New therapeutic agents in ovarian cancer

Current Opinion in Obstetrics and Gynecology

Volumn 21, Issue 1, 2009, Pages 44-53

  Coilinson, Fiona ^a,b   Jayson, Gordon ^b  

^a UNIVERSITY OF LEEDS   (United Kingdom)

^b CHRISTIE HOSPITAL   (United Kingdom)

Author keywords

Epidermal growth factor receptor inhibitors; Epithelial ovarian cancer; Poly ADP ribose polymerase inhibitors; Targeted therapies; Tyrosine kinase inhibitors; Vascular endothelial growth factor inhibitors

Indexed keywords

ABAGOVOMAB; AC 125; AFLIBERCEPT; ANTIIDIOTYPIC ANTIBODY; ANTINEOPLASTIC AGENT; AZD 2281; BEVACIZUMAB; CARBOPLATIN; CEDIRANIB; CETUXIMAB; CISPLATIN; CYCLOPHOSPHAMIDE; DOCETAXEL; DOXORUBICIN; ERLOTINIB; FARLETUZUMAB; GEFITINIB; GEMCITABINE; KU 00594; LAPATINIB; MONOCLONAL ANTIBODY; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; OREGOVOMAB; OXALIPLATIN; PACLITAXEL; PERTUZUMAB; PLACEBO; SORAFENIB; SUNITINIB; TAXANE DERIVATIVE; TOPOTECAN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ASCITES; BLEEDING; CANCER CHEMOTHERAPY; CANCER RELAPSE; CANCER SURVIVAL; CARDIOTOXICITY; CLINICAL TRIAL; COLORECTAL CARCINOMA; CONSTIPATION; CYTOTOXICITY; DIARRHEA; DIGESTIVE SYSTEM FISTULA; DIGESTIVE SYSTEM PERFORATION; DRUG BINDING; DRUG HALF LIFE; DRUG TOLERABILITY; DYSPHONIA; FATIGUE; GASTROINTESTINAL OBSTRUCTION; GASTROINTESTINAL TOXICITY; HEADACHE; HUMAN; HYPERTENSION; HYPOTHYROIDISM; INTESTINE PERFORATION; KIDNEY CARCINOMA; LEUKOENCEPHALOPATHY; LUNG NON SMALL CELL CANCER; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROTOXICITY; NEUTROPENIA; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PRIORITY JOURNAL; PROTEINURIA; PULMONARY HYPERTENSION; RASH; REVIEW; THROMBOEMBOLISM; TREATMENT OUTCOME; TREATMENT RESPONSE; VOMITING; WOUND HEALING IMPAIRMENT;

ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CARBOPLATIN; DRUG ADMINISTRATION ROUTES; FEMALE; HUMANS; NEOVASCULARIZATION, PATHOLOGIC; OVARIAN NEOPLASMS; PACLITAXEL; POLY ADENOSINE DIPHOSPHATE RIBOSE; PROTEIN KINASE INHIBITORS; PROTEINS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECEPTOR, EPIDERMAL GROWTH FACTOR; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 59149097288     PISSN: 1040872X     EISSN: None     Source Type: Journal    
DOI: 10.1097/GCO.0b013e32831ffe71     Document Type: Review

References (115)

1. du Bois A, Quinn M, Thigpen T, et al., 2004 consensus statements on the management of ovarian cancer: final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004). Ann Oncol 2005; 16 (Suppl 8):viii7-viii12.
2. Bookman M. GOG0182-ICON5: 5-arm phase III randomized trial of paclitaxel (P) and carboplatin (C) vs combinations with gemcitabine (G), PEG- lipososomal doxorubicin (D), or topotecan (T) in patients (pts) with advanced- stage epithelial ovarian (EOC) or primary peritoneal (PPC) carcinoma. J Clin Oncol 2006; 24 (18 Suppl).
