JCT  Vol.5 No.13 , November 2014
Current Possible Drug Therapies for Ovarian Cancer
Abstract: Ovarian cancer is the most aggressive gynecologic cancer of the heterogenous phenotypes. Development of the new chemotherapeutic agents and drug delivery mode makes better outcomes for patient treatments. Optimal cytoreductive therapy followed by molecular targeting therapy, intraperitoneal chemotherapy and dose dense chemotherapy is a hot therapeutic concept in ovarian cancers. In our review, we will introduce recent therapeutic advances in epithelial ovarian cancer patients.
Cite this paper: Seoung, J. , Park, Y. , Rhim, C. and Kim, S. (2014) Current Possible Drug Therapies for Ovarian Cancer. Journal of Cancer Therapy, 5, 1203-1214. doi: 10.4236/jct.2014.513122.

[1]   Siegel, R., Naishadham, D. and Jemal, A. (2013) Cancer Statistics, 2013. CA: A Cancer Journal for Clinicians, 63, 11-30.

[2]   Norton, L. (2001) Theoretical Concepts and the Emerging Role of Taxanes in Adjuvant Therapy. The Oncologist, 6, 30-35.

[3]   Katsumata, N., Yasuda, M., Takahashi, F., Isonishi, S., Jobo, T., Aoki, D., et al. (2009) Dose-Dense Paclitaxel Once a Week in Combination with Carboplatin Every 3 Weeks for Advanced Ovarian Cancer: A Phase 3, Open-Label, Randomised Controlled Trial. Lancet, 374, 1331-1338.

[4]   Katsumata, N., Yasuda, M., Isonishi, S., Takahashi, F., Michimae, H., Kimura, E., et al. (2013) Long-Term Results of Dose-Dense Paclitaxel and Carboplatin versus Conventional Paclitaxel and Carboplatin for Treatment of Advanced Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (JGOG 3016): A Randomised, Controlled, Open-Label Trial. The Lancet Oncology, 14, 1020-1026.

[5]   Pignata, S., Scambia, G., Katsaros, D., Gallo, C., Pujade-Lauraine, E., De Placido, S., et al. (2014) Carboplatin plus Paclitaxel Once a Week versus Every 3 Weeks in Patients with Advanced Ovarian Cancer (MITO-7): A Randomised, Multicentre, Open-Label, Phase 3 Trial. The Lancet Oncology, 15, 396-405.

[6]   Ozols, R.F. (2005) Treatment Goals in Ovarian Cancer. International Journal of Gynecological Cancer: Official Journal of the International Gynecological Cancer Society, 15, 3-11.

[7]   Kitayama, J. (2014) Intraperitoneal Chemotherapy against Peritoneal Carcinomatosis: Current Status and Future Perspective. Surgical Oncology, 23, 99-106.

[8]   Armstrong, D.K., Bundy, B., Wenzel, L., Huang, H.Q., Baergen, R., Lele, S., et al. (2006) Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer. The New England Journal of Medicine, 354, 34-43.

[9]   Morgan Jr., R.J., Alvarez, R.D., Armstrong, D.K., Boston, B., Burger, R.A., Chen, L.M., et al. (2011) Epithelial Ovarian Cancer. Journal of the National Comprehensive Cancer Network, 9, 82-113.

[10]   Welfare Aloha. Australian Cancer Incidence and Mortality (ACIM) Books.

[11]   Jaaback, K., Johnson, N. and Lawrie, T.A. (2011) Intraperitoneal Chemotherapy for the Initial Management of Primary Epithelial Ovarian Cancer. The Cochrane Database of Systematic Reviews, 2011, Article ID: CD005340.

[12]   Markman, M. (2009) An Update on the Use of Intraperitoneal Chemotherapy in the Management of Ovarian Cancer. Cancer Journal, 15, 105-109.

