Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer

Rosalyn A. Juergens, John Wrangle, Frank P. Vendetti, Sara C. Murphy, Ming Zhao, Barbara Coleman, Rosa Sebree, Kristen Rodgers, Craig M. Hooker, Noreli Franco, Beverly Lee, Salina Tsai, Igor Espinoza Delgado, Michelle A. Rudek, Steven A. Belinsky, James G. Herman, Stephen B. Baylin, Malcolm V. Brock, Charles M. Rudin

Research output: Contribution to journalArticlepeer-review

Abstract

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 bloodbased biomarker that correlates with clinical benefit.

Original languageEnglish (US)
Pages (from-to)598-607
Number of pages10
JournalCancer discovery
Volume1
Issue number7
DOIs
StatePublished - Dec 2011

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer'. Together they form a unique fingerprint.

Cite this