3. Hoskins PJ, Vergote I, Stuart G, et al., A phase III trial of cisplatin plus topotecan followed by paclitaxel plus carboplatin versus standard carboplatin plus paclitaxel as first line chemotherapy in women with newly diagnosed advanced epithelial ovarain cancer (EOC) (OV.16) [abstract #5505]. J Clin Oncol 2008; 26 (15 Suppl).
4. Isonishi S, Yasuda M, Takahashi N, et al., Randomised phase III trial of conventional paclitaxel and carboplatin (c-TC) versus dose dense weekly paclitaxel and carboplatin (dd-TC) in women with advanced epithelial ovarian cancer, fallopian tube or primary peritoneal cancer: Japanese Gynecologic Oncology [abstract #5506]. J Clin Oncol 2008; 26 (15 Suppl).
5. Rose PG, Smrekar M, Fusco N. A phase II trial of weekly paclitaxel and every 3 weeks of carboplatin in potentially platinum-sensitive ovarian and peritoneal carcinoma. Gynecol Oncol 2005; 96:296-300.
6. Sehouli J, Stengel D, Mustea A, et al., Weekly paclitaxel and carboplatin (PC- W) for patients with primary advanced ovarian cancer: results of a multicenter phase-ll study of the NOGGO. Cancer Chemother Pharmacol 2008; 61:243-250.
7. Sparano JA, Wang M, Martino S, et al., Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008; 358:1663-1671.
8. Seidman AD, Berry D, Cirrincione C, et al., Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol 2008; 26:1642-1649.
9. Kirmani S, Braly PS, McClay EF, et al., A comparison of intravenous versus intraperitoneal chemotherapy for the initial treatment of ovarian cancer. Gynecol Oncol 1994; 54:338-344.
10. Alberts DS, Liu PY, Hannigan EV, et al., Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 1996; 335:1950-1955.
11. Polyzos A, Tsavaris N, Kosmas C, et al., A comparative study of intraperitoneal carboplatin versus intravenous carboplatin with intravenous cyclophosphamide in both arms as initial chemotherapy for stage III ovarian cancer. Oncology 1999; 56:291 -296.
12. Gadducci A, Carnino F, Chiara S, et al., Intraperitoneal versus intravenous cisplatin in combination with intravenous cyclophosphamide and epidoxorubicin in optimally cytoreduced advanced epithelial ovarian cancer: a randomized trial of the Gruppo Oncologico Nord-Ovest. Gynecol Oncol 2000; 76:157-162.
13. Markman M, Bundy BN, Alberts DS, et al., Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small- volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol 2001; 19:1001 -1007.
14. Yen MS, Juang CM, Lai CR, et al., Intraperitoneal cisplatin-based chemotherapy vs. intravenous cisplatin-based chemotherapy for stage III optimally cytoreduced epithelial ovarian cancer. Int J Gynaecol Obstet 2001; 72:55-60.
15. Armstrong DK, Bundy B, Wenzel L, et al., Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006; 354:34-43.
16. Schumacher JJ, Dings RP, Cosin J, et al., Modulation of angiogenic phenotype alters tumorigenicity in rat ovarian epithelial cells. Cancer Res 2007; 67:3683-3690. This study demonstrates how important angiogenesis is not only in the progression, but also in the development of EOC.
17. Zhang A, Meng L, Wang Q, et al., Enhanced in vitro invasiveness of ovarian cancer cells through up-regulation of VEGF and induction of MMP-2. Oncol Rep 2006; 15:831-836.
18. Huang S, Robinson JB, Deguzman A, et al., Blockade of nuclear factor- kappaB signaling inhibits angiogenesis and tumorigenicity of human ovarian cancer cells by suppressing expression of vascular endothelial growth factor and interleukin 8. Cancer Res 2000; 60:5334-5339.
19. Yukita A, Asano M, Okamoto T, et al., Suppression of ascites formation and re-accumulation associated with human ovarian cancer by an anti-VPF monoclonal antibody in vivo. Anticancer Res 2000; 20:155-160.
20. Byrne AT, Ross L, Holash J, et al., Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin Cancer Res 2003; 9:5721 - 5728.
