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Open Access Research article

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

Julie E Bauman16*, Keith D Eaton2, Sarah G Wallace2, Laurie L Carr3, Sang-Joon Lee17, Dennie V Jones4, Hugo Arias-Pulido1, Lisa A Cerilli5 and Renato G Martins2

Author affiliations

1 Department of Internal Medicine, Divisions of Hematology/Oncology and Biostatistics, University of New Mexico Cancer Center, Albuquerque, New Mexico

2 Department of Internal Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA

3 Division of Medical Oncology, National Jewish Health, Denver, CO, USA

4 Department of Medicine, Division of Hematology/Oncology, University of Kentucky, Lexington, KY, USA

5 Department of Pathology, University of Michigan, Ann Arbor, MI, USA

6 University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, 5th floor, Pittsburgh, 15232, PA, USA

7 Celltrion, Inc. Incheon, Korea

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Citation and License

BMC Cancer 2012, 12:449  doi:10.1186/1471-2407-12-449

Published: 3 October 2012

Abstract

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

Keywords:
Non-small cell lung cancer; Imatinib mesylate; Paclitaxel; Elderly; Interstitial fluid pressure; Platelet-derived growth factor; Frailty; Vulnerable elder survey