Phase II study of Belinostat (PXD101), a histone deacetylase inhibitor, for second line therapy of advanced malignant pleural mesothelioma

• Type of Material: Article
• Authors: Suresh S Ramalingam, Emory University; Chandra P. Belani, Hershey Medical Center; Christopher Ruel, City of Hope Medical Center; Paul Frankel, City of Hope Medical Center; Barbara Gitlitz, University of Southern California Medical Center; Marianna Koczywas, City of Hope Medical Center; Igor Espinoza-Delgado, National Cancer Institute; David Gandara, University of California Davis Medical Center
• Language: English
• Date: 2009-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2008 by the International Association for the Study of Lung Cancer
• Final Published Version (URL): http://ovidsp.tx.ovid.com/sp-3.13.1a/ovidweb.cgi?QS2=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
• Title of Journal or Parent Work: Journal of Thoracic Oncology
• ISSN: 1556-0864
• Volume: 4
• Issue: 1
• Start Page: 97
• End Page: 101
• Grant/Funding Information: Supported by NCI NO1 CM-62209
• Keywords: belinostat; Mesothelioma; Histone deacetylase inhibition; PXD 101
• Research Categories: Health Sciences, Oncology; Health Sciences, General

Abstract

Background Belinostat (PXD 101) is a novel inhibitor of class I and II histone deacetylases. This class of compounds has demonstrated anti-cancer activity in malignant mesothelioma. We conducted a phase II study of belinostat in patients with relapsed malignant pleural mesothelioma. Methods Patients with advanced mesothelioma, progression with one prior chemotherapy regimen and ECOG PS 0-2 were eligible. Belinostat was administered at 1000 mg/m2 intravenously over 30 minutes on days 1–5 of every 3 week cycle. The primary endpoint was response rate. The Simon two-stage design was utilized. Disease assessments were performed every 2 cycles. Results Thirteen patients were enrolled. Baseline characteristics were: median age of 73 years; ECOG performance status 0 (n=4), 1 (8) and 2 (1). A median of 2 cycles of therapy were administered. Disease stabilization was seen in 2 patients. No objective responses were noted and the study did not meet criteria to proceed to the second stage of accrual. Median survival was 5 months with a median progression-free survival of 1 month. Salient toxicities included nausea, emesis, fatigue and constipation. One patient died as a consequence of cardiac arrhythmia which was deemed ‘possibly’ related to therapy. Conclusions Belinostat is not active as monotherapy against recurrent malignant pleural mesothelioma. Evaluation of combination strategies or alternate dosing schedules may be necessary for further development of this novel agent in mesothelioma.