A phase II randomized study of cisplatin-pemetrexed plus either enzastaurin or
placebo in chemonaive patients with advanced non-small cell lung cancer.
Author(s): Vansteenkiste J, Ramlau R, von Pawel J, San Antonio B, Eschbach C, Szczesna A,
Kennedy L, Visseren-Grul C, Chouaki N, Reck M.
Affiliation(s): Respiratory Oncology Unit (Pulmonology), University Hospital Gasthuisberg,
Leuven, Belgium. johan.vansteenkiste@uzleuven.be
Publication date & source: 2012, Oncology. , 82(1):25-9
OBJECTIVES: Enzastaurin is a serine/threonine kinase inhibitor that targets
protein kinase C and AKT pathways. Enzastaurin and pemetrexed demonstrated
synergy in preclinical studies. This trial was designed to evaluate the safety
and efficacy of first-line enzastaurin plus cisplatin-pemetrexed in advanced
non-small cell lung cancer (NSCLC).
METHODS: A safety lead-in phase (n = 13) of enzastaurin 125 or 250 mg twice daily
was added to cisplatin-pemetrexed. A subsequent randomized, placebo-controlled
phase II study (n = 22) of the combination was conducted to evaluate efficacy.
RESULTS: The combination was well tolerated and showed activity, with 7 (53.8%,
95% CI 26.7-80.9) confirmed partial responses and 2 stable diseases in 13 treated
patients in the lead-in phase. However, the study was terminated early based on
interim results from two phase II NSCLC studies of enzastaurin plus cytotoxic
chemotherapy, which indicated no efficacy improvement.
CONCLUSIONS: Enzastaurin and cisplatin-pemetrexed is tolerable with preliminary
activity in patients with advanced NSCLC, but because of a lack of efficacy
improvement in other phase II NSCLC studies, the study was terminated early.
|