From U Western Australia: A Phase II Study of Intermittent Sunitinib Malate as Second-Line Therapy in Progressive MalignantPleural Mesothelioma

http://www.ncbi.nlm.nih.gov/pubmed/22895142

J Thorac Oncol. 2012 Sep;7(9):1449-56.

A Phase II Study of Intermittent Sunitinib Malate as Second-Line Therapy in Progressive MalignantPleural Mesothelioma.

Nowak AK, Millward MJ, Creaney J, Francis RJ, Dick IM, Hasani A, van der Schaaf A, Segal A, Musk AW, Byrne MJ.

Source

*Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia; †School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; ‡National Centre for Asbestos Related Diseases, Western Australia, Perth, Australia; §Department of Nuclear Medicine, ║PathWest, ¶Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Australia; and #School of Population Health, University of Western Australia, Western Australia, Perth, Australia.

Abstract

INTRODUCTION:

: There is no accepted second-line therapy for patients with advanced malignant pleural mesothelioma (MPM), whose disease has progressed after first-line chemotherapy. The multitargeted tyrosine kinase inhibitor sunitinib malate targets several pathways overexpressed in mesothelioma. This phase II study assessed objective response to sunitinib and correlative biomarkers in patients with progressive pretreated MPM.

METHODS:

: Eligible patients had confirmed MPM, radiological progression after chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 1, and measurable disease. Patients received oral sunitinib 50 mg daily for 28 of every 42 days. The primary endpoint was objective radiological response. Patients without prior pleurodesis had fluorodeoxyglucose positron emission tomographic response assessed by total glycolytic volume criteria. Correlative biomarkers included serum mesothelin, vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, sVEGFR-2, sVEGFR-3, and s-kit.

RESULTS:

: Fifty-three patients received sunitinib between July 2006 and December 2009; 51 were assessable for response. Patients received a median of two cycles (range, 1-12); 40% required dose reduction. Fatigue was the most prominent toxicity. Six patients (12%) had a confirmed radiological partial response, 34 (65%) had stable disease, and 11 (22%) had progressive disease as best response. Six of 20 patients had a decrease in fluorodeoxyglucose positron emission tomographic total glycolytic volume of 15% or more. Median overall survival was 6.1 months, and median time to progression was 3.5 months. Correlative biomarkers did not predict treatment response.

CONCLUSIONS:

: Sunitinib has activity in a subset of patients with pretreated MPM. Consideration should be given to different treatment schedules and examination of other biomarkers for further study of sunitinib in MPM.