[13]   Barlin, J.N., Dao, F., Zgheib, N.B., Ferguson, S.E., Sabbatini, P.J., Hensley, M.L., et al. (2012) Progression-Free and Overall Survival of a Modified Outpatient Regimen of Primary Intravenous/Intraperitoneal Paclitaxel and Intraperitoneal Cisplatin in Ovarian, Fallopian Tube and Primary Peritoneal Cancer. Gynecologic Oncology, 125, 621-624.

[14]   Blinman, P., Gainford, C., Donoghoe, M., Martyn, J., Blomfield, P., Grant, P., et al. (2013) Feasibility, Acceptability and Preferences for Intraperitoneal Chemotherapy with Paclitaxel and Cisplatin after Optimal Debulking Surgery for Ovarian and Related Cancers: An ANZGOG Study. Journal of Gynecologic Oncology, 24, 359-366.

[15]   Matsumura, Y. and Maeda, H. (1986) A New Concept for Macromolecular Therapeutics in Cancer Chemotherapy: Mechanism of Tumoritropic Accumulation of Proteins and the Antitumor Agent Smancs. Cancer Research, 46, 6387-6392.

[16]   Bokemeyer, C. (2010) Catumaxomab—Trifunctional Anti-EpCAM Antibody Used to Treat Malignant Ascites. Expert Opinion on Biological Therapy, 10, 1259-1269.

[17]   Wimberger, P., Gilet, H., Gonschior, A.K., Heiss, M.M., Moehler, M., Oskay-Oezcelik, G., et al. (2012) Deterioration in Quality of Life (QoL) in Patients with Malignant Ascites: Results from a Phase II/III Study Comparing Paracentesis plus Catumaxomab with Paracentesis Alone. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 23, 1979-1985.

[18]   Eskander, R.N. and Randall, L.M. (2011) Bevacizumab in the Treatment of Ovarian Cancer. Biologics: Targets & Therapy, 5, 1-5.

[19]   Folkman, J. (1971) Tumor Angiogenesis: Therapeutic Implications. The New England Journal of Medicine, 285, 1182-1186.

[20]   Burger, R.A., Brady, M.F., Bookman, M.A., Fleming, G.F., Monk, B.J., Huang, H., et al. (2011) Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer. The New England Journal of Medicine, 365, 2473-2483.

[21]   Perren, T.J., Swart, A.M., Pfisterer, J., Ledermann, J.A., Pujade-Lauraine, E., Kristensen, G., et al. (2011) A Phase 3 Trial of Bevacizumab in Ovarian Cancer. The New England Journal of Medicine, 365, 2484-2496.

[22]   Wagner, U., Marth, C., Largillier, R., Kaern, J., Brown, C., Heywood, M., et al. (2012) Final Overall Survival Results of Phase III GCIG CALYPSO Trial of Pegylated Liposomal Doxorubicin and Carboplatin vs Paclitaxel and Carboplatin in Platinum-Sensitive Ovarian Cancer Patients. British Journal of Cancer, 107, 588-591.

[23]   Aghajanian, C., Blank, S.V., Goff, B.A., Judson, P.L., Teneriello, M.G., Husain, A., et al. (2012) OCEANS: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Chemotherapy with or without Bevacizumab in Patients with Platinum-Sensitive Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 30, 2039-2045.

[24]   Pujade-Lauraine, E., Hilpert, F., Weber, B., Reuss, A., Poveda, A., Kristensen, G., et al. (2014) Bevacizumab Combined with Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, Published Online.

[25]   Du Bois, A., Floquet, A., Kim, J.W., Rau, J., Maria Del Campo, J., Friedlander, M., Pignata, S., et al. (2013) Randomized, Double-Blind, Phase III Trial of Pazopanib versus Placebo in Women Who Have Not Progressed after First-Line Chemotherapy for Advanced Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (AEOC): Results of an International Intergroup Trial (AGO-OVAR16). Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 31, Article ID: LBA5503.