21. Hu L, Hofmann J, Zaloudek C, et al., Vascular endothelial growth factor immunoneutralization plus Paclitaxel markedly reduces tumor burden and ascites in athymic mouse model of ovarian cancer. Am J Pathol 2002; 161:1917-1924.
22. Mesiano S, Ferrara N, Jaffe RB. Role of vascular endothelial growth factor in ovarian cancer: inhibition of ascites formation by immunoneutralization. Am J Pathol 1998; 153:1249-1256.
23. Paley PJ, Staskus KA, Gebhard K, et al., Vascular endothelial growth factor expression in early stage ovarian carcinoma. Cancer 1997; 80:98-106.
24. Yamamoto S, Konishi I, Mandai M, et al., Expression of vascular endothelial growth factor (VEGF) in epithelial ovarian neoplasms: correlation with clinicopathology and patient survival, and analysis of serum VEGF levels. Br J Cancer 1997; 76:1221-1227.
25. Cooper BC, Ritchie JM, Broghammer CL, et al., Preoperative serum vascular endothelial growth factor levels: significance in ovarian cancer. Clin Cancer Res 2002; 8:3193-3197.
26. Zebrowski BK, Liu W, Ramirez K, et al., Markedly elevated levels of vascular endothelial growth factor in malignant ascites. Ann Surg Oncol 1999; 6:373-378.
27. Kraft A, Weindel K, Ochs A, et al., Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease. Cancer 1999; 85:178-187.
28. Hurwitz H, Fehrenbacher L, Novotny W, et al., Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350:2335-2342.
29. Presta L, Chen H, O'Connor S, et al., Humanisation of an antivascular endothelial growth factor monoclonal antibody for the therapy of solid tumours and other disorders. Cancer Research 1997; 57:4593-4599.
30. Yang JC, Haworth L, Sherry RM, et al., A randomized trial of bevacizumab, an antivascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003; 349:427-434.
31. Llovet JM, Ricci S, Mazzaferro V, et al., Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359:378-390.
32. Verheul HM, Hoekman K, Jorna AS, et al., Targeting vascular endothelial growth factor blockade: ascites and pleural effusion formation. Oncologist 2000; 5 (Suppl 1):45-50.
33. Numnum TM, Rocconi RP, Whitworth J, Barnes MN. The use of bevacizumab to palliate symptomatic ascites in patients with refractory ovarian carcinoma. Gynecol Oncol 2006; 102:425-428.
34. Hamilton CA, Maxwell GL, Chernofsky MR, et al., Intraperitoneal bevacizumab for the palliation of malignant ascites in refractory ovarian cancer. Gynecol Oncol 2008; 111:530-532. The first report of bevacizumab used intraperitoneally.
35. El-Shami K, Elsaid A, El-kerm Y. Open-label safety and efficacy pilot trial of intraperitoneal bevacizumab as palliative treatment in refractory malignant ascites [abstract #9043]. J Clin Oncol 2007; 25 (18 Suppl).
36. Burger RA, Sill MW, Monk BJ, et al., Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2007; 25:5165-5171.
37. Cannistra SA, Matulonis UA, Penson RT, et al., Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 2007; 25:5180-5186.
38. Penson RT, Cannistra SA, Seiden CN, et al., Phase II study of carboplatin, paclitaxel and bevacizumab as first line chemotherapy and consolidation for advanced mullerian tumours [abstract #5020]. J Clin Oncol 2006; 24 (18 Suppl).
39. Garcia AA, Hirte H, Fleming G, et al., Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol 2008; 26:76-82.
40. Freiberg G, Oza A, Morgan A, et al., Bevacizumab (B) plus erlotinib (E) for patients (pts) with recurrent ovarian (OC) and fallopian tube (FT) cancer: preliminary results of a multi-center phase II trial [abstract #5018], J Clin Oncol 2006; 24 (18 Suppl).
41. Mancuso MR, Davis R, Norberg SM, et al., Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest 2006; 116:2610-2621.
42. Han ES, Monk BJ. What is the risk of bowel perforation associated with bevacizumab therapy in ovarian cancer? Gynecol Oncol 2007; 105:3-6.
