title: A phase II randomized study of cisplatin-pemetrexed plus either enzastaurin or placebo in chemonaive patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Respiratory Oncology Unit (Pulmonology), University Hospital Gasthuisberg, Leuven, Belgium. johan.vansteenkiste@uzleuven.be
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.forename: Rodryg
authors.initials: R
authors.lastname: Ramlau
authors.forename: Joachim
authors.initials: J
authors.lastname: von Pawel
authors.forename: Belen
authors.initials: B
authors.lastname: San Antonio
authors.forename: Corinna
authors.initials: C
authors.lastname: Eschbach
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szczesna
authors.forename: Liam
authors.initials: L
authors.lastname: Kennedy
authors.forename: Carla
authors.initials: C
authors.lastname: Visseren-Grul
authors.forename: Nadia
authors.initials: N
authors.lastname: Chouaki
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D010919:Placebos
chemical_list: D005971:Glutamates; D007211:Indoles; D010919:Placebos; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin; C504878:enzastaurin