A phase II trial of enzastaurin (LY317615) in combination with bevacizumab in adults with recurrent malignant gliomas

被引:31
|
作者
Odia, Yazmin [1 ]
Iwamoto, Fabio M. [1 ]
Moustakas, Argirios [2 ]
Fraum, Tyler J. [3 ]
Salgado, Carlos A. [4 ]
Li, Aiguo [5 ]
Kreisl, Teri N. [1 ]
Sul, Joohee [6 ]
Butman, John A. [7 ]
Fine, Howard A. [8 ]
机构
[1] Columbia Univ Coll Phys & Surg, Neurooncol Div, Neurol Inst New York, 710 West 168th St,9th Floor,NI 9-017, New York, NY 10032 USA
[2] Univ Vermont, Med Ctr, 89 South Williams St, Burlington, VT 05401 USA
[3] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Campus Box 8131,510 S Kingshighway Blvd, St Louis, MO 63110 USA
[4] Univ Maryland, Sch Med, 655 West Baltimore St, Baltimore, MD 21201 USA
[5] NCI, Ctr Canc Res, Bldg 37,Room 1142, Bethesda, MD USA
[6] Fed Drug Adm, 10903 New Hampshire Ave,Bldg WO22 Rm 2331, Silver Spring, MD 20993 USA
[7] NIH, Ctr Clin, Dept Radiol, Bldg 10,Clinical Ctr 10 Ctr Dr,MSC 1074, Bethesda, MD 20892 USA
[8] New York Presbyterian Hospital, Weill Cornell Med Ctr, Brain Tumor Ctr, Div Neurooncol, 1305 York Ave,9th Floor, New York, NY 10021 USA
关键词
Enzastaurin; Bevacizumab; Trial; Glioma; Glioblastoma; PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; RECURSIVE PARTITIONING ANALYSIS; SINGLE-AGENT BEVACIZUMAB; GLIOBLASTOMA-MULTIFORME; PLUS IRINOTECAN; CELL-GROWTH; IN-VIVO; RADIOTHERAPY; TEMOZOLOMIDE;
D O I
10.1007/s11060-015-2020-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We evaluated the efficacy of combination enzastaurin (LY317615) and bevacizumab for recurrent malignant gliomas and explored serologic correlates. We enrolled 81 patients with glioblastomas (GBM, n = 40) and anaplastic gliomas (AG, n = 41). Patients received enzastaurin as a loading dose of 1125 mg, followed by 500 or 875 mg daily for patients on non-enzyme-inducing or enzyme-inducing antiepileptics, respectively. Patients received bevacizumab 10 mg/kg intravenously biweekly. Clinical evaluations were repeated every 4 weeks. Magnetic resonance imaging was obtained at baseline and every 8 weeks from treatment onset. Phosphorylated glycogen synthase kinase (GSK)-3 levels from peripheral blood mononuclear cells (PBMCs) were checked with each MRI. Median overall survival was 7.5 and 12.4 months for glioblastomas and anaplastic glioma cohorts, with median progression-free survivals of 2.0 and 4.4 months, respectively. Of GBM patients, 3/40 (7.5 %) were not evaluable, while 8/37 (22 %) had partial or complete response and 20/37 (54 %) had stable disease for 2+ months. Of the 39 evaluable AG patients, 18 (46 %) had an objective response, and 16 (41 %) had stable disease for 2+ months. The most common grade 3+ toxicities were lymphopenia (15 %), hypophosphatemia (8.8 %) and thrombotic events (7.5 %). Two (2.5 %) GBM patients died suddenly; another death (1.3 %) occurred from intractable seizures. Phosphorylated GSK-3 levels from PBMCs did not correlate with treatment response. A minimally important improvement in health-related quality of life was self-reported in 7-9/24 (29.2-37.5 %). Early response based on Levin criteria was significantly associated with significantly longer progression free survival for glioblastomas. Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy.
引用
收藏
页码:127 / 135
页数:9
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