Targeted treatment of recurrent platinum-resistant ovarian cancer : current and emerging therapies

Correspondence: Gina M Mantia-Smaldone Division of Gynecologic Oncology, Hospital of the University of Pennsylvania, 3rd floor, PCAM, 34th and Spruce Streets, Philadelphia, PA 19104, USA Tel +1 215-662-3327 Fax +1 215-573-5408 email gina.mantia@uphs.upenn.edu Abstract: With advances in surgical techniques and chemotherapeutic agents, mortality rates from epithelial ovarian cancer (EOC) have slightly decreased over the last 30 years. However, EOC still ranks as the most deadly gynecologic cancer with an overall 5-year survival rate of 45%. Prognosis is especially disappointing for women with platinum-resistant disease, where 80% of patients will fail to respond to available therapies. Emerging treatment strategies have subsequently focused on targets which are integral to tumor growth and metastasis. In this review, we will focus on those innovative agents currently under investigation in clinical trials.

[1]  Ahir Gopaldas.  Therapy , 2016, Indian Journal of Nuclear Medicine : IJNM : The Official Journal of the Society of Nuclear Medicine, India.

[2]  A. Oza,et al.  A phase II study of sunitinib in patients with recurrent epithelial ovarian and primary peritoneal carcinoma: an NCIC Clinical Trials Group Study. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[3]  J. Ledermann,et al.  Targeted trials in ovarian cancer. , 2010, Gynecologic oncology.

[4]  M. Friedlander,et al.  A Phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. , 2010, Gynecologic oncology.

[5]  B. Karlan,et al.  Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  A. Tutt,et al.  Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial , 2010, The Lancet.

[7]  P. Kantoff,et al.  Sipuleucel-T immunotherapy for castration-resistant prostate cancer. , 2010, The New England journal of medicine.

[8]  B. Monk,et al.  Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  P. Murawa,et al.  The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial , 2010, International journal of cancer.

[10]  M. Shahin,et al.  A phase II evaluation of mifepristone in the treatment of recurrent or persistent epithelial ovarian, fallopian or primary peritoneal cancer: a gynecologic oncology group study. , 2010, Gynecologic oncology.

[11]  C. Runowicz,et al.  Ovarian cancer immunotherapy: opportunities, progresses and challenges , 2010, Journal of Hematology & Oncology.

[12]  Hang Lee,et al.  Phase II trial of GM-CSF in women with asymptomatic recurrent müllerian tumors. , 2010, Gynecologic oncology.

[13]  K. Ushijima.  Treatment for Recurrent Ovarian Cancer—At First Relapse , 2009, Journal of oncology.

[14]  R. Slavcev,et al.  Addressing the challenge: current and future directions in ovarian cancer therapy. , 2009, Current gene therapy.

[15]  J. Kavanagh,et al.  What Is the Benefit of Bevacizumab Combined with Chemotherapy in Patients with Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Malignancies? , 2009, Journal of chemotherapy.

[16]  S. Canevari,et al.  (177)Lu- labeled MOv18 as compared to (131)I- or (90)Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts. , 2009, Nuclear medicine and biology.

[17]  B. Monk,et al.  Changing the Paradigm in the Treatment of Platinum-Sensitive Recurrent Ovarian Cancer: From Platinum Doublets to Nonplatinum Doublets and Adding Antiangiogenesis Compounds , 2009, International Journal of Gynecologic Cancer.

[18]  M. Markman.  Optimal Management of Recurrent Ovarian Cancer , 2009, International Journal of Gynecologic Cancer.

[19]  Martin A. Cheever,et al.  The Prioritization of Cancer Antigens: A National Cancer Institute Pilot Project for the Acceleration of Translational Research , 2009, Clinical Cancer Research.

[20]  D. Silasi,et al.  Overexpression of Epithelial Cell Adhesion Molecule in Primary, Metastatic, and Recurrent/Chemotherapy-Resistant Epithelial Ovarian Cancer: Implications for Epithelial Cell Adhesion Molecule-Specific Immunotherapy , 2009, International Journal of Gynecologic Cancer.

[21]  Robert S Mannel,et al.  Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  T. O'brien,et al.  Cellular immunotherapy for ovarian cancer , 2009, Expert opinion on biological therapy.

[23]  R. Iyer,et al.  A phase II study of GM-CSF and rIFN-gamma1b plus carboplatin for the treatment of recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer. , 2009, Gynecologic oncology.

[24]  L. Downs,et al.  A phase II study of fulvestrant in the treatment of multiply-recurrent epithelial ovarian cancer. , 2009, Gynecologic oncology.

[25]  K. Devarajan,et al.  Phase II trial of single agent cetuximab in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with the potential for dose escalation to rash. , 2009, Gynecologic oncology.

