Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer. Academic Article uri icon

Overview

abstract

  • UNLABELLED: Epigenetic alterations are strongly associated with the development of cancer. We conducted a phase I/II trial of combined epigenetic therapy with azacitidine and entinostat, inhibitors of DNA methylation and histone deacetylation, respectively, in extensively pretreated patients with recurrent metastatic non-small cell lung cancer. This therapy is well tolerated, and objective responses were observed, including a complete response and a partial response in a patient who remains alive and without disease progression approximately 2 years after completing protocol therapy. Median survival in the entire cohort was 6.4 months (95% CI 3.8-9.2), comparing favorably with existing therapeutic options. Demethylation of a set of 4 epigenetically silenced genes known to be associated with lung cancer was detectable in serial blood samples in these patients and was associated with improved progression-free (P = 0.034) and overall survival (P = 0.035). Four of 19 patients had major objective responses to subsequent anticancer therapies given immediately after epigenetic therapy. SIGNIFICANCE: This study demonstrates that combined epigenetic therapy with low-dose azacitidine and entinostat results in objective, durable responses in patients with solid tumors and defines a blood-based biomarker that correlates with clinical benefit.

publication date

  • November 9, 2011

Research

keywords

  • Antineoplastic Combined Chemotherapy Protocols
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Identity

PubMed Central ID

  • PMC3353724

Scopus Document Identifier

  • 84655163371

Digital Object Identifier (DOI)

  • 10.1158/2159-8290.CD-11-0214

PubMed ID

  • 22586682

Additional Document Info

volume

  • 1

issue

  • 7