PMID- 23033932
OWN - NLM
STAT- MEDLINE
DCOM- 20130523
LR  - 20211021
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 12
DP  - 2012 Oct 3
TI  - A Phase II study of pulse dose imatinib mesylate and weekly paclitaxel in 
      patients aged 70 and over with advanced non-small cell lung cancer.
PG  - 449
LID - 10.1186/1471-2407-12-449 [doi]
AB  - BACKGROUND: In non-small cell lung cancer (NSCLC), interstitial hypertension is a 
      barrier to chemotherapy delivery, and is mediated by platelet derived growth 
      factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve 
      intra-tumoral delivery of paclitaxel, increasing response rate (RR). METHODS: 
      This single-stage, open-label phase II study evaluated pulse dose imatinib and 
      weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were 
      aged >/= 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. 
      Primary endpoint was RR. Secondary endpoints included median progression free and 
      overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline 
      Charlson Comorbidity Index (CCI) and Vulnerable Elder Survey-13 (VES-13) were 
      correlated with outcomes. RESULTS: Thirty-four patients with median age 75 
      enrolled. Eleven of 29 (38%) were frail by VES-13 score. Overall RR was 11/34 
      (32%; 95% CI 17%-51%), meeting the primary endpoint. Median PFS and OS were 3.6 
      and 7.3 months, respectively. High tumoral PDGF-B expression predicted inferior 
      PFS. Frail patients by VES-13 had significantly worse median PFS (3.2 vs. 4.5 
      months; p=0.02) and OS (4.8 vs. 12 months; p=0.02) than non-frail. CONCLUSIONS: 
      The combination of imatinib and paclitaxel had encouraging activity as measured 
      by the primary endpoint of RR. However, PFS and OS were typical for elderly 
      patients treated with single agent chemotherapy and the regimen is not 
      recommended for further study. Adjunct imatinib did not overcome the established 
      association of tumoral PDGF-B expression with inferior PFS. VES-13 was a powerful 
      predictor of poor survival outcomes. Frailty should be further studied as a 
      predictor of non-benefit from chemotherapy. TRIAL REGISTRATION: 
      ClinicalTrials.gov NCT01011075.
FAU - Bauman, Julie E
AU  - Bauman JE
AD  - Department of Internal Medicine, Division of Hematology/Oncology and 
      Biostatistics, University of New Mexico Cancer Center, Albuquerque, New Mexico, 
      USA. baumanje@upmc.edu
FAU - Eaton, Keith D
AU  - Eaton KD
FAU - Wallace, Sarah G
AU  - Wallace SG
FAU - Carr, Laurie L
AU  - Carr LL
FAU - Lee, Sang-Joon
AU  - Lee SJ
FAU - Jones, Dennie V
AU  - Jones DV
FAU - Arias-Pulido, Hugo
AU  - Arias-Pulido H
FAU - Cerilli, Lisa A
AU  - Cerilli LA
FAU - Martins, Renato G
AU  - Martins RG
LA  - eng
SI  - ClinicalTrials.gov/NCT01011075
GR  - 2P30CA118100/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121003
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Proto-Oncogene Proteins c-sis)
RN  - 0 (Pyrimidines)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (Receptors, Platelet-Derived Growth Factor)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Benzamides/administration & dosage/adverse effects
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Fatigue/chemically induced
MH  - Female
MH  - Frail Elderly
MH  - Humans
MH  - Imatinib Mesylate
MH  - Lung/*drug effects/metabolism/pathology
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Neoplasm Staging
MH  - Neutropenia/chemically induced
MH  - Paclitaxel/administration & dosage/adverse effects
MH  - Piperazines/administration & dosage/adverse effects
MH  - Proto-Oncogene Proteins c-sis/metabolism
MH  - Pyrimidines/administration & dosage/adverse effects
MH  - Receptors, Platelet-Derived Growth Factor/antagonists & inhibitors/metabolism
MH  - Remission Induction
MH  - Signal Transduction/drug effects
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC3517479
EDAT- 2012/10/05 06:00
MHDA- 2013/05/25 06:00
PMCR- 2012/10/03
CRDT- 2012/10/05 06:00
PHST- 2012/06/08 00:00 [received]
PHST- 2012/10/02 00:00 [accepted]
PHST- 2012/10/05 06:00 [entrez]
PHST- 2012/10/05 06:00 [pubmed]
PHST- 2013/05/25 06:00 [medline]
PHST- 2012/10/03 00:00 [pmc-release]
AID - 1471-2407-12-449 [pii]
AID - 10.1186/1471-2407-12-449 [doi]
PST - epublish
SO  - BMC Cancer. 2012 Oct 3;12:449. doi: 10.1186/1471-2407-12-449.