A Gynecologic Oncology Group phase II trial of the protein kinase C-beta inhibitor, enzastaurin and evaluation of markers with potential predictive and prognostic value in persistent or recurrent epithelial ovarian and primary peritoneal malignancies

Gynecologic Oncology

Volumn 121, Issue 3, 2011, Pages 455-461

  Usha, Lydia ^a,j   Sill, Michael W ^b,c   Darcy, Kathleen M ^b   Benbrook, Doris M ^d   Hurteau, Jean A ^e   Michelin, David P ^f   Mannel, Robert S ^d   Hanjani, Parviz ^g   De Geest, Koen ^h   Godwin, Andrew K ⁱ  

^a RUSH MEDICAL COLLEGE   (United States)

^b ROSWELL PARK CANCER INSTITUTE   (United States)

^c UNIVERSITY AT BUFFALO   (United States)

^d UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

^e NORTHSHORE UNIVERSITY HEALTHSYSTEM   (United States)

^f MUNSON MEDICAL CENTER   (United States)

^g ABINGTON MEMORIAL HOSPITAL   (United States)

^h UNIVERSITY OF IOWA HOSPITALS AND CLINICS   (United States)

ⁱ UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

^j RUSH UNIVERSITY MEDICAL CENTER   (United States)

more..

Author keywords

AKT2; Enzastaurin; Ovarian cancer; PIK3CA; PKC ; PTEN

Indexed keywords

CARBOPLATIN; DOXORUBICIN; ENZASTAURIN; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PIK3CA PROTEIN; PROTEIN KINASE B BETA; PROTEIN KINASE C BETA; PROTEIN P53; TUMOR MARKER; UNCLASSIFIED DRUG;

ADULT; AGED; ANEMIA; ARTICLE; BLEEDING; CANCER GROWTH; CANCER PAIN; CANCER SURVIVAL; CARDIOVASCULAR SYMPTOM; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE FREE SURVIVAL; DIZZINESS; DNA EXTRACTION; DRUG EFFICACY; DRUG SAFETY; DRUG SUBSTITUTION; DRUG WITHDRAWAL; DYSPNEA; FEMALE; GASTROINTESTINAL SYMPTOM; HUMAN; HUMAN CELL; HYPERKALEMIA; INFECTION; LEUKOPENIA; LUNG DISEASE; LYMPHATIC SYSTEM DISEASE; METABOLIC DISORDER; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROLOGIC DISEASE; NEUTROPENIA; OVARY ADENOCARCINOMA; OVARY CANCER; PERITONEUM CANCER; PHASE 2 CLINICAL TRIAL; POLYMERASE CHAIN REACTION; PREDICTIVE VALUE; PRIORITY JOURNAL; PROTEIN ANALYSIS; SKIN DISEASE; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT RESPONSE; UROGENITAL TRACT DISEASE; VOMITING;

ADULT; AGED; FEMALE; GENES, P53; HUMANS; INDOLES; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; NEOPLASMS, GLANDULAR AND EPITHELIAL; OVARIAN NEOPLASMS; PERITONEAL NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE C; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; PTEN PHOSPHOHYDROLASE; TUMOR MARKERS, BIOLOGICAL; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 79957463319     PISSN: 00908258     EISSN: 10956859     Source Type: Journal    
DOI: 10.1016/j.ygyno.2011.02.013     Document Type: Article

References (52)

