25 mg/m(2) on days 1 
      and 8 and cisplatin 30 mg/m(2) on days 2 to 4) for up to six cycles plus 
      dulanermin (75 mug/kg on days 1 to 14) or placebo every three weeks until disease 
      progression, intolerable toxicity, or withdrawal of consent. The primary end 
      point was progression-free survival (PFS), and the secondary end points included 
      objective response rate (ORR), overall survival (OS), and safety evaluation. 
      Results Between October 2009 and June 2012, 452 untreated patients with stage 
      IIIB to IV NSCLC were randomly assigned to receive dulanermin plus NP (n = 342) 
      and placebo plus NP (n = 110). Median PFS was 6.4 months in the dulanermin arm 
      versus 3.5 months in the placebo arm (hazard ratio (HR), 0.4034; 95% CI, 0.3181 
      to 0.5117, p < 0.0001). ORR was 46.78% in the dulanermin arm versus 30.00% in the 
      placebo arm (p = 0.0019). Median OS was 14.6 months in the dulanermin arm versus 
      13.9 months in the placebo arm (HR, 0.94; 95% CI, 0.74 to 1.21, p = 0.64). The 
      most common grade >/= 3 adverse events (AEs) were oligochromemia, leukopenia, 
      neutropenia, and oligocythemia. Overall incidence of AEs, grade >/= 3 AEs, and 
      serious AEs were similar across the two arms. Conclusion Addition of dulanermin 
      to the NP regimen significantly improved PFS and ORR. However, our results showed 
      that the combination of dulanermin with chemotherapy had a synergic activity and 
      favorable toxic profile in the treatment of patients with advanced NSCLC.
FAU - Ouyang, Xuenong
AU  - Ouyang X
AD  - Department of Medical Oncology, Fuzhou General Hospital of Nanjing Military 
      Command, Fuzong Clinical College, Fujian Medical University, Fuzhou, China.
FAU - Shi, Meiqi
AU  - Shi M
AD  - Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of 
      Cancer Research, Nanjing Medical University affiliated Cancer Hospital, No.42 
      Baiziting, Xuanwu District, Nanjing, Jiangsu,, 210009, China.
FAU - Jie, Fangwei
AU  - Jie F
AD  - Department of Medical Oncology, Fuzhou General Hospital of Nanjing Military 
      Command, Fuzong Clinical College, Fujian Medical University, Fuzhou, China.
FAU - Bai, Yuxian
AU  - Bai Y
AD  - Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin 
      Medical University, Harbin, China.
FAU - Shen, Peng
AU  - Shen P
AD  - Department of Medical Oncology, First Affiliated Hospital, Zhejiang University 
      School of Medicine, Hangzhou, China.
FAU - Yu, Zhuang
AU  - Yu Z
AD  - Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
FAU - Wang, Xiuwen
AU  - Wang X
AD  - Department of Chemotherapy, Qilu Hospital of Shandong University, Jinan, 
      Shandong, China.
FAU - Huang, Cheng
AU  - Huang C
AD  - Department of Medical Oncology, Fujian Provincial Cancer Hospital, The Teaching 
      Hospital of Fujian Medical University, The Teaching Hospital of Fujian University 
      of Traditional Chinese Medicine, Fuzhou, China.
FAU - Tao, Min
AU  - Tao M
AD  - Department of Oncology, The First Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Wang, Zhehai
AU  - Wang Z
AD  - Department of internal Medicine-Oncology, Shandong Cancer Hospital and Institute, 
      Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of 
      Medical Sciences, Jinan, China.
FAU - Xie, Conghua
AU  - Xie C
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Wuhan, Hubei, China.
FAU - Wu, Qi
AU  - Wu Q
AD  - Department of Oncology, Sichuan Academy of Medical Sciences & Sichuan Provincial 
      People's Hospital, Chengdu, Sichuan, China.
FAU - Shu, Yongqian
AU  - Shu Y
AD  - Department of Oncology, Jiangsu Proving Hospital, The First Affiliated Hospital 
      of Nanjing Medical University, Nanjing, Jiangsu, China.
FAU - Han, Baohui
AU  - Han B
AD  - Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Zhang, Fengchun
AU  - Zhang F
AD  - Department of Oncology, Renji Hospital Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Zhang, Yiping
AU  - Zhang Y
AD  - Department of Medical Oncology, Zhejiang Cancer Hospital, Zhejiang, Hangzhou, 
      China.