[26]  I. Pastan,et al.  Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains , 2009, Proceedings of the National Academy of Sciences.

[27]  G. Jayson,et al.  Antiangiogenic drugs in ovarian cancer , 2008, British Journal of Cancer.

[28]  B. Vanderhyden,et al.  Phase II evaluation of imatinib mesylate in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group Study. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  M. Deavers,et al.  Efficacy of letrozole in the treatment of recurrent platinum- and taxane-resistant high-grade cancer of the ovary or peritoneum. , 2008, Gynecologic oncology.

[30]  A. Baron,et al.  Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer. , 2008, Biochimica et biophysica acta.

[31]  S. Rosenberg,et al.  Adoptive cell transfer: a clinical path to effective cancer immunotherapy , 2008, Nature Reviews Cancer.

[32]  D. Neuberg,et al.  Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients , 2008, Proceedings of the National Academy of Sciences.

[33]  K. Kalli.  MORAb-003, a fully humanized monoclonal antibody against the folate receptor alpha, for the potential treatment of epithelial ovarian cancer. , 2007, Current opinion in investigational drugs.

[34]  Michael W Sill,et al.  Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  Howard Mackey,et al.  Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  D. Provencher,et al.  A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens , 2007, British Journal of Cancer.

[37]  R. Steinman,et al.  Dendritic cells: Understanding immunogenicity , 2007, European journal of immunology.

[38]  I. Cree,et al.  A prospective randomized controlled trial of tumour chemosensitivity assay directed chemotherapy versus physician's choice in patients with recurrent platinum-resistant ovarian cancer , 2007, Anti-cancer drugs.

[39]  D. Germano,et al.  Gemcitabine Combined with Oxaliplatin (GEMOX) as Salvage Treatment in Elderly Patients with Advanced Ovarian Cancer Refractory or Resistant to Platinum: a Single Institution Experience , 2007, Journal of chemotherapy.

[40]  I. Pastan,et al.  Phase I Study of SS1P, a Recombinant Anti-Mesothelin Immunotoxin Given as a Bolus I.V. Infusion to Patients with Mesothelin-Expressing Mesothelioma, Ovarian, and Pancreatic Cancers , 2007, Clinical Cancer Research.

[41]  D. Mutch,et al.  Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  G. Mantovani,et al.  A multicenter phase II study of pegylated liposomal doxorubicin and oxaliplatin in recurrent ovarian cancer. , 2007, Gynecologic oncology.

[43]  D. Alberts,et al.  Randomized trial of pegylated liposomal doxorubicin (PLD) plus carboplatin versus carboplatin in platinum-sensitive (PS) patients with recurrent epithelial ovarian or peritoneal carcinoma after failure of initial platinum-based chemotherapy (Southwest Oncology Group Protocol S0200). , 2007, Gynecologic oncology.

[44]  N. Senzer,et al.  Novel phase II study design of MORAb-003, a monoclonal antibody against folate receptor alpha in platinum-sensitive ovarian cancer in first relapse , 2007 .

[45]  A. Lopes,et al.  Decreased intraperitoneal disease recurrence in epithelial ovarian cancer patients receiving intraperitoneal consolidation treatment with yttrium‐90‐labeled murine HMFG1 without improvement in overall survival , 2007, International journal of cancer.

[46]  H. Gabra,et al.  Antiestrogen Therapy Is Active in Selected Ovarian Cancer Cases: The Use of Letrozole in Estrogen Receptor–Positive Patients , 2007, Clinical Cancer Research.

[47]  Jimmy P. Xu,et al.  Preclinical antitumor activity of the oral platinum analog satraplatin , 2007, Cancer Chemotherapy and Pharmacology.

[48]  S. Steinberg,et al.  A phase II and pharmacodynamic study of gefitinib in patients with refractory or recurrent epithelial ovarian cancer , 2007, Cancer.

[49]  M. Inbar,et al.  Efficacy and toxicity of weekly topotecan in recurrent epithelial ovarian and primary peritoneal cancer. , 2007, Gynecologic oncology.

[50]  David Cameron,et al.  2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial , 2007, The Lancet.

[51]  D. Camidge,et al.  A phase I dose-escalation study of weekly IMC-1121B, a fully human anti-vascular endothelial growth factor receptor 2 (VEGFR2) IgG1 monoclonal antibody (Mab), in patients (pts) with advanced cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[52]  Gang Wang,et al.  A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer , 2006, Clinical Cancer Research.

[53]  E. Eisenhauer,et al.  Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[54]  A. Reuss,et al.  The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[55]  A. Iasonos,et al.  Phase I Study of Abagovomab in Patients with Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer , 2006, Clinical Cancer Research.