1. A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, and M.J. Thun Cancer statistics, 2009 CA Cancer J Clin 59 2009 225 249
2. R.F. Ozols Treatment goals in ovarian cancer Int J Gynecol Cancer 15 Suppl 1 2005 3 11 (Pubitemid 40696471)
3. Y.B. Chen, and A.S. LaCasce Enzastaurin Expert Opin Investig Drugs 17 2008 939 944
4. S. Ma, and S.T. Rosen Enzastaurin Curr Opin Oncol 19 2007 590 595 (Pubitemid 47508866)
5. L.J. Green, P. Marder, C. Ray, C.A. Cook, S. Jaken, and L.C. Musib Development and validation of a drug activity biomarker that shows target inhibition in cancer patients receiving enzastaurin, a novel protein kinase C-beta inhibitor Clin Cancer Res 12 2006 3408 3415
6. A.P. Fields, and N.R. Murray Protein kinase C isozymes as therapeutic targets for treatment of human cancers Adv Enzyme Regul 48 2008 166 178
7. A. Gonelli, C. Mischiati, R. Guerrini, R. Voltan, S. Salvadori, and G. Zauli Perspectives of protein kinase C (PKC) inhibitors as anti-cancer agents Mini Rev Med Chem 9 2009 498 509
8. Y. Gokmen-Polar, N.R. Murray, M.A. Velasco, Z. Gatalica, and A.P. Fields Elevated protein kinase C betaII is an early promotive event in colon carcinogenesis Cancer Res 61 2001 1375 1381 (Pubitemid 34292559)
9. S.E. Aeder, P.M. Martin, J.W. Soh, and I.M. Hussaini PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways Oncogene 23 2004 9062 9069 (Pubitemid 40013073)
10. E. Tokunaga, E. Oki, A. Egashira, N. Sadanaga, M. Morita, and Y. Kakeji Deregulation of the Akt pathway in human cancer Curr Cancer Drug Targets 8 2008 27 36 (Pubitemid 351237907)
11. I. Vivanco, and C.L. Sawyers The phosphatidylinositol 3-Kinase AKT pathway in human cancer Nat Rev Cancer 2 2002 489 501 (Pubitemid 37328931)
12. M.A. Carducci, L. Musib, M.S. Kies, R. Pili, M. Truong, and J.R. Brahmer Phase I dose escalation and pharmacokinetic study of enzastaurin, an oral protein kinase C beta inhibitor, in patients with advanced cancer J Clin Oncol 24 2006 4092 4099 (Pubitemid 46622284)
13. J.R. Graff, A.M. McNulty, K.R. Hanna, B.W. Konicek, R.L. Lynch, and S.N. Bailey The protein kinase Cbeta-selective inhibitor, Enzastaurin (LY317615.HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts Cancer Res 65 2005 7462 7469 (Pubitemid 41161281)
14. K.A. Keyes, L. Mann, M. Sherman, E. Galbreath, L. Schirtzinger, and D. Ballard LY317615 decreases plasma VEGF levels in human tumor xenograft-bearing mice Cancer Chemother Pharmacol 53 2004 133 140 (Pubitemid 38186992)
15. A.D. Santin, P.L. Hermonat, A. Ravaggi, M.J. Cannon, S. Pecorelli, and G.P. Parham Secretion of vascular endothelial growth factor in ovarian cancer Eur J Gynaecol Oncol 20 1999 177 181 (Pubitemid 29286483)
16. R.A. Burger, M.W. Sill, B.J. Monk, B.E. Greer, and J.I. Sorosky Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study J Clin Oncol 25 2007 5165 5171 (Pubitemid 350237599)
17. D.A. Levine, F. Bogomolniy, C.J. Yee, A. Lash, R.R. Barakat, and P.I. Borgen Frequent mutation of the PIK3CA gene in ovarian and breast cancers Clin Cancer Res 11 2005 2875 2878 (Pubitemid 40525186)
18. J.Q. Cheng, A.K. Godwin, A. Bellacosa, T. Taguchi, T.F. Franke, and T.C. Hamilton AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas Proc Natl Acad Sci U S A 89 1992 9267 9271
19. A. Bellacosa, D. de Feo, A.K. Godwin, D.W. Bell, J.Q. Cheng, and D.A. Altomare Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas Int J Cancer 64 1995 280 285
