title: Randomized, phase II trial of pemetrexed and carboplatin with or without enzastaurin versus docetaxel and carboplatin as first-line treatment of patients with stage IIIB/IV non-small cell lung cancer.
abstract: BACKGROUND
  Enzastaurin is an oral serine/threonine kinase inhibitor that targets protein kinase C-beta (PKC-β) and the phosphatidylinositol-3-kinase/AKT pathway. This trial assessed pemetrexed-carboplatin ± enzastaurin to docetaxel-carboplatin in advanced non-small cell lung cancer.
  
  
  METHODS
  Patients with stage IIIB (with pleural effusion) or IV non-small cell lung cancer and performance status 0 or 1 were randomized to one of the three arms: (A) pemetrexed 500 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to 6 cycles with a loading dose of enzastaurin 1125 or 1200 mg followed by 500 mg daily until disease progression, (B) the same regimen of pemetrexed-carboplatin without enzastaurin, or (C) docetaxel 75 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to six cycles. The primary end point was time to disease progression (TTP).
  
  
  RESULTS
  Between March 2006 and May 2008, 218 patients were randomized. Median TTP was 4.6 months for pemetrexed-carboplatin-enzastaurin, 6.0 months for pemetrexed-carboplatin, and 4.1 months for docetaxel-carboplatin (differences not significant). Median survival was 7.2 months for pemetrexed-carboplatin-enzastaurin, 12.7 months for pemetrexed-carboplatin, and 9.2 months for docetaxel-carboplatin (log-rank p = 0.05). Compared with the other arms, docetaxel-carboplatin was associated with lower rates of grade 3 thrombocytopenia and anemia but a higher rate of grade 3 or 4 febrile neutropenia.
  
  
  CONCLUSIONS
  There was no difference in TTP between the three arms, but survival was longer with pemetrexed-carboplatin compared with docetaxel-carboplatin. Enzastaurin did not add to the activity of pemetrexed-carboplatin.
authors.affiliation: Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7305, USA. socinski@med.unc.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Robert N
authors.initials: RN
authors.lastname: Raju
authors.forename: Thomas
authors.initials: T
authors.lastname: Stinchcombe
authors.forename: Darren M
authors.initials: DM
authors.lastname: Kocs
authors.forename: Linda S
authors.initials: LS
authors.lastname: Couch
authors.forename: David
authors.initials: D
authors.lastname: Barrera
authors.forename: Steven R
authors.initials: SR
authors.lastname: Rousey
authors.forename: Janak K
authors.initials: JK
authors.lastname: Choksi
authors.forename: Robert
authors.initials: R
authors.lastname: Jotte
authors.forename: Debra A
authors.initials: DA
authors.lastname: Patt
authors.forename: Phillip O
authors.initials: PO
authors.lastname: Periman
authors.forename: Howard R
authors.initials: HR
authors.lastname: Schlossberg
authors.forename: Charles H
authors.initials: CH
authors.lastname: Weissman
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.forename: Lina
authors.initials: L
authors.lastname: Asmar
authors.forename: Sharon
authors.initials: S
authors.lastname: Pritchard
authors.forename: Jane
authors.initials: J
authors.lastname: Bromund
authors.forename: Guangbin
authors.initials: G
authors.lastname: Peng
authors.forename: Joseph
authors.initials: J
authors.lastname: Treat
authors.forename: Coleman K
authors.initials: CK
authors.lastname: Obasaju
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000523:psychology; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000523:psychology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011788:Quality of Life
chemical_list: D005971:Glutamates; D007211:Indoles; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin; C504878:enzastaurin