Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: A Gynecologic Oncology Group study

Gynecologic Oncology

Volumn 123, Issue 1, 2011, Pages 19-26

  Behbakht, Kian ^a   Sill, Michael W ^b,c   Darcy, Kathleen M ^b   Rubin, Stephen C ^d   Mannel, Robert S ^e   Waggoner, Steven ^f   Schilder, Russell J ^g   Cai, Kathy Q ^g   Godwin, Andrew K ^h   Alpaugh, R Katherine ^h  

^a UNIVERSITY OF COLORADO   (United States)

^b ROSWELL PARK CANCER INSTITUTE   (United States)

^c UNIVERSITY AT BUFFALO   (United States)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

^e UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER   (United States)

^f UNIVERSITY HOSPITALS OF CLEVELAND   (United States)

^g UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

^h FOX CHASE CANCER CENTER   (United States)

Author keywords

AKT PI3K pathway; Circulating tumor cells; mTOR inhibitor; Ovarian clinical trial

Indexed keywords

BIOLOGICAL MARKER; CYCLIN D1; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; PROTEIN KINASE B; TAU PROTEIN; TEMSIROLIMUS; TUMOR MARKER;

ADULT; AGED; ANEMIA; ARTICLE; BLEEDING; BLOOD CLOTTING DISORDER; CANCER RECURRENCE; CIRCULATING TUMOR CELL; CONTROLLED STUDY; DIARRHEA; DISEASE ASSOCIATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; ELECTROLYTE DISTURBANCE; FEMALE; GASTROINTESTINAL SYMPTOM; HEART DISEASE; HUMAN; HYPERGLYCEMIA; HYPERLIPIDEMIA; IMMUNOHISTOCHEMISTRY; INFECTION; KIDNEY DISEASE; LEUKOPENIA; LUNG DISEASE; MAJOR CLINICAL STUDY; METABOLIC DISORDER; MUSCULOSKELETAL DISEASE; NAUSEA; NEUTROPENIA; OVARY CANCER; PAIN; PERIPHERAL NEUROPATHY; PERITONEUM CANCER; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; SEXUAL DYSFUNCTION; SIDE EFFECT; SKIN DISEASE; SURVIVAL TIME; THROMBOCYTOPENIA; TREATMENT OUTCOME; TREATMENT RESPONSE; TUMOR GROWTH; UROGENITAL TRACT DISEASE; VASCULAR DISEASE; VISUAL DISORDER; VOMITING;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; CYCLIN D1; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; MIDDLE AGED; NEOPLASMS, GLANDULAR AND EPITHELIAL; NEOPLASTIC CELLS, CIRCULATING; OVARIAN NEOPLASMS; PERITONEAL NEOPLASMS; PROTO-ONCOGENE PROTEINS C-AKT; SIROLIMUS; TOR SERINE-THREONINE KINASES; TUMOR MARKERS, BIOLOGICAL; YOUNG ADULT;

EID: 80052588957     PISSN: 00908258     EISSN: 10956859     Source Type: Journal    
DOI: 10.1016/j.ygyno.2011.06.022     Document Type: Article

References (79)