20. M. Saito, A. Okamoto, T. Kohno, S. Takakura, H. Shinozaki, and S. Isonishi Allelic imbalance and mutations of the PTEN gene in ovarian cancer Int J Cancer 85 2000 160 165 (Pubitemid 30023061)
21. I. Sansal, and W.R. Sellers The biology and clinical relevance of the PTEN tumor suppressor pathway J Clin Oncol 22 2004 2954 2963 (Pubitemid 41079915)
22. Q.J. Lu, X.D. Zhao, J.Y. Song, X.H. Li, Y. Ma, and H. Meng Research on the mechanisms of PTEN gene inactivation in ovarian cancer Zhonghua Bing Li Xue Za Zhi 34 2005 266 269
23. M. Cully, H. You, A.J. Levine, and T.W. Mak Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis Nat Rev Cancer 6 2006 184 192 (Pubitemid 43292562)
24. X. Yang, M. Fraser, U.M. Moll, A. Basak, and B.K. Tsang Akt-mediated cisplatin resistance in ovarian cancer: modulation of p53 action on caspase-dependent mitochondrial death pathway Cancer Res 66 2006 3126 3136
25. P. Therasse, S.G. Arbuck, E.A. Eisenhauer, J. Wanders, R.S. Kaplan, and L. Rubinstein New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada J Natl Cancer Inst 92 2000 205 216
26. M.W. Sill, and G. Yothers A method for utilizing bivariate efficacy outcome measures to screen agents for activity in 2-stage phase II clinical trials Technical Report 06-08, Department of Biostatistics, University at Buffalo 2006
27. M. Markman, J.A. Blessing, K. DeGeest, M. Morgan, K.Y. Look, and T.J. Herzog Lack of efficacy of 24-h infusional topotecan in platinum-refractory ovarian cancer: a Gynecologic Oncology Group trial Gynecol Oncol 75 1999 444 446
28. M. Markman, J.A. Blessing, D. Moore, H. Ball, and S.S. Lentz Altretamine (hexamethylmelamine) in platinum-resistant and platinum-refractory ovarian cancer: a Gynecologic Oncology Group phase II trial Gynecol Oncol 69 1998 226 229 (Pubitemid 28289964)
29. F.M. Muggia, J.A. Blessing, H.D. Homesley, and J. Sorosky Tomudex (ZD1694, NSC 639186) in platinum-pretreated recurrent epithelial ovarian cancer: a phase II study by the Gynecologic Oncology Group Cancer Chemother Pharmacol 42 1998 68 70 (Pubitemid 28224993)
30. A. Manetta, J.A. Blessing, and J.A. Hurteau Evaluation of cisplatin and cyclosporin A in recurrent platinum-resistant ovarian cancer: a phase II study of the gynecologic oncology group Gynecol Oncol 68 1998 45 46 (Pubitemid 28109822)
31. M. Markman, J.A. Blessing, R.D. Alvarez, P. Hanjani, S. Waggoner, and K. Hall Phase II evaluation of 24-h continuous infusion topotecan in recurrent, potentially platinum-sensitive ovarian cancer: a Gynecologic Oncology Group study Gynecol Oncol 77 2000 112 115 (Pubitemid 30217313)
32. S.C. Plaxe, J.A. Blessing, M.A. Morgan, J. Carlson, and Gynecologic Oncology Group Phase II trial of pyrazoloacridine in recurrent platinum-resistant ovarian cancer: a Gynecologic Oncology Group study Am J Clin Oncol 25 2002 45 47 (Pubitemid 34131028)
33. P.M. Fracasso, J.A. Blessing, M.A. Morgan, A.K. Sood, and J.S. Hoffman Phase II study of oxaliplatin in platinum-resistant and refractory ovarian cancer: a gynecologic group study J Clin Oncol 21 2003 2856 2859 (Pubitemid 46621833)
34. P.M. Fracasso, M.F. Brady, D.H. Moore, J.L. Walker, P.G. Rose, and L. Letvak Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: a gynecologic oncology group study J Clin Oncol 19 2001 2975 2982 (Pubitemid 32565435)