43. Wright JD, Secord AA, Numnum TM, et al., A multiinstitutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer. Int J Gynecol Cancer 2008; 18:400-406. The study looking at which patients were more likely to experience toxicity from bevacizumab and discovered that most often patients who developed gastrointestinal perforation were those who were responding to treatment.
44. Azad N, Posadas E, Kwitkowski V, et al., Increased efficacy and toxicity with combination anti-VEGF therapy using sorafenib and bevacizumab [abstract #3004]. J Clin Oncol 2006; 24 (Suppl 18).
45. Azad NS, Posadas EM, Kwitkowski VE, et al., Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J Clin Oncol 2008; 26:3709-3714. A study showing increased toxicity with combination anti-VEGF and TKI therapy demonstrating that if study in this area continues, then dose modification will be required.
46. Viloria-Petit A, Crombet T, Jothy S, et al., Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis. Cancer Res 2001; 61:5090-5101.
47. Nimeiri HS, Oza AM, Morgan RJ, et al., Efficacy and safety of bevacizumab plus erlotinib for patients with recurrent ovarian, primary peritoneal, and fallopian tube cancer: a trial of the Chicago, PMH, and California Phase II Consortia. Gynecol Oncol 2008; 110:49-55.
48. Hirte H, Vidal L, Fleming G, et al., A phase II study of cediranib (AZD2171) in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: final results of the PMH, Chicago and California consortia trial [abstract #5521]. J Clin Oncol 2008; 26 (15 Suppl).
49. Matulonis UA, Berlin ST, Krasner CN, et al., Cediranib (AZD2171) is an active agent in recurrent epithelial ovarian cancer [abstract #5501]. J Clin Oncol 2008; 26 (15 Suppl).
50. Hu L, Hofmann J, Holash J, et al., Vascular endothelial growth factor trap combined with paclitaxel strikingly inhibits tumor and ascites, prolonging survival in a human ovarian cancer model. Clin Cancer Res 2005; 11:6966- 6971.
51. Tew W, Colombo N, Ray-Caquard I, et al., VEGF-Trap for patients with recurrent platinum resistant epithelial ovarian cancer [abstract #5508]. J Clin Oncol 2007; 25 (18 Suppl).
52. Biagi J, Oza A, Grimshaw R, et al., A phase II study of sunitinib (SU11248) in patients with recurrent epithelial ovarian cancer, fallopian tube or primary peritoneal carcinoma: NCIC CTG IND 185 [abstract #5522]. J Clin Oncol 2008; 26 (15 Suppl).
53. Kennedy AW, Biscotti CV, Hart WR, Webster KD. Ovarian clear cell adenocarcinoma. Gynecol Oncol 1989; 32:342-349.
54. Zorn KK, Bonome T, Gangi L, et al., Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer. Clin Cancer Res 2005; 11:6422-6430.
55. Rauh-Hain JA, Penson RT. Potential benefit of sunitinib in recurrent and refractory ovarian clear cell adenocarcinoma. Int J Gynecol Cancer 2007; 18:934-936.
56. Matei D, Sill M, DeGeest K, Bristow R. Phase II trial of sorafenib in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a GOG study [abstract #5537]. J Clin Oncol 2008; 26 (Suppl).
57. Welch S, Hirte H, Schildlder R, et al., Phase II study of sorafenib (BAY 43- 9006) in combination with gemcitabine in recurrent epithelial ovarian cancer: a PMH phase II consortium trial [abstract #5084]. J Clin Oncol 2006; (15 Suppl).
58. Ciardiello F, Tortora G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 2001; 7:2958- 2970.
59. Arteaga CL. Overview of epidermal growth factor receptor biology and its role as a therapeutic target in human neoplasia. Semin Oncol 2002; 29:3-9.
60. Sridhar SS, Seymour L, Shepherd FA. Inhibitors of epidermal-growth-factor receptors: a review of clinical research with a focus on nonsmall-cell lung cancer. Lancet Oncol 2003; 4:397-406.