1. A. Jemal, R. Siegel, and E. Ward Cancer statistics, 2008 CA Cancer J Clin 58 2008 71 96 (Pubitemid 351521864)
2. A.E. Guppy, P.D. Nathan, and G.J. Rustin Epithelial ovarian cancer: a review of current management Clin Oncol (R Coll Radiol) 17 2005 399-41
3. R.F. Ozols Systemic therapy for ovarian cancer: current status and new treatments Semin Oncol 33 2006 S3 S11
4. R.J. Shaw, and L.C. Cantley Ras, PI(3)K and mTOR signalling controls tumour cell growth Nature 441 2006 424 430 (Pubitemid 44050136)
5. M. Sun, G. Wang, and J.E. Paciga AKT1/PKBalpha kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells Am J Pathol 159 2001 431 437 (Pubitemid 32751073)
6. D.A. Altomare, S. Tanno, and A. De Rienzo Frequent activation of AKT2 kinase in human pancreatic carcinomas J Cell Biochem 87 2002 470 476
7. D.A. Altomare, H.Q. Wang, and K.L. Skele AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth Oncogene 23 2004 5853 5857 (Pubitemid 39093031)
8. J. Brognard, A.S. Clark, and Y. Ni Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation Cancer Res 61 2001 3986 3997 (Pubitemid 32720961)
9. T. Schmelzle, and M.N. Hall TOR, a central controller of cell growth Cell 103 2000 253 262
10. K. Yu, L. Toral-Barza, and C. Discafani mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer Endocr Relat Cancer 8 2001 249 258 (Pubitemid 32947647)
11. M.B. Atkins, M. Hidalgo, and W.M. Stadler Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma J Clin Oncol 22 2004 909 918 (Pubitemid 41103603)
12. J.E. Dancey Clinical development of mammalian target of rapamycin inhibitors Hematol Oncol Clin North Am 16 2002 1101 1114 (Pubitemid 35462916)
13. S. Mabuchi, D.A. Altomare, and P.I. Poulikakos The mTOR inhibitor RAD001 inhibits the proliferation of p53-deficient human ovarian cancer cells, enhances the efficacy of cisplatin in vitro, and prolongs survival in an in vivo ovarian cancer model Clin Cancer Res 13 2007 4261 4270 (Pubitemid 47105991)
14. S. Mabuchi, C. Kawase, and D.A. Altomare mTOR is a promising target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary Clin Cancer Res 15 2009 5404 5413
15. R. Yuan, A. Kay, and W.J. Berg Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy J Hematol Oncol 2 2009 45
16. J. Alexandre, E. Raymond, and J.P. Armand Rapamycin and CCI-779 Bull Cancer 86 1999 808 811
17. M. Hidalgo, J.C. Buckner, and C. Erlichman A phase I and pharmacokinetic study of temsirolimus (CCI-779) administered intravenously daily for 5 days every 2 weeks to patients with advanced cancer Clin Cancer Res 12 2006 5755 5763 (Pubitemid 44629606)
18. E. Raymond, J. Alexandre, and S. Faivre Safety and pharmacokinetics of escalated doses of weekly intravenous infusion of CCI-779, a novel mTOR inhibitor, in patients with cancer J Clin Oncol 22 2004 2336 2347 (Pubitemid 41115390)
19. M. Balic, N. Dandachi, and G. Hofmann Comparison of two methods for enumerating circulating tumor cells in carcinoma patients Cytometry B Clin Cytom 68 2005 25 30 (Pubitemid 41566360)
20. M. Cristofanilli, G.T. Budd, and M.J. Ellis Circulating tumor cells, disease progression, and survival in metastatic breast cancer N Engl J Med 351 2004 781 791 (Pubitemid 39095313)
21. S. Dawood, and M. Cristofanilli Integrating circulating tumor cell assays into the management of breast cancer Curr Treat Options Oncol 8 2007 89 95
22. S. Dawood, K. Broglio, and V. Valero Circulating tumor cells in metastatic breast cancer: from prognostic stratification to modification of the staging system? Cancer 113 2008 2422 2430
23. O.B. Goodman Jr., L.M. Fink, and J.T. Symanowski Circulating tumor cells in patients with castration-resistant prostate cancer baseline values and correlation with prognostic factors Cancer Epidemiol Biomarkers Prev 18 2009 1904 1913
24. D.C. Danila, G. Heller, and G.A. Gignac Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer Clin Cancer Res 13 2007 7053 7058 (Pubitemid 350276887)
25. S.J. Cohen, R.K. Alpaugh, and S. Gross Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer Clin Colorectal Cancer 6 2006 125 132 (Pubitemid 44445747)
