title: A phase II study of oral enzastaurin in patients with metastatic breast cancer previously treated with an anthracycline and a taxane containing regimen.
abstract: OBJECTIVE
  Enzastaurin is a potent, serine-threonine kinase inhibitor which selectively targets PKCβ and PI3K/AKT signaling pathways to reduce cell proliferation, induce apoptosis, and inhibit angiogenesis. As PKCbeta and PI3K/AKT signaling are both involved in breast cancer pathogenesis, this phase II study evaluated the efficacy and toxicity of enzastaurin in previously treated patients with metastatic breast cancer (MBC).
  
  
  METHODS
  Eligible patients had histologically confirmed MBC with measurable disease, and must have received prior anthracycline and taxane chemotherapy, but not more than two prior regimens for MBC. Human epidermal growth factor 2 (HER2)-positive patients must have progressed on prior trastuzumab therapy. Enzastaurin, 1,125-mg loading dose on day 1 followed by 500 mg daily, was administered orally in 28-day cycles. Response was assessed every 2 cycles according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  
  
  RESULTS
  Twenty-one patients enrolled between November 2006 and September 2007. Fourteen (66.7%) patients completed at least two cycles of therapy. No patients developed Grade 3/4 hematologic toxicity. Grade 3 nonhematologic toxicity was rare (<5%) and most commonly attributed to MBC progression. There were no objective responses and no patients with stable disease for >/=6 months. Median progression-free survival was 1.68 months (95%CI: 1.02, 1.74).
  
  
  CONCLUSIONS
  Enzastaurin monotherapy was well tolerated, but demonstrated no activity in patients with heavily pretreated MBC.
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, 535 Barnhill Drive, Indianapolis, IN 46202, USA.
authors.forename: Lida
authors.initials: L
authors.lastname: Mina
authors.forename: Ian
authors.initials: I
authors.lastname: Krop
authors.forename: Robin T
authors.initials: RT
authors.lastname: Zon
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Isakoff
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Schneider
authors.forename: Menggang
authors.initials: M
authors.lastname: Yu
authors.forename: Cindy
authors.initials: C
authors.lastname: Johnson
authors.forename: LaTrice G
authors.initials: LG
authors.lastname: Vaughn
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Maria
authors.initials: M
authors.lastname: Hristova-Kazmierski
authors.forename: Oluwatoyin O
authors.initials: OO
authors.lastname: Shonukan
authors.forename: George W
authors.initials: GW
authors.lastname: Sledge
authors.forename: Kathy D
authors.initials: KD
authors.lastname: Miller
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D007211:Indoles; D043823:Taxoids; C080625:taxane; C504878:enzastaurin