[56]  Alan Ashworth,et al.  Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. , 2006, Cancer research.

[57]  P. Sabbatini,et al.  Phase I study of MORAb-003, a humanized anti-folate receptor-alpha monoclonal antibody, in platinum resistant ovarian cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[58]  D. Bodurka,et al.  Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant epithelial ovarian and primary peritoneal cancers. , 2006, Gynecologic oncology.

[59]  G. Mor,et al.  Molecular mechanism of phenoxodiol‐induced apoptosis in ovarian carcinoma cells , 2006, Cancer.

[60]  Gerd Ritter,et al.  Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[61]  T. Curiel,et al.  Regulatory T Cells in Ovarian Cancer: Biology and Therapeutic Potential , 2005, American journal of reproductive immunology.

[62]  D. Burns,et al.  Estrogen receptor-alpha mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen. , 2005, Endocrine-related cancer.

[63]  G. Jayson,et al.  Phase II trial of tamoxifen and goserelin in recurrent epithelial ovarian cancer , 2005, British Journal of Cancer.

[64]  A. Godwin,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 , 2005, Clinical Cancer Research.

[65]  A. Tomassetti,et al.  90Y Labeling of monoclonal antibody MOv18 and preclinical validation for radioimmunotherapy of human ovarian carcinomas , 2005, Cancer Immunology, Immunotherapy.

[66]  S. Barry,et al.  AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. , 2005, Cancer research.

[67]  C. Balañà,et al.  Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[68]  S. Rosenberg,et al.  Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[69]  G. Cirelli,et al.  Second‐line therapy of advanced ovarian cancer with GnRH analogs , 2004, International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.

[70]  M. Somerfield,et al.  American Society of Clinical Oncology Technology Assessment: chemotherapy sensitivity and resistance assays. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[71]  George Coukos,et al.  Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival , 2004, Nature Medicine.

[72]  K. Swenerton,et al.  A pilot phase 2 study of oregovomab murine monoclonal antibody to CA125 as an immunotherapeutic agent for recurrent ovarian cancer , 2004, International Journal of Gynecologic Cancer.

[73]  T. Whiteside,et al.  CA125- and tumor-specific T-cell responses correlate with prolonged survival in oregovomab-treated recurrent ovarian cancer patients. , 2004, Gynecologic oncology.

[74]  Steve Nicholson,et al.  A phase I trial of idiotypic vaccination with HMFG1 in ovarian cancer , 2004, Cancer Immunology, Immunotherapy.

[75]  C. Bucana,et al.  Expression of platelet-derived growth factor and activated receptor in clinical specimens of epithelial ovarian cancer and ovarian carcinoma cell lines. , 2004, Gynecologic oncology.

[76]  R. Kreienberg,et al.  Vaccination of Patients with Advanced Ovarian Carcinoma with the Anti-Idiotype ACA125 , 2004, Clinical Cancer Research.

[77]  V. Boddi,et al.  Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma , 2003, International Journal of Gynecologic Cancer.

[78]  D. Spriggs.  Optimal sequencing in the treatment of recurrent ovarian cancer. , 2003, Gynecologic oncology.

[79]  C. Verschraegen,et al.  Phase II study of cetrorelix, a luteinizing hormone-releasing hormone antagonist in patients with platinum-resistant ovarian cancer. , 2003, Gynecologic oncology.

[80]  M. Markman,et al.  Phase 2 trial of single-agent gemcitabine in platinum-paclitaxel refractory ovarian cancer. , 2003, Gynecologic oncology.

[81]  M. Morgan,et al.  Phase II study of oxaliplatin in platinum-resistant and refractory ovarian cancer: a gynecologic group study. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[82]  G. Mor,et al.  Phenoxodiol – an isoflavone analog – induces apoptosis in chemoresistant ovarian cancer cells , 2003, Oncogene.

[83]  P. Rose,et al.  A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study. , 2003, Gynecologic oncology.

[84]  George Coukos,et al.  Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. , 2003, The New England journal of medicine.

[85]  K. Darcy,et al.  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. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[86]  D. Bodurka,et al.  Phase II trial of irinotecan in patients with metastatic epithelial ovarian cancer or peritoneal cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[87]  Anil K Sood,et al.  Preoperative serum vascular endothelial growth factor levels: significance in ovarian cancer. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[88]  P. Kenemans,et al.  Cellular and humoral responses after multiple injections of unconjugated chimeric monoclonal antibody MOv18 in ovarian cancer patients: a pilot study , 2002, Journal of Cancer Research and Clinical Oncology.

[89]  Roy S Herbst,et al.  Monoclonal antibodies to target epidermal growth factor receptor–positive tumors , 2002, Cancer.

