PMID- 21464154
OWN - NLM
STAT- MEDLINE
DCOM- 20120411
LR  - 20240229
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 23
IP  - 1
DP  - 2012 Jan
TI  - A phase III randomized study of gemcitabine and cisplatin with or without 
      PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung 
      cancer.
PG  - 72-77
LID - S0923-7534(19)39028-3 [pii]
LID - 10.1093/annonc/mdr030 [doi]
AB  - BACKGROUND: This open-label phase III study assessed the addition of Toll-like 
      receptor 9-activating oligodeoxynucleotide PF-3512676 to gemcitabine/cisplatin 
      chemotherapy in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND 
      METHODS: Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomized 
      (1:1) to receive six or fewer 3-week cycles of i.v. gemcitabine (1250 mg/m2 on 
      days 1 and 8) and cisplatin alone (75 mg/m2 on day 1, control arm) or combined 
      with s.c. PF-3512676 0.2 mg/kg on days 8 and 15 of each chemotherapy cycle and 
      weekly thereafter until progression or unacceptable toxicity (experimental arm). 
      No crossover was planned. The primary end point was overall survival (OS). 
      RESULTS: A total of 839 patients were randomized. Baseline demographics were well 
      balanced. Median OS (11.0 versus 10.7 months; P=0.98) and median progression-free 
      survival (PFS) (both 5.1 months) were similar between groups. Grade>/=3 hematologic 
      adverse events (AEs), injection-site reactions, and influenza-like symptoms were 
      more frequently reported among patients receiving PF-3512676. At the 
      first-interim analysis, the Data Safety Monitoring Committee recommended study 
      discontinuation. Administration of PF-3512676 was halted based on efficacy 
      futility and increased grade>/=3 AEs (experimental arm). CONCLUSIONS: Addition of 
      PF-3512676 to gemcitabine/cisplatin chemotherapy did not improve OS or PFS but 
      did increase toxicity.
FAU - Manegold, C
AU  - Manegold C
AD  - Interdisciplinary Thoracic Oncology, Department of Surgery, University Medical 
      Center Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: 
      Prof.Manegold@t-online.de.
FAU - van Zandwijk, N
AU  - van Zandwijk N
AD  - Bernie Banton Centre, University of Sydney, Sydney, Australia.
FAU - Szczesna, A
AU  - Szczesna A
AD  - 3rd Department, Regional Lung Diseases Hospital, Otwock, Poland.
FAU - Zatloukal, P
AU  - Zatloukal P
AD  - 3rd Faculty of Medicine, Charles University, Faculty Hospital Bulovka and 
      Postgraduate Medical Institute, Prague, Czech Republic.
FAU - Au, J S K
AU  - Au JSK
AD  - Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong.
FAU - Blasinska-Morawiec, M
AU  - Blasinska-Morawiec M
AD  - Department of Proliferative Diseases, Copernicus Memorial Hospital, Lodz.
FAU - Serwatowski, P
AU  - Serwatowski P
AD  - Chemotherapy Department, Specialistic Hospital Named After Professor A. 
      Sokolowski, Szczecin-Zdunowo.
FAU - Krzakowski, M
AU  - Krzakowski M
AD  - Lung and Thoracic Tumours Department, Maria Sklodowska-Curie Memorial Cancer 
      Centre, Warsaw.
FAU - Jassem, J
AU  - Jassem J
AD  - Department of Oncology and Radiology, Medical University of Gdansk, Gdansk, 
      Poland.
FAU - Tan, E H
AU  - Tan EH
AD  - Department of Medical Oncology, National Cancer Centre, Singapore.
FAU - Benner, R J
AU  - Benner RJ
AD  - Pfizer Global Research and Development, New London, USA.
FAU - Ingrosso, A
AU  - Ingrosso A
AD  - Pfizer Global Research and Development, Milan, Italy.
FAU - Meech, S J
AU  - Meech SJ
AD  - Pfizer Global Research and Development, New London, USA.
FAU - Readett, D
AU  - Readett D
AD  - Pfizer Global Research and Development, New London, USA.
FAU - Thatcher, N
AU  - Thatcher N
AD  - Department of Medical Oncology, Christie Hospital, Manchester, UK.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20110404
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (ProMune)
RN  - 0W860991D6 (Deoxycytidine)
RN  - Q20Q21Q62J (Cisplatin)
RN  - 0 (Gemcitabine)
SB  - IM
CIN - Ann Oncol. 2012 Jan;23(1):7-9. PMID: 22190670
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality
MH  - Cisplatin/administration & dosage/adverse effects
MH  - Deoxycytidine/administration & dosage/adverse effects/analogs & derivatives
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*drug therapy/mortality
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Oligodeoxyribonucleotides/*administration & dosage/adverse effects
MH  - Proportional Hazards Models
MH  - Gemcitabine
EDAT- 2011/04/06 06:00
MHDA- 2012/04/12 06:00
CRDT- 2011/04/06 06:00
PHST- 2011/04/06 06:00 [entrez]
PHST- 2011/04/06 06:00 [pubmed]
PHST- 2012/04/12 06:00 [medline]
AID - S0923-7534(19)39028-3 [pii]
AID - 10.1093/annonc/mdr030 [doi]
PST - ppublish
SO  - Ann Oncol. 2012 Jan;23(1):72-77. doi: 10.1093/annonc/mdr030. Epub 2011 Apr 4.