Fax: (313) 576-8628
Phase 2 randomized study of enzastaurin (LY317615) for lung cancer prevention in former smokers
Article first published online: 12 OCT 2012
Copyright © 2012 American Cancer Society
Volume 119, Issue 5, pages 1023–1032, 1 March 2013
How to Cite
Gray, J. E., Altiok, S., Alexandrow, M. G., Walsh, F. W., Chen, J., Schell, M. J., Tai, D. F. and Bepler, G. (2013), Phase 2 randomized study of enzastaurin (LY317615) for lung cancer prevention in former smokers. Cancer, 119: 1023–1032. doi: 10.1002/cncr.27836
- Issue published online: 19 FEB 2013
- Article first published online: 12 OCT 2012
- Manuscript Accepted: 9 AUG 2012
- Manuscript Revised: 2 AUG 2012
- Manuscript Received: 22 JUN 2012
- lung cancer;
- nonsmall cell lung cancer;
- protein kinase C-β;
- glycogen synthase kinase 3β;
- caspase 3;
Chemoprevention for lung cancer with nutraceutical or anti-inflammatory agents has had mixed clinical benefit. Novel targeted agents hold the promise of greater efficacy and selectivity. The authors of this report evaluated enzastaurin, a selective protein kinase C-β (PKC-β) inhibitor with antiproliferative and proapoptotic properties, in former smokers.
The primary objective of this study was to compare the average fraction of Ki-67–stained cells (the Ki-67 labeling index [LI]) in bronchial biopsy specimens that were collected before and after treatment. Participants were randomized (2:1) to receive either 6 months of daily oral enzastaurin (500 mg) or placebo. Stratification was based on morphology, history of lung cancer, and airway obstruction.
In pretrial investigations, the rationale for PKC-β inhibition and pathway interrogation was established in premalignant lesions and early stage lung cancer. In an intent-to-treat analysis, of 40 randomized participants, there was no significant difference in the pretreatment/post-treatment change in the Ki-67 LI between the enzastaurin group and the placebo group (P = .53). Six participants discontinued enzastaurin, including 4 participants who had adverse events, including abdominal distension, deep vein thrombosis, hyponatremia, and rash, and 2 participants who decided to discontinue. One participant in the placebo group was discontinued on the study because of noncompliance. Two participants had ≥1 serious adverse event (bradycardia, deep vein thrombosis, and hypotension).
To the authors' knowledge, this represents the first chemoprevention trial with a non-US Food and Drug Administration-approved, oral, small-molecule–targeted agent. Although the primary endpoint was not met, enzastaurin was tolerable for 6 months by 75% of participants, and there was a suggestion of response in a subset analysis that was restricted to those who had metaplastic or dysplastic lesions. Cancer 2013. © 2012 American Cancer Society.