61. Bartlett JM, Langdon SP, Simpson BJ, et al., The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer. Br J Cancer 1996; 73:301-306.
62. Fischer-Colbrie J, Witt A, Heinzl H, et al., EGFR and steroid receptors in ovarian carcinoma: comparison with prognostic parameters and outcome of patients. Anticancer Res 1997; 17:613-619.
63. Alper O, Bergmann-Leitner ES, Bennett TA, et al., Epidermal growth factor receptor signaling and the invasive phenotype of ovarian carcinoma cells. J Natl Cancer Inst 2001; 93:1375-1384.
64. Skirnisdottir I, Sorbe B, Seidal T. The growth factor receptors HER-2/neu and EGFR, their relationship, and their effects on the prognosis in early stage (FIGO l-ll) epithelial ovarian carcinoma. Int J Gynecol Cancer 2001; 11:119- 129.
65. Psyrri A, Kassar M, Yu Z, et al., Effect of epidermal growth factor receptor expression level on survival in patients with epithelial ovarian cancer. Clin Cancer Res 2005; 11:8637-8643.
66. Berchuck A, Rodriguez GC, Kamel A, et al., Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. I. Correlation of receptor expression with prognostic factors in patients with ovarian cancer. Am J Obstet Gynecol 1991; 164:669-674.
67. Kohler M, Bauknecht T, Grimm M, et al., Epidermal growth factor receptor and transforming growth factor alpha expression in human ovarian carcinomas. Eur J Cancer 1992; 28A: 1432-1437.
68. Elie C, Geay JF, Morcos M, et al., Lack of relationship between EGFR-1 immunohistochemical expression and prognosis in a multicentre clinical trial of 93 patients with advanced primary ovarian epithelial cancer (GINECO group). Br J Cancer 2004; 91:470-475.
69. de Graeff P, Crijns AP, Ten Hoor KA, et al., The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer. Br J Cancer 2008; 99:341 -349.
70. Albanell J, Gascon P. Small molecules with EGFR-TK inhibitor activity. Curr Drug Targets 2005; 6:259-274.
71. Sewell JM, Macleod KG, Ritchie A, et al., Targeting the EGF receptor in ovarian cancer with the tyrosine kinase inhibitor ZD 1839 ('Iressa'). Br J Cancer 2002; 86:456-462.
72. Fujimura M, Hidaka T, Saito S. Selective inhibition of the epidermal growth factor receptor by ZD1839 decreases the growth and invasion of ovarian clear cell adenocarcinoma cells. Clin Cancer Res 2002; 8:2448-2454.
73. Slomovitz BM, Coleman RL, Levenback C, et al., Phase I study of weekly topotecan and gefitinib in patients with platinum resistant ovarian, peritoneal or fallopian tube cancer [abstract #5090], J Clin Oncol 2006; 24 (18 Suppl).
74. Hariprasad R, Kumar L, Patnaik R, et al., Maintenance therapy in EOC: could EGFR inhibitor gefitinib be a candidate drug [abstract #15046]. J Clin Oncol 2006; 24 (18 Suppl).
75. Schilder RJ, Sill MW, Chen X, et al., 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 2005; 11:5539-5548.
76. Posadas EM, Liel MS, Kwitkowski V, et al., A phase II and pharmacodynamic study of gefitinib in patients with refractory or recurrent epithelial ovarian cancer. Cancer 2007; 109:1323-1330.
77. Van Schaeybroeck S, Kyula J, Kelly DM, et al., Chemotherapy-induced epidermal growth factor receptor activation determines response to combined gefitinib/chemotherapy treatment in nonsmall cell lung cancer cells. Mol Cancer Ther 2006; 5:1154-1165.
78. Lynch TJ, Bell DW, Sordella R, et al., Activating mutations in the epidermal growth factor receptor underlying responsiveness of nonsmall-cell lung cancer to gefitinib. N Engl J Med 2004; 350:2129-2139.