26. S.J. Cohen, C.J. Punt, and N. Iannotti Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer J Clin Oncol 26 2008 3213 3221
27. S.J. Cohen, C.J. Punt, and N. Iannotti Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer Ann Oncol 20 2009 1223 1229
28. W. He, H. Wang, and L.C. Hartmann In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry Proc Natl Acad Sci USA 104 2007 11760 11765 (Pubitemid 47175086)
29. W. He, S.A. Kularatne, and K.R. Kalli Quantitation of circulating tumor cells in blood samples from ovarian and prostate cancer patients using tumor-specific fluorescent ligands Int J Cancer 123 2008 1968 1973
30. D.R. Shaffer, M.A. Leversha, and D.C. Danila Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer Clin Cancer Res 13 2007 2023 2029 (Pubitemid 46649868)
31. E.C. de Haas, A. di Pietro, and K.L. Simpson Clinical evaluation of M30 and M65 ELISA cell death assays as circulating biomarkers in a drug-sensitive tumor, testicular cancer Neoplasia 10 2008 1041 1048
32. M. Kagan, D. Howard, and T. Bendele A sample preparation and analysis system for identification of circulating tumor cells J Clin Ligand Assay 25 2002 104 110 (Pubitemid 34984736)
33. 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 State University of New York at Buffalo Department of Biostatistics Technical Report 2006-2008 2008
34. 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)
35. M. Markman, J.A. Blessing, and D. Moore 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)
36. S.C. Plaxe, J.A. Blessing, and M.A. Morgan 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)
37. P.M. Fracasso, M.F. Brady, and D.H. Moore 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)
38. 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
39. M. Markman, J.A. Blessing, and K. DeGeest Lack of efficacy of 24-h infusional topotecan in platinum-refractory ovarian cancer: a Gynecologic Oncology Group trial Gynecol Oncol 75 1999 444 446
40. P.M. Fracasso, J.A. Blessing, and M.A. Morgan 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)
41. F.M. Muggia, J.A. Blessing, and H.D. Homesley 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)
42. M.A. Hoffman, J.A. Blessing, and E.R. Nunez 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)
43. M. Markman, J.A. Blessing, and R.D. Alvarez 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)
44. M.A. Hoffman, J.A. Blessing, and S.S. Lentz 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)
45. M.G. Kendall The treatment of ties in rank problems Biometrika 33 1945 239 251
46. C. Spearman The proof and measurement of association between two things Amer J Psychol 15 1904 72 101
47. R.A. Fisher Statistical Methods for Research Workers 1934 Edinburgh Oliver and Boyd 1970
48. C.R. Mehta, and N.R. Patel A network algorithm for performing Fisher's Exact test in r × c contingency tables J Amer Stat Assn 78 1983 427 434
49. E.L. Kaplan, and P. Meier Nonparemetric estimation from incomplete observations Am J Statis Assn 53 1958 457 481
50. D.R. Cox Regression models and life tables J R Stat Soc 34 1972 187 220 Series B
51. E.S. Han, P. Lin, and M. Wakabayashi Current status on biologic therapies in the treatment of epithelial ovarian cancer Curr Treat Options Oncol 10 2009 54 66
52. M. Markman Antiangiogenic drugs in ovarian cancer Expert Opin Pharmacother 10 2009 2269 2277
53. R.A. Burger, M.W. Sill, and B.J. Monk 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)
54. R.A. Burger, M.F. Brady, and M.A. Bookman Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC) or fallopian tube cancer (FTC): a Gynecologic Oncology Group study J Clin Oncol 28 2010 7s (Supplemental ASCO Abst #LBA1)
55. C. Aghajanian, J.A. Blessing, and K.M. Darcy A phase II evaluation of bortezomib in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer: a Gynecologic Oncology Group study Gynecol Oncol 115 2009 215 220
56. M.A. Bookman, K.M. Darcy, D. Clarke-Pearson, R.A. Boothby, and I.R. Horowitz Evaluation of monoclonal humanized anti-HER2 antibody (Trastuzumab) in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group J Clin Oncol 21 2 2003 283 290 (Pubitemid 46606157)