FAU - Hu, Chunhong
AU  - Hu C
AD  - Department of Oncology, The Second Xiangya Hospital of Central South University, 
      Changsha, Hunan, China.
FAU - Ma, Xitao
AU  - Ma X
AD  - Department of Respiratory and Critical Care Medicine, Henan Provincial People's 
      Hospital, Zhengzhou, Henan, China.
FAU - Liang, Yongjie
AU  - Liang Y
AD  - Department of Respiratory Medicine, Shanghai East Hospital, Tongji University, 
      Shanghai, China.
FAU - Wang, Anlan
AU  - Wang A
AD  - Department of Medical Oncology, Hunan Cancer Hospital, Changsha, Hunan, China.
FAU - Lu, Bing
AU  - Lu B
AD  - Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji 
      University School of Medicine, Shanghai, China.
FAU - Shi, Yi
AU  - Shi Y
AD  - Department of Respiratory Medicine, Nanjing General Hospital of Nanjing Military 
      Command, Nanjing, Jiangsu, China.
FAU - Chen, Jinfei
AU  - Chen J
AD  - Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - Zhuang, Zhixiang
AU  - Zhuang Z
AD  - Department of Oncology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, China.
FAU - Wang, Jiejun
AU  - Wang J
AD  - Department of Medical Oncology, Changzheng Hospital, Shanghai, China.
FAU - Huang, Jianjin
AU  - Huang J
AD  - Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Wang, Changhui
AU  - Wang C
AD  - Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji 
      University, Shanghai, China.
FAU - Bai, Chunxue
AU  - Bai C
AD  - Department of Respiratory Medicine, Zhongshan Hospital Affiliated to Fudan 
      University, Shanghai, China.
FAU - Zhou, Xin
AU  - Zhou X
AD  - Department of Respiratory, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Li, Qiang
AU  - Li Q
AD  - Department of Respiratory Medicine, Changhai Hospital, The Second Military 
      Medical University, Shanghai, China.
FAU - Chen, Feng
AU  - Chen F
AD  - Department of Epidemiology and Biostatistics, School of Public Health, Nanjing 
      Medical University, Nanjing, Jiangsu, China.
FAU - Yu, Hao
AU  - Yu H
AD  - Department of Epidemiology and Biostatistics, School of Public Health, Nanjing 
      Medical University, Nanjing, Jiangsu, China.
FAU - Feng, Jifeng
AU  - Feng J
AD  - Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of 
      Cancer Research, Nanjing Medical University affiliated Cancer Hospital, No.42 
      Baiziting, Xuanwu District, Nanjing, Jiangsu,, 210009, China. fjifeng@126.com.
LA  - eng
GR  - 08431901100/Shanghai biomedical technology fund/International
GR  - 10C26213100701/National sme funding fund/International
GR  - 2010ZX09401-301/National major science and technology project fund/International
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20171114
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - Q20Q21Q62J (Cisplatin)
RN  - Q6C979R91Y (Vinorelbine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology
MH  - Cisplatin/adverse effects/*therapeutic use
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - TNF-Related Apoptosis-Inducing Ligand/adverse effects/*therapeutic use
MH  - Treatment Outcome
MH  - Vinorelbine/adverse effects/*therapeutic use
MH  - Young Adult
OTO - NOTNLM
OT  - Dulanermin
OT  - NSCLC
OT  - Objective response rate
OT  - Phase III
OT  - Progression-free survival
EDAT- 2017/11/15 06:00
MHDA- 2019/01/27 06:00
CRDT- 2017/11/15 06:00
PHST- 2017/07/13 00:00 [received]
PHST- 2017/10/30 00:00 [accepted]
PHST- 2017/11/15 06:00 [pubmed]
PHST- 2019/01/27 06:00 [medline]
PHST- 2017/11/15 06:00 [entrez]
AID - 10.1007/s10637-017-0536-y [pii]
AID - 10.1007/s10637-017-0536-y [doi]
PST - ppublish
SO  - Invest New Drugs. 2018 Apr;36(2):315-322. doi: 10.1007/s10637-017-0536-y. Epub 
      2017 Nov 14.