PMID- 21709202
OWN - NLM
STAT- MEDLINE
DCOM- 20110816
LR  - 20240109
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 29
IP  - 22
DP  - 2011 Aug 1
TI  - Randomized phase III placebo-controlled trial of carboplatin and paclitaxel with 
      or without the vascular disrupting agent vadimezan (ASA404) in advanced 
      non-small-cell lung cancer.
PG  - 2965-71
LID - 10.1200/JCO.2011.35.0660 [doi]
AB  - PURPOSE: This phase III trial was conducted to test whether the novel vascular 
      disrupting agent ASA404 (vadimezan), when combined with first-line platinum-based 
      chemotherapy, improves survival in patients with advanced non-small-cell lung 
      cancer (NSCLC) versus chemotherapy alone. PATIENTS AND METHODS: Patients with 
      advanced stage IIIB or IV NSCLC, stratified by sex and tumor histology, were 
      randomly assigned 1:1 to paclitaxel (200 mg/m(2)) and carboplatin (area under the 
      curve, 6.0) with or without ASA404 (1,800 mg m(2)), given intravenously once 
      every 3 weeks for six cycles followed by maintenance ASA404 or placebo. Primary 
      end point was overall survival (OS); secondary end points included overall 
      response rate (ORR) and progression-free survival (PFS). RESULTS: One thousand 
      two hundred ninety-nine patients were randomly assigned. The trial was stopped 
      for futility at interim analysis. At final analysis, there was no difference in 
      OS seen between ASA404 (n = 649) and placebo (n = 650) arms: median OS was 13.4 
      and 12.7 months respectively (hazard ratio [HR], 1.01; 95% CI, 0.85 to 1.19; P = 
      .535). Similarly, no OS difference was seen in the histologic (squamous or 
      nonsquamous) and sex (male or female) strata. Median PFS was 5.5 months in both 
      arms (HR, 1.04; P = .727), while ORR was 25% in both arms (P = 1.0). Overall rate 
      of adverse events (AEs) was comparable between the ASA404 and placebo arms. Grade 
      4 neutropenia (27% v 19%) and infusion site pain (10% v 0.5%) were reported more 
      frequently in the ASA404 arm. CONCLUSION: The addition of ASA404 to carboplatin 
      and paclitaxel, although generally well tolerated, failed to improve frontline 
      efficacy in advanced NSCLC.
FAU - Lara, Primo N Jr
AU  - Lara PN Jr
AD  - University of California, Davis Cancer Center, 4501 X St, Suite 3016, Sacramento, 
      CA, USA. primo.lara@ucdmc.ucdavis.edu
FAU - Douillard, Jean-Yves
AU  - Douillard JY
FAU - Nakagawa, Kazuhiko
AU  - Nakagawa K
FAU - von Pawel, Joachim
AU  - von Pawel J
FAU - McKeage, Mark J
AU  - McKeage MJ
FAU - Albert, Istvan
AU  - Albert I
FAU - Losonczy, Gyorgy
AU  - Losonczy G
FAU - Reck, Martin
AU  - Reck M
FAU - Heo, Dae-Seog
AU  - Heo DS
FAU - Fan, Xiaolin
AU  - Fan X
FAU - Fandi, Abderrahim
AU  - Fandi A
FAU - Scagliotti, Giorgio
AU  - Scagliotti G
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20110627
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 (Angiogenesis Inhibitors)
RN  - 0 (Xanthones)
RN  - 0829J8133H (vadimezan)
RN  - BG3F62OND5 (Carboplatin)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
CIN - J Clin Oncol. 2011 Aug 1;29(22):2952-5. PMID: 21709201
CIN - J Clin Oncol. 2012 Mar 1;30(7):760-1; author reply 761-3. PMID: 22291088
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/administration & dosage/adverse effects/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Carboplatin/administration & dosage
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/*mortality/secondary
MH  - Disease-Free Survival
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*drug therapy/*mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Odds Ratio
MH  - Paclitaxel/administration & dosage
MH  - Quality of Life
MH  - Surveys and Questionnaires
MH  - Treatment Failure
MH  - Xanthones/administration & dosage/adverse effects/*therapeutic use
EDAT- 2011/06/29 06:00
MHDA- 2011/08/17 06:00
CRDT- 2011/06/29 06:00
PHST- 2011/06/29 06:00 [entrez]
PHST- 2011/06/29 06:00 [pubmed]
PHST- 2011/08/17 06:00 [medline]
AID - JCO.2011.35.0660 [pii]
AID - 10.1200/JCO.2011.35.0660 [doi]
PST - ppublish
SO  - J Clin Oncol. 2011 Aug 1;29(22):2965-71. doi: 10.1200/JCO.2011.35.0660. Epub 2011 
      Jun 27.