PMID- 19692680
OWN - NLM
STAT- MEDLINE
DCOM- 20090909
LR  - 20250214
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 361
IP  - 10
DP  - 2009 Sep 3
TI  - Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.
PG  - 947-57
LID - 10.1056/NEJMoa0810699 [doi]
AB  - BACKGROUND: Previous, uncontrolled studies have suggested that first-line 
      treatment with gefitinib would be efficacious in selected patients with 
      non-small-cell lung cancer. METHODS: In this phase 3, open-label study, we 
      randomly assigned previously untreated patients in East Asia who had advanced 
      pulmonary adenocarcinoma and who were nonsmokers or former light smokers to 
      receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose 
      calculated to produce an area under the curve of 5 or 6 mg per milliliter per 
      minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 
      patients). The primary end point was progression-free survival. RESULTS: The 
      12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% 
      with carboplatin-paclitaxel. The study met its primary objective of showing the 
      noninferiority of gefitinib and also showed its superiority, as compared with 
      carboplatin-paclitaxel, with respect to progression-free survival in the 
      intention-to-treat population (hazard ratio for progression or death, 0.74; 95% 
      confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients 
      who were positive for the epidermal growth factor receptor gene (EGFR) mutation, 
      progression-free survival was significantly longer among those who received 
      gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for 
      progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the 
      subgroup of 176 patients who were negative for the mutation, progression-free 
      survival was significantly longer among those who received carboplatin-paclitaxel 
      (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 
      3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of 
      patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects 
      (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin-paclitaxel 
      group. CONCLUSIONS: Gefitinib is superior to carboplatin-paclitaxel as an initial 
      treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers 
      in East Asia. The presence in the tumor of a mutation of the EGFR gene is a 
      strong predictor of a better outcome with gefitinib. (ClinicalTrials.gov number, 
      NCT00322452.)
CI  - 2009 Massachusetts Medical Society
FAU - Mok, Tony S
AU  - Mok TS
AD  - State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, 
      Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong. 
      tony@clo.cuhk.edu.hk
FAU - Wu, Yi-Long
AU  - Wu YL
FAU - Thongprasert, Sumitra
AU  - Thongprasert S
FAU - Yang, Chih-Hsin
AU  - Yang CH
FAU - Chu, Da-Tong
AU  - Chu DT
FAU - Saijo, Nagahiro
AU  - Saijo N
FAU - Sunpaweravong, Patrapim
AU  - Sunpaweravong P
FAU - Han, Baohui
AU  - Han B
FAU - Margono, Benjamin
AU  - Margono B
FAU - Ichinose, Yukito
AU  - Ichinose Y
FAU - Nishiwaki, Yutaka
AU  - Nishiwaki Y
FAU - Ohe, Yuichiro
AU  - Ohe Y
FAU - Yang, Jin-Ji
AU  - Yang JJ
FAU - Chewaskulyong, Busyamas
AU  - Chewaskulyong B
FAU - Jiang, Haiyi
AU  - Jiang H
FAU - Duffield, Emma L
AU  - Duffield EL
FAU - Watkins, Claire L
AU  - Watkins CL
FAU - Armour, Alison A
AU  - Armour AA
FAU - Fukuoka, Masahiro
AU  - Fukuoka M
LA  - eng
SI  - ClinicalTrials.gov/NCT00322452
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20090819
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolines)
RN  - BG3F62OND5 (Carboplatin)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - P88XT4IS4D (Paclitaxel)
RN  - S65743JHBS (Gefitinib)
SB  - IM
CIN - N Engl J Med. 2009 Sep 3;361(10):1018-20. doi: 10.1056/NEJMe0905763. PMID: 
      19692681
CIN - N Engl J Med. 2009 Dec 17;361(25):2485; author reply 2486-7. doi: 
      10.1056/NEJMc0909634. PMID: 20018971
CIN - N Engl J Med. 2009 Dec 17;361(25):2485; author reply 2486-7. PMID: 20050212
CIN - N Engl J Med. 2009 Dec 17;361(25):2485-6; author reply 2486-7. PMID: 20050213
MH  - Adenocarcinoma/*drug therapy/genetics/mortality
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/adverse effects/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Carboplatin/adverse effects/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy
MH  - Disease-Free Survival
MH  - ErbB Receptors/antagonists & inhibitors/*genetics
MH  - Female
MH  - Gefitinib
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*drug therapy/genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Paclitaxel/adverse effects/*therapeutic use
MH  - Proportional Hazards Models
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Quinazolines/adverse effects/*therapeutic use
EDAT- 2009/08/21 09:00
MHDA- 2009/09/10 06:00
CRDT- 2009/08/21 09:00
PHST- 2009/08/21 09:00 [entrez]
PHST- 2009/08/21 09:00 [pubmed]
PHST- 2009/09/10 06:00 [medline]
AID - NEJMoa0810699 [pii]
AID - 10.1056/NEJMoa0810699 [doi]
PST - ppublish
SO  - N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 
      Aug 19.