57. R. Schilder, M. Sill, and X. Chen Phase II study of gefitinib in patients with relapsed or persistent ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor mutations and immunohistochemical expression: a Gynecologic Oncology Group study Clin Cancer Res 11 2005 5539 5548 (Pubitemid 41060831)
58. R.J. Schilder, M.W. Sill, and R.B. Lee Phase II evaluation of imatinib methylate in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study J Clin Oncol 26 2008 3418 3425
59. D. Matei, M.W. Sill, K. DeGeest, and R.E. Bristow Phase II trial of sorafenib in persistent or recurrent epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC): a Gynecologic Oncology Group (GOG) study J Clin Oncol 26 2008 15S 301s (ASCO Abst#5537)
60. D. Matei, M.W. Sill, and H.A. Lankes Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis: a Gynecologic Oncology Group trial J Clin Oncol 29 2011 69 75
61. L. Usha, M. Sill, K. Darcy, D. Benbrook, J. Hurteau, and D. Michelin 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 Gynecol Oncol 116 2010 S16 (SGO Abst#37)
62. S.A. Cannistra, U.A. Matulonis, and R.T. Penson Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer J Clin Oncol 25 2007 5180 5186 (Pubitemid 350232248)
63. S.K. Pal, and R.A. Figlin Treatment options in metastatic renal cell carcinoma: focus on mTOR inhibitors Clin Med Insights Oncol 4 2010 43 53
64. N. Hay, and N. Sonenberg Upstream and downstream of mTOR Genes Dev 18 2004 1926 1945 (Pubitemid 39071573)
65. P. Frost, F. Moatamed, and B. Hoang In vivo antitumor effects of the mTOR inhibitor CCI-779 against human multiple myeloma cells in a xenograft model Blood 104 2004 4181 4187 (Pubitemid 39620172)
66. F.J. Giles, and M. Albitar Mammalian target of rapamycin as a therapeutic target in leukemia Curr Mol Med 5 2005 653 661 (Pubitemid 41824228)
67. J.J. Gibbons, R.T. Abraham, and K. Yu Mammalian target of rapamycin: discovery of rapamycin reveals a signaling pathway important for normal and cancer cell growth Semin Oncol 3 Suppl 2009 S3 S17
68. M.E. Feldman, B. Apsel, and A. Uotila Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2 PLoS Biol 7 2009 e38
69. K. Yu, L. Toral-Barza, and C. Shi Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin Cancer Res 69 2009 6232 6240
70. Targeting mTOR globally in cancer Thinking beyond rapamycin Cell Cycle 8 2009 3831 3837
71. N. Gulati, M. Karsy, and L. Albert Involvement of mTORC1 and mTORC2 in regulation of glioblastoma multiforme growth and motility Int J Oncol 35 2009 731 740
72. P. Frost, Y. Shi, B. Hoang, J. Gera, and A. Lichtenstein Regulation of D-cyclin translation inhibition in myeloma cells treated with mammalian target of rapamycin inhibitors: rationale for combined treatment with extracellular signal-regulated kinase inhibitors and rapamycin Mol Cancer Ther 8 2009 83 93
73. T. Bauernhofer, S. Zenahlik, and G. Hofmann Association of disease progression and poor overall survival with detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer Oncol Rep 13 2005 179 184
74. A. Nezos, N. Pissimisis, and P. Lembessis Detection of circulating tumor cells in bladder cancer patients Cancer Treat Rev 35 2009 272 279
75. A. Nezos, P. Lembessis, and A. Sourla Molecular markers detecting circulating melanoma cells by reverse transcription polymerase chain reaction: methodological pitfalls and clinical relevance Clin Chem Lab Med 47 2009 1 11
76. S. Maheswaran, L.V. Sequist, and S. Nagrath Detection of mutations in EGFR in circulating lung-cancer cells N Engl J Med 359 2008 366 377
77. K. Blumke, U. Bilkenroth, and U. Schmidt Detection of circulating tumor cells from renal carcinoma patients: experiences of a two-center study Oncol Rep 14 2005 895 899
78. W.J. Allard, J. Matera, and M.C. Miller Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases Clin Cancer Res 10 2004 6897 6904 (Pubitemid 39383039)
79. D.F. Hayes, T.M. Walker, and B. Singh Monitoring expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer Int J Oncol 21 2002 1111 1117