Journal 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

Martins, Renato G, Jones, Dennie V, Arias-Pulido, Hugo, Cerilli, Lisa A, Lee, Sang-Joon, Wallace, Sarah G, Carr, Laurie L, Eaton, Keith D, Bauman, Julie E

2012

Overview

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

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Aged, 80 and over / Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Benzamides - administration & dosage / Benzamides - adverse effects / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - pathology / Chemotherapy / Clinical oncology / Clinical trials / Comorbidity / Dosage and administration / Dose-Response Relationship, Drug / Drug Administration Schedule / Drug therapy / Elderly / Fatigue - chemically induced / Female / Frail Elderly / Frailty / Health Promotion and Disease Prevention / Humans / Hypertension / Imatinib Mesylate / Interstitial fluid pressure / Lung - drug effects / Lung - metabolism / Lung - pathology / Lung cancer, Non-small cell / Lung cancer, Small cell / Lung Neoplasms - drug therapy / Lung Neoplasms - pathology / Male / Medical research / Medicine, Experimental / Medicine/Public Health / Neoplasm Staging / Neutropenia - chemically induced / Non-small cell lung cancer / Oncology / Paclitaxel / Paclitaxel - administration & dosage / Paclitaxel - adverse effects / Piperazines - administration & dosage / Piperazines - adverse effects / Platelet-derived growth factor / Proto-Oncogene Proteins c-sis - metabolism / Pyrimidines - administration & dosage / Pyrimidines - adverse effects / Receptors, Platelet-Derived Growth Factor - antagonists & inhibitors / Receptors, Platelet-Derived Growth Factor - metabolism / Remission Induction / Research Article / Signal Transduction - drug effects / Surgical Oncology / Survival Analysis / Treatment Outcome / Vulnerable elder survey