PMID- 21632509
OWN - NLM
STAT- MEDLINE
DCOM- 20110906
LR  - 20210103
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 29
IP  - 19
DP  - 2011 Jul 1
TI  - Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 
      (Toll-like receptor 9 agonist) as first-line treatment for advanced 
      non-small-cell lung cancer.
PG  - 2667-74
LID - 10.1200/JCO.2010.32.8971 [doi]
AB  - PURPOSE: This phase III study examined efficacy of the synthetic Toll-like 
      receptor 9-activating oligodeoxynucleotide PF-3512676 in combination with 
      standard paclitaxel/carboplatin chemotherapy in patients with advanced 
      non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive 
      patients with stage IIIB or IV NSCLC were randomly assigned (1:1) to receive up 
      to six courses of paclitaxel/carboplatin (intravenous paclitaxel 200 mg/m(2) and 
      carboplatin at area under the [concentration-time] curve 6 on day 1 of a 3-week 
      cycle) alone (control arm) or in combination with 0.2 mg/kg subcutaneous 
      PF-3512676 on days 8 and 15 (investigational arm). Primary end point was overall 
      survival (OS). RESULTS: Baseline demographics were similar across arms (N = 828). 
      Most patients (88%) had stage IV disease. Median OS and median progression-free 
      survival (PFS) were similar (OS: investigational arm, 10.0 months v control arm, 
      9.8 months; P = .56; PFS: investigational arm, 4.8 months v control arm, 4.7 
      months; P = .79). Most commonly reported PF-3512676-related adverse events (AEs) 
      were mild-to-moderate local injection site reactions, pyrexia, and flu-like 
      symptoms. In the investigational arm, grades 3 to 4 AEs, including neutropenia, 
      thrombocytopenia, and anemia, were more frequent, and more patients had one or 
      more sepsis-related AEs versus controls (17 v 3). At first interim analysis, the 
      Data Safety Monitoring Committee recommended study discontinuation because of 
      lack of incremental efficacy and more sepsis-related serious AEs in the 
      PF-3512676 arm. Administration of PF-3512676, but not chemotherapy, was halted. 
      CONCLUSION: Addition of PF-3512676 to paclitaxel/carboplatin did not improve OS 
      or PFS versus paclitaxel/carboplatin alone for first-line treatment of patients 
      with advanced NSCLC but did increase toxicity. This regimen cannot be recommended 
      for treating patients with advanced NSCLC.
FAU - Hirsh, Vera
AU  - Hirsh V
AD  - McGill University Health Center, Royal Victoria Hospital, Montreal, QC, Canada. 
      vera.hirsh@muhc.mcgill.ca
FAU - Paz-Ares, Luis
AU  - Paz-Ares L
FAU - Boyer, Michael
AU  - Boyer M
FAU - Rosell, Rafael
AU  - Rosell R
FAU - Middleton, Gary
AU  - Middleton G
FAU - Eberhardt, Wilfried E E
AU  - Eberhardt WE
FAU - Szczesna, Aleksandra
AU  - Szczesna A
FAU - Reiterer, Pavel
AU  - Reiterer P
FAU - Saleh, Mansoor
AU  - Saleh M
FAU - Arrieta, Oscar
AU  - Arrieta O
FAU - Bajetta, Emilio
AU  - Bajetta E
FAU - Webb, Roy T
AU  - Webb RT
FAU - Raats, Johannes
AU  - Raats J
FAU - Benner, Rebecca J
AU  - Benner RJ
FAU - Fowst, Camilla
AU  - Fowst C
FAU - Meech, Sandra J
AU  - Meech SJ
FAU - Readett, David
AU  - Readett D
FAU - Schiller, Joan H
AU  - Schiller JH
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20110531
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (ProMune)
RN  - 0 (Toll-Like Receptor 9)
RN  - BG3F62OND5 (Carboplatin)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Carboplatin/*administration & dosage
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Oligodeoxyribonucleotides/*administration & dosage
MH  - Paclitaxel/*administration & dosage
MH  - Toll-Like Receptor 9/*agonists
MH  - Treatment Outcome
EDAT- 2011/06/03 06:00
MHDA- 2011/09/07 06:00
CRDT- 2011/06/03 06:00
PHST- 2011/06/03 06:00 [entrez]
PHST- 2011/06/03 06:00 [pubmed]
PHST- 2011/09/07 06:00 [medline]
AID - JCO.2010.32.8971 [pii]
AID - 10.1200/JCO.2010.32.8971 [doi]
PST - ppublish
SO  - J Clin Oncol. 2011 Jul 1;29(19):2667-74. doi: 10.1200/JCO.2010.32.8971. Epub 2011 
      May 31.