79. Paez JG, Janne PA, Lee JC, et al., EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304:1497-1500.
80. Bull Phelps SL, Schorge JO, Peyton MJ, et al., Implications of EGFR inhibition in ovarian cancer cell proliferation. Gynecol Oncol 2008; 109:411-417.
81. Gordon AN, Finkler N, Edwards RP, et al., Efficacy and safety of erlotinib HCI, an epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor, in patients with advanced ovarian carcinoma: results from a phase II multi - center study. Int J Gynecol Cancer 2005; 15:785-792.
82. Vasey PA, Gore M, Wilson R, et al., A phase lb trial of docetaxel, carboplatin and erlotinib in ovarian, fallopian tube and primary peritoneal cancers. Br J Cancer 2008; 98:1774-1780.
83. Higgins B, Kolinsky K, Smith M, et al., Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in human nonsmall cell lung cancer tumor xenograft models. Anticancer Drugs 2004; 15:503-512.
84. Marth C, Egle D, Auer D, et al., Modulation of CA-125 tumor marker shedding in ovarian cancer cells by erlotinib or cetuximab. Gynecol Oncol 2007; 105:716-721.
85. Azad NS, Annunziata CM, Steinberg SM, et al., Lack of reliability of CA125 response criteria with anti-VEGF molecularly targeted therapy. Cancer 2008; 112:1726-1732. Potentially important work demonstrating that CA 125 does not alter in the same way in response to anti-VEGF therapy as it does to conventional chemotherapy. This has implications for utilizing CA 125 response in early phase clinical trials to assist in deciding which drugs should be continued for testing.
86. Rivkin S, Muller C, Iriarte D, et al., Phase l/ll lapatinib plus carboplatin and paclitaxel in stage III or IV relapsed ovarain cancer patients [abstract #5556]. J Clin Oncol 2008; 26 (15 Suppl).
87. Burtness B, Goldwasser MA, Flood W, et al., Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol 2005; 23:8646-8654.
88. Konner J, Schilder RJ, DeRosa FA, et al., A phase II study of cetuximab/paclitaxel/carboplatin for the initial treatment of advanced-stage ovarian, primary peritoneal, or fallopian tube cancer. Gynecol Oncol 2008; 110:140-145.
89. Secord AA, Blessing JA, Armstrong DK, et al., Phase II trial of cetuximab and carboplatin in relapsed platinum-sensitive ovarian cancer and evaluation of epidermal growth factor receptor expression: a Gynecologic Oncology Group study. Gynecol Oncol 2008; 108:493-499.
90. Cunningham D, Humblet Y, Siena S, et al., Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351:337-345.
91. Gordon MS, Matei D, Aghajanian C, et al., Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer: potential predictive relationship with tumor HER2 activation status. J Clin Oncol 2006; 24:4324-4332.
92. Glenn D, Ueland F, Bicher A, et al., A randomised phase II trial with gemcitabine with or without pertuzumab in platinum resistant ovarian cancer [abstract #13001]. J Clin Oncol 2006; 24 (18 Suppl).
93. Risch HA, McLaughlin JR, Cole DE, et al., Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada, J Natl Cancer Inst 2006; 98:1694-1706.
94. Farmer H, McCabe N, Lord CJ, et al., Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005; 434:917- 921.
95. Fong P, Boss D, Carden C, et al., AZD2281 (KU-0059436), a PARP (poly ADP-ribose polymerase) inhibitor with single agent anticancer activity in patients with BRCA deficient ovarian cancer: results from a phase I study [abstract #5510). J Clin Oncol 2008; 26 (15 Suppl):295s. A very promising early data from the use of a PARP inhibitor in patients with EOC and inherited BRCA mutations. This may represent a step towards stratified treatment for patients with EOC.
96. Zhang L, Conejo-Garcia JR, Katsaros D, et al., Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003; 348:203-213.
97. Curiel TJ, Coukos G, Zou L, et al., Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat' Med 2004; 10:942-949.
98. Noujaim AA, Schultes BC, Baum RP, Madiyalakan R. Induction of CA125- specific B and T cell responses in patients injected with MAb-B43.13- evidence for antibody-mediated antigen-processing and presentation of CA125 in vivo. Cancer Biother Radiopharm 2001; 16:187-203.