35. M.A. Hoffman, J.A. Blessing, S.S. Lentz, and Gynecologic Oncology Group Study A phase II trial of dolastatin-10 in recurrent platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study Gynecol Oncol 89 2003 95 98 (Pubitemid 36403653)
36. M.A. Hoffman, J.A. Blessing, and M. Morgan Phase II trial of CI-958 in recurrent platinum-refractory ovarian carcinoma. A Gynecologic Oncology Group Study Gynecol Oncol 79 2000 463 465
37. M.A. Hoffman, J.A. Blessing, and E.R. Nuñez A phase II trial of CI-958 in recurrent platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study Gynecol Oncol 81 2001 433 435 (Pubitemid 32494658)
38. D.R. Cox Regression models and life tables J R Stat Soc B 34 1972 187 220
39. M.G. Kendall The treatment of ties in rank problems Biometrika 33 1945 239 251
40. C. Spearman The proof and measurement of association between two things Am J Psychol 15 1904 72 101
41. R.A. Fisher Statistical methods for research workers 1934 1970 Oliver and Boyd Edinburgh
42. M. Hollander, and D.A. Wolfe Nonparametric statistical methods 1973 John Wiley & Sons New York
43. Y. Baohua, Z. Xiaoyan, Z. Tiecheng, Q. Tao, and S. Daren Mutations of the PIK3CA gene in diffuse large B cell lymphoma Diagn Mol Pathol 17 2008 159 165
44. T.N. Kreisl, S. Kotliarova, J.A. Butman, P.S. Albert, L. Kim, and L. Musib A phase I/II trial of enzastaurin in patients with recurrent high-grade gliomas Neuro Oncol 12 2010 181 189
45. Y. Oh, R.S. Herbst, H. Burris, A. Cleverly, L. Musib, and M. Lahn Enzastaurin, an oral serine/threonine kinase inhibitor, as second- or third-line therapy of non-small-cell lung cancer J Clin Oncol 26 2008 1135 1141
46. F. Morschhauser, J.F. Seymour, H.C. Kluin-Nelemans, A. Grigg, M. Wolf, and M. Pfreundschuh A phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory mantle cell lymphoma Ann Oncol 19 2008 247 253 (Pubitemid 351209293)
47. R. Advani, P. Peethambaram, B.L. Lum, G.A. Fisher, L. Hartmann, and H.J. Long A phase II trial of aprinocarsen, an antisense oligonucleotide inhibitor of protein kinase C alpha, administered as a 21-day infusion to patients with advanced ovarian carcinoma Cancer 100 2004 321 326 (Pubitemid 38063641)
48. D.K. Armstrong, J.A. Blessing, K.Y. Look, R. Schilder, and E.R. Nunez A randomized phase II evaluation of bryostatin-1 (NSC #339555) in recurrent or persistent platinum-sensitive ovarian cancer: a Gynecologic Oncology Group Study Invest New Drugs 21 2003 373 377 (Pubitemid 37486339)
49. A.R. Clamp, F.H. Blackhall, P. Vasey, M. Soukop, R. Coleman, and G. Halbert A phase II trial of bryostatin-1 administered by weekly 24-hour infusion in recurrent epithelial ovarian carcinoma Br J Cancer 89 2003 1152 1154 (Pubitemid 37363393)
50. D.K. Armstrong, S. Ermisch, C. Collins, S. Nicol, T. Wang, and Z. Zhang A phase I study of enzastaurin and bevacizumab in patients with advanced cancer: response and clinical benefit in ovarian and other gynecologic cancers Gynecol Oncol 116 2010 S16
51. B. Glimelius, M. Lahn, S. Gawande, A. Cleverly, C. Darstein, and L. Musib A window of opportunity phase II study of enzastaurin in chemonaive patients with asymptomatic metastatic colorectal cancer Ann Oncol 21 2010 1020 1026
52. D.A. Richards, P.R. Kuefler, C. Becerra, L.S. Wilfong, R.H. Gersh, and K.A. Boehm Gemcitabine plus enzastaurin or single-agent gemcitabine in locally advanced or metastatic pancreatic cancer: results of a Phase II, randomized, noncomparative study Invest New Drugs 29 2011 144 153 [Epub 2009 Aug 28]