PMID- 24997137
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20211203
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 85
IP  - 3
DP  - 2014 Sep
TI  - Randomized phase II study of carboplatin and etoposide with or without obatoclax 
      mesylate in extensive-stage small cell lung cancer.
PG  - 420-8
LID - S0169-5002(14)00212-8 [pii]
LID - 10.1016/j.lungcan.2014.05.003 [doi]
AB  - OBJECTIVE: This randomized phase II study assessed the efficacy and safety of 
      obatoclax mesylate, a small-molecule Bcl-2 inhibitor, added to 
      carboplatin/etoposide chemotherapy as initial treatment for extensive-stage 
      small-cell lung cancer (ES-SCLC). MATERIALS AND METHODS: Chemotherapy-naive 
      subjects with ES-SCLC and Eastern Cooperative Oncology Group performance status 
      (ECOG PS) 0-2 received carboplatin/etoposide with (CbEOb) or without (CbE) 
      obatoclax for up to six cycles. Responders to CbEOb could receive maintenance 
      obatoclax until disease progression. The primary endpoint was objective response 
      rate (ORR). RESULTS: 155 subjects (median age 62, 58% male, 10% ECOG PS 2) were 
      treated with CbEOb (n=77) or CbE (n=78); 65% and 59% of subjects, respectively, 
      completed six cycles. ORR was 62% with CbEOb versus 53% with CbE (1-sided 
      p=0.143). Clinical benefit (ORR+ stable disease) trended better with CbEOb (81% 
      versus 68%; p=0.054). Median progression-free survival (PFS) and overall survival 
      (OS) were 5.8 months (95% confidence interval [CI]: 5.3-6.5) and 10.5 months 
      (8.9-13.8) with CbEOb and 5.2 months (95% CI: 4.1-5.7) and 9.8 months (7.2-11.2) 
      with CbE. Median OS was 10.5 months (95% CI: 8.9-13.8) and 9.8 months (7.2-11.2) 
      with a nonsignificant hazard ratio for OS, 0.823; 1-sided p=0.121. Grade 3/4 
      adverse events (AEs) were primarily hematologic and similar in frequency between 
      treatment arms. Obatoclax-related somnolence and euphoria were grade 1/2, 
      transient, and did not require treatment discontinuation. CONCLUSION: Obatoclax 
      was well tolerated when added to carboplatin/etoposide in first-line treatment of 
      ES-SCLC, but failed to significantly improve ORR, PFS, or OS.
CI  - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved.
FAU - Langer, Corey J
AU  - Langer CJ
AD  - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United 
      States. Electronic address: corey.langer@uphs.upenn.edu.
FAU - Albert, Istvan
AU  - Albert I
AD  - Matrai Gyogyintezet, Matrahaza, Hungary.
FAU - Ross, Helen J
AU  - Ross HJ
AD  - Mayo Clinic, Scottsdale, AZ, United States.
FAU - Kovacs, Peter
AU  - Kovacs P
AD  - University of Debrecen, Debrecen, Hungary.
FAU - Blakely, L Johnetta
AU  - Blakely LJ
AD  - The West Clinic, Memphis, TN, United States.
FAU - Pajkos, Gabor
AU  - Pajkos G
AD  - Bacs-Kiskun County Hospital, Kecskemet, Hungary.
FAU - Somfay, Attila
AU  - Somfay A
AD  - University of Szeged, Szeged, Hungary.
FAU - Zatloukal, Petr
AU  - Zatloukal P
AD  - Charles University, Faculty Hospital Bulovka and Postgraduate Medical Institute, 
      Prague, Czech Republic.
FAU - Kazarnowicz, Andrzej
AU  - Kazarnowicz A
AD  - Tuberculosis and Lung Disease Hospital, Olsztyn, Poland.
FAU - Moezi, Mehdi M
AU  - Moezi MM
AD  - Cancer Specialists of North Florida, Jacksonville, FL, United States.
FAU - Schreeder, Marshall T
AU  - Schreeder MT
AD  - Clearview Cancer Institute, Huntsville, AL, United States.
FAU - Schnyder, Judy
AU  - Schnyder J
AD  - Gemin X Pharmaceuticals, Malvern, PA, United States.
FAU - Ao-Baslock, Ada
AU  - Ao-Baslock A
AD  - Powered 4 Significance LLC, Bloomsbury, NJ, United States.
FAU - Pathak, Ashutosh K
AU  - Pathak AK
AD  - Teva Pharmaceuticals, Frazer, PA, United States.
FAU - Berger, Mark S
AU  - Berger MS
AD  - Gemin X Pharmaceuticals, Malvern, PA, United States.
CN  - GEM017 Investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT00682981
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140513
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Indoles)
RN  - 0 (Pyrroles)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - BG3F62OND5 (Carboplatin)
RN  - QN4128B52A (obatoclax)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Carboplatin/administration & dosage
MH  - Comorbidity
MH  - Etoposide/administration & dosage
MH  - Female
MH  - Humans
MH  - Indoles
MH  - Lung Neoplasms/*drug therapy/mortality/*pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - Pyrroles/administration & dosage
MH  - Small Cell Lung Carcinoma/*drug therapy/mortality/*pathology
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Bcl-2
OT  - Carboplatin
OT  - Etoposide
OT  - Obatoclax
OT  - Randomized
OT  - SCLC
EDAT- 2014/07/06 06:00
MHDA- 2015/05/12 06:00
CRDT- 2014/07/06 06:00
PHST- 2014/02/14 00:00 [received]
PHST- 2014/04/30 00:00 [revised]
PHST- 2014/05/06 00:00 [accepted]
PHST- 2014/07/06 06:00 [entrez]
PHST- 2014/07/06 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
AID - S0169-5002(14)00212-8 [pii]
AID - 10.1016/j.lungcan.2014.05.003 [doi]
PST - ppublish
SO  - Lung Cancer. 2014 Sep;85(3):420-8. doi: 10.1016/j.lungcan.2014.05.003. Epub 2014 
      May 13.