99. Baum RP, Noujaim AA, Nanci A, et al., Clinical course of ovarian cancer patients under repeated stimulation of HAMA using MAb OC125 and B43.13. Hybridoma 1993; 12:583-589.
100. Ehlen TG, Hoskins PJ, Miller D, et al., A pilot phase 2 study of oregovomab murine monoclonal antibody to CA125 as an immunotherapeutic agent for recurrent ovarian cancer. Int J Gynecol Cancer 2005; 15:1023- 1034.
101. Berek J, Taylor PT, McGuire WP, et al., Evaluation of maintenance mono- immmunotherapy to improve outcomes in advanced ovarian cancer (OV CA) [abstract #5507]. J Clin Oncol 2008; 26 (15 Suppl).
102. Wagner U, Schlebusch H, Kohler S, et al., Immunological responses to the tumor-associated antigen CA125 in patients with advanced ovarian cancer induced by the murine monoclonal antiidiotype vaccine ACA125. Hybridoma 1997; 16:33-40.
103. Jerne NK. Towards a network theory of the immune system. Ann Immunol (Paris) 1974; 125C:373-389.
104. Sabbatini P, Dupont J, Aghajanian C, et al., Phase I study of abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Clin Cancer Res 2006; 12:5503-5510.
105. Wagner U, Kohler S, Reinartz S, et al., Immunological consolidation of ovarian carcinoma recurrences with monoclonal antiidiotype antibody ACA125: immune responses and survival in palliative treatment. Clin Cancer Res 2001; 7:1154-1162. [see The biology behind: Foon KA, Bhattacharya- Chatterjee M, Are solid tumor antiidiotype vaccines ready for prime time? Clin Cancer Res 2001; 7:1112-1115].
106. Reinartz S, Kohler S, Schlebusch H, et al., Vaccination of patients with advanced ovarian carcinoma with the antiidiotype ACA125: immunological response and survival (phase Ib/ll). Clin Cancer Res 2004; 10:1580-1587.
107. Reinartz S, Wagner U, Giffels P, et al., Immunological properties of a single- chain fragment of the antiidiotypic antibody ACA125. Cancer Immunol Immunother 2000; 49:186-192.
108. Pfisterer J, du Bois A, Sehouli J, et al., The antiidiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR. Ann Oncol 2006; 17:1568-1577.
109. Kalli KR, Oberg AL, Keeney GL, et al., Folate receptor alpha as a tumor target in epithelial ovarian cancer. Gynecol Oncol 2008; 108:619-626.
110. Parker N, Turk MJ, Westrick E, et al., Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem 2005; 338:284-293.
111. Knutson KL, Krco CJ, Erskine CL, et al., T-cell immunity to the folate receptor alpha is prevalent in women with breast or ovarian cancer. J Clin Oncol 2006; 24:4254-4261.
112. Kalli KR. MORAb-003, a fully humanized monoclonal antibody against the folate receptor alpha, for the potential treatment of epithelial ovarian cancer. Curr Opin Investig Drugs 2007; 8:1067-1073.
113. Konner J, Ahmed S, Gerst S, et al., Phase I study of MORAb-003, a humanized anti-folate receptor-alpha monoclonal antibody, in platinum resistant ovarain cancer [abstract 5027]. J Clin Oncol 2006; 24 (18 Suppl).
114. Bell-McGuin K, Konner J, Pandit-Taskar N, et al., A phase I study of MORAb- 003, a humanised monoclonal antibody against folate receptor alpha, in advanced epithelial ovarian cancer [abstract #5517]. J Clin Oncol 2008; 26 (15 Suppl).
115. Armstrong D, Bicher A, Coleman R, et al., Exploratory phase II efficacy study of MORAb-003, a monoclonal antibody against folate receptor alpha, in platinum-sensitive ovarian cancer in first relapse [abstract #5508]. J Clin Oncol 2008; 26 (15 Suppl).