[26]   Matulonis, U.A., Berlin, S., Ivy, P., Tyburski, K., Krasner, C., Zarwan, C., et al. (2009) Cediranib, an Oral Inhibitor of Vascular Endothelial Growth Factor Receptor Kinases, Is an Active Drug in Recurrent Epithelial Ovarian, Fallopian Tube and Peritoneal Cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 27, 5601-5606.

[27]   Monk, B.J., Poveda, A., Vergote, I., Raspagliesi, F., Fujiwara, K., Bae, D.S. and Oaknin, A. (2013) A Phase III, Randomized, Double-Blind Trial of Weekly Paclitaxel plus the Angiopoietin 1 and 2 Inhibitor, Trebananib or Placebo in Women with Recurrent Ovarian Cancer: TRINOVA-1. European Journal of Cancer, 49.

[28]   DuBois, A., Kristensen, G., Ray-Coquard, I., Reuss, A., Pignata, S., Colombo, N. and Denison, U. (2013) AGO-OVAR 12: A Randomized Placebo-Controlled GCIG/ENGOT-Intergroup Phase III Trial of Standard Frontline Chemotherapy +/? Nintedanib for Advanced Ovarian Cancer. International Journal of Gynecological Cancer: Official Journal of the International Gynecological Cancer Society, 23, Oral Abstract.

[29]   Liu, J.F., Konstantinopoulos, P.A. and Matulonis, U.A. (2014) PARP Inhibitors in Ovarian Cancer: Current Status and Future Promise. Gynecologic Oncology, 133, 362-369.

[30]   Weberpals, J.I., Clark-Knowles, K.V. and Vanderhyden, B.C. (2008) Sporadic Epithelial Ovarian Cancer: Clinical Relevance of BRCA1 Inhibition in the DNA Damage and Repair Pathway. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 26, 3259-3267.

[31]   Audeh, M.W., Carmichael, J., Penson, R.T., Friedlander, M., Powell, B., Bell-McGuinn, K.M., et al. (2010) Oral Poly(ADP-ribose) Polymerase Inhibitor Olaparib in Patients with BRCA1 or BRCA2 Mutations and Recurrent Ovarian Cancer: A Proof-of-Concept Trial. The Lancet, 376, 245-251.

[32]   Gelmon, K.A., Tischkowitz, M., Mackay, H., Swenerton, K., Robidoux, A., Tonkin, K., et al. (2011) Olaparib in Patients with Recurrent High-Grade Serous or Poorly Differentiated Ovarian Carcinoma or Triple-Negative Breast Cancer: A Phase 2, Multicentre, Open-Label, Non-Randomised Study. The Lancet Oncology, 12, 852-861.

[33]   Kaye, S.B., Lubinski, J., Matulonis, U., Ang, J.E., Gourley, C., Karlan, B.Y., et al. (2012) Phase II, Open-Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of Olaparib, a Poly(ADP-Ribose) Polymerase Inhibitor, and Pegylated Liposomal Doxorubicin in Patients with BRCA1 or BRCA2 Mutations and Recurrent Ovarian Cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 30, 372-379.

[34]   Ledermann, J., Harter, P., Gourley, C., Friedlander, M., Vergote, I., Rustin, G., et al. (2012) Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer. The New England Journal of Medicine, 366, 1382-1392.

[35]   Kummar, S., Ji, J., Morgan, R., Lenz, H.J., Puhalla, S.L., Belani, C.P., et al. (2012) A Phase I Study of Veliparib in Combination with Metronomic Cyclophosphamide in Adults with Refractory Solid Tumors and Lymphomas. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 18, 1726-1734.

[36]   Coleman, R.L., Sill, M. and Aghajanian, C. (2013) A Phase II Evaluation of the Potent, Highly Selective PARP Inhibitor Veliparib in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Patients Who Carry a Germline BRCA1 or BRCA2 Mutation—A Gynecologic Oncology Group Study. Proceedings of Society of Gynecologic Oncology 45th Annual Meeting on Women’s Cancer, Tampa, 22-25 March 2014, Abstract 136.