[90]  T. Bauknecht,et al.  Vaccination with autologous tumour antigen-pulsed dendritic cells in advanced gynaecological malignancies: clinical and immunological evaluation of a phase I trial , 2002, Cancer Immunology, Immunotherapy.

[91]  X. Ye,et al.  The experimental study of ovarian carcinoma vaccine modified by human B7-1 and IFN-&ggr; genes , 2002, International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.

[92]  P. Ruf,et al.  Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody. , 2001, Blood.

[93]  A. Jakobsen,et al.  Phase II study of vinorelbine in the treatment of platinum-resistant ovarian carcinoma. , 2001, Gynecologic oncology.

[94]  L. Kanz,et al.  Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. , 2000, Blood.

[95]  J. Hainsworth,et al.  Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[96]  S. Faivre,et al.  Oxaliplatin and paclitaxel combination in patients with platinum-pretreated ovarian carcinoma: an investigator-originated compassionate-use experience. , 1999, Annals of oncology : official journal of the European Society for Medical Oncology.

[97]  A. Lissoni,et al.  Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[98]  J A Blessing,et al.  Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[99]  P. Kenemans,et al.  Escalating protein doses of chimeric monoclonal antibody MOv18 immunoglobulin G in ovarian carcinoma patients: A phase I study , 1997, Cancer.

[100]  R M Schultz,et al.  LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. , 1997, Cancer research.

[101]  L J Liang,et al.  Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[102]  J. Niloff,et al.  Strong expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in ovarian borderline and malignant neoplasms. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[103]  M. Préfontaine,et al.  Treatment of refractory ovarian cancer with 5-fluorouracil and leucovorin. , 1996, Gynecologic oncology.

[104]  J. Thigpen,et al.  Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[105]  S. Han,et al.  Synergistic embryotoxicity of combination pyrimethamine and folic acid in rats. , 1993, Reproductive toxicology.

[106]  A. Maraveyas,et al.  Asbestos fibers in the colonic wall. , 1974, British Journal of Cancer.

[107]  E. Gilboa,et al.  Regression of bladder tumors in mice treated with interleukin 2 gene- modified tumor cells [published erratum appears in J Exp Med 1993 Jun 1;177(6):following 1831] , 1993, The Journal of experimental medicine.

[108]  L R Coney,et al.  Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues. , 1992, Cancer research.

[109]  S. Rubin,et al.  Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[110]  Kenichi Tanaka,et al.  Use of adoptive transfer of tumor-infiltrating lymphocytes alone or in combination with cisplatin-containing chemotherapy in patients with epithelial ovarian cancer. , 1991, Cancer research.

[111]  W Godolphin,et al.  Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. , 1989, Science.

[112]  J. Thigpen.  Clinical Activity of Gemcitabine Plus Pertuzumab in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer , 2011 .

[113]  W. E. Richards,et al.  Phase II clinical trial of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant ovarian or primary peritoneal cancer: a gynecologic oncology group study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[114]  S. Groshen,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. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[115]  A. Rivkin,et al.  Panitumumab: human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal cancer. , 2008, Clinical therapeutics.

[116]  B. Foley,et al.  Preclinical evaluation of MORAb-003, a humanized monoclonal antibody antagonizing folate receptor-alpha. , 2007, Cancer immunity.

[117]  S. Keam,et al.  Trabectedin , 2012, Drugs.

[118]  P Maisonneuve,et al.  Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. , 2006, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[119]  Alessandro Lugli,et al.  Frequent EpCam protein expression in human carcinomas. , 2004, Human pathology.

[120]  T. Herzog.  Recurrent Ovarian Cancer: How Important Is It to Treat to Disease Progression? , 2004 .

[121]  A. D’Andrea,et al.  The Fanconi anaemia/BRCA pathway , 2003, Nature Reviews Cancer.

[122]  A. Berchuck,et al.  Weekly low-dose carboplatin and paclitaxel in the treatment of recurrent ovarian and peritoneal cancer. , 2003, Gynecologic oncology.

[123]  C. Williams.  Tamoxifen for relapse of ovarian cancer. , 2001, The Cochrane database of systematic reviews.

[124]  A. Gadducci,et al.  Serum CA125 assay at the time of relapse has no prognostic relevance in patients undergoing chemotherapy for recurrent ovarian cancer: a multicenter Italian study. , 1997, International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.

[125]  M. McKay,et al.  Cancer of the ovary. , 1994, The New England journal of medicine.

[126]  P. Layde,et al.  Oral contraceptive use and the risk of ovarian cancer. The Centers for Disease Control Cancer and Steroid Hormone Study. , 1983, JAMA.

[127]  C A SALVATORE,et al.  [Carcinoma of the ovary]. , 1960, Anais brasileiros de ginecologia.