PMID- 20124186
OWN - NLM
STAT- MEDLINE
DCOM- 20100325
LR  - 20220330
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 28
IP  - 7
DP  - 2010 Mar 1
TI  - Phase III study of enzastaurin compared with lomustine in the treatment of 
      recurrent intracranial glioblastoma.
PG  - 1168-74
LID - 10.1200/JCO.2009.23.2595 [doi]
AB  - PURPOSE: This phase III open-label study compared the efficacy and safety of 
      enzastaurin versus lomustine in patients with recurrent glioblastoma (WHO grade 
      4). PATIENTS AND METHODS: Patients were randomly assigned 2:1 to receive 6-week 
      cycles of enzastaurin 500 mg/d (1,125-mg loading dose, day 1) or lomustine (100 
      to 130 mg/m(2), day 1). Assuming a 45% improvement in progression-free survival 
      (PFS), 397 patients were required to provide 80% power to achieve statistical 
      significance at a one-sided level of .025. RESULTS: Enrollment was terminated at 
      266 patients (enzastaurin, n = 174; lomustine, n = 92) after a planned interim 
      analysis for futility. Patient characteristics were balanced between arms. Median 
      PFS (1.5 v 1.6 months; hazard ratio [HR] = 1.28; 95% CI, 0.97 to 1.70), overall 
      survival (6.6 v 7.1 months; HR = 1.20; 95% CI, 0.88 to 1.65), and 6-month PFS 
      rate (P = .13) did not differ significantly between enzastaurin and lomustine, 
      respectively. Stable disease occurred in 38.5% and 35.9% of patients and 
      objective response occurred in 2.9% and 4.3% of patients, respectively. Time to 
      deterioration of physical and functional well-being and symptoms did not differ 
      between arms (HR = 1.12; P = .54). Four patients discontinued enzastaurin because 
      of drug-related serious adverse events (AEs). Eleven patients treated with 
      enzastaurin died on study (four because of AEs; one was drug-related). All four 
      deaths that occurred in patients receiving lomustine were disease-related. Grade 
      3 to 4 hematologic toxicities were significantly higher with lomustine (46 
      events) than with enzastaurin (one event; P < or = .001). CONCLUSION: Enzastaurin 
      was well tolerated and had a better hematologic toxicity profile but did not have 
      superior efficacy compared with lomustine in patients with recurrent 
      glioblastoma.
FAU - Wick, Wolfgang
AU  - Wick W
AD  - Department of Neurooncology, University of Heidelberg, Im Neuenheimer Feld, 400 
      D-69120 Heidelberg. wolfgang.wick@med.uni-heidelberg.de
FAU - Puduvalli, Vinay K
AU  - Puduvalli VK
FAU - Chamberlain, Marc C
AU  - Chamberlain MC
FAU - van den Bent, Martin J
AU  - van den Bent MJ
FAU - Carpentier, Antoine F
AU  - Carpentier AF
FAU - Cher, Lawrence M
AU  - Cher LM
FAU - Mason, Warren
AU  - Mason W
FAU - Weller, Michael
AU  - Weller M
FAU - Hong, Shengyan
AU  - Hong S
FAU - Musib, Luna
AU  - Musib L
FAU - Liepa, Astra M
AU  - Liepa AM
FAU - Thornton, Donald E
AU  - Thornton DE
FAU - Fine, Howard A
AU  - Fine HA
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20100201
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Indoles)
RN  - 7BRF0Z81KG (Lomustine)
RN  - UC96G28EQF (enzastaurin)
SB  - IM
CIN - J Clin Oncol. 28:1097. PMID: 20124164
MH  - Adult
MH  - Aged
MH  - Brain Neoplasms/*drug therapy/mortality
MH  - Female
MH  - Glioblastoma/*drug therapy/mortality
MH  - Humans
MH  - Indoles/adverse effects/pharmacokinetics/*therapeutic use
MH  - Lomustine/adverse effects/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy
PMC - PMC2834468
COIS- Authors' disclosures of potential conflicts of interest and author contributions 
      are found at the end of this article.
EDAT- 2010/02/04 06:00
MHDA- 2010/03/26 06:00
PMCR- 2011/03/01
CRDT- 2010/02/04 06:00
PHST- 2010/02/04 06:00 [entrez]
PHST- 2010/02/04 06:00 [pubmed]
PHST- 2010/03/26 06:00 [medline]
PHST- 2011/03/01 00:00 [pmc-release]
AID - JCO.2009.23.2595 [pii]
AID - 32595 [pii]
AID - 10.1200/JCO.2009.23.2595 [doi]
PST - ppublish
SO  - J Clin Oncol. 2010 Mar 1;28(7):1168-74. doi: 10.1200/JCO.2009.23.2595. Epub 2010 
      Feb 1.