[37]   Jones, P., Altamura, S., Boueres, J., Ferrigno, F., Fonsi, M., Giomini, C., et al. (2009) Discovery of 2-{4-[(3S)-Piperidin-3-yl]Phenyl}-2H-Indazole-7-Carboxamide (MK-4827): A Novel Oral Poly(ADP-Ribose)Polymerase (PARP) Inhibitor Efficacious in BRCA-1 and -2 Mutant Tumors. Journal of Medicinal Chemistry, 52, 7170-7185.

[38]   Sandhu, S.K., Schelman, W.R., Wilding, G., Moreno, V., Baird, R.D., Miranda, S., et al. (2013) The Poly(ADP-Ribose) Polymerase Inhibitor Niraparib (MK4827) in BRCA Mutation Carriers and Patients with Sporadic Cancer: A Phase 1 Dose-Escalation Trial. The Lancet Oncology, 14, 882-892.

[39]   Kristeleit, R.B.H., LoRusso, P., Patel, M., Giordano, H. and Evans, J. (2013) Phase I Study of Continuous Oral Rucaparib: Analysis of Patient Subgroup with Ovarian/Peritoneal Cancer. International Journal of Gynecological Cancer, 23, S564.

[40]   Gonzalez-Martin, A., Gladieff, L., Tholander, B., Stroyakovsky, D., Gore, M., Scambia, G., et al. (2013) Efficacy and Safety Results from OCTAVIA, a Single-Arm Phase II Study Evaluating Front-Line Bevacizumab, Carboplatin and Weekly Paclitaxel for Ovarian Cancer. European Journal of Cancer, 49, 3831-3838.

[41]   Dean, E., Middleton, M.R., Pwint, T., Swaisland, H., Carmichael, J., Goodege-Kunwar, P., et al. (2012) Phase I Study to Assess the Safety and Tolerability of Olaparib in Combination with Bevacizumab in Patients with Advanced Solid Tumors. British Journal of Cancer, 106, 468-474.

[42]   Cameron, E. and Pauling, L. (1976) Supplemental Ascorbate in the Supportive Treatment of Cancer: Prolongation of Survival Times in Terminal Human Cancer. Proceedings of the National Academy of Sciences of the United States of America, 73, 3685-3689.

[43]   Padayatty, S.J., Sun, A.Y., Chen, Q., Espey, M.G., Drisko, J. and Levine, M. (2010) Vitamin C: Intravenous Use by Complementary and Alternative Medicine Practitioners and Adverse Effects. PLoS ONE, 5, e11414.

[44]   Drisko, J.A., Chapman, J. and Hunter, V.J. (2003) The Use of Antioxidant Therapies during Chemotherapy. Gynecologic Oncology, 88, 434-439.

[45]   Prasad, K.N., Cole, W.C., Kumar, B. and Che Prasad, K. (2002) Pros and Cons of Antioxidant Use during Radiation Therapy. Cancer Treatment Reviews, 28, 79-91.

[46]   Frei, B. (1994) Reactive Oxygen Species and Antioxidant Vitamins: Mechanisms of Action. The American Journal of Medicine, 97, 5S-13S.

[47]   Nakayama, A., Alladin, K.P., Igbokwe, O. and White, J.D. (2011) Systematic Review: Generating Evidence-Based Guidelines on the Concurrent Use of Dietary Antioxidants and Chemotherapy or Radiotherapy. Cancer Investigation, 29, 655-667.

[48]   Lawenda, B.D., Kelly, K.M., Ladas, E.J., Sagar, S.M., Vickers, A. and Blumberg, J.B. (2008) Should Supplemental Antioxidant Administration Be Avoided during Chemotherapy and Radiation Therapy? Journal of the National Cancer Institute, 100, 773-783.

[49]   Thomson, C.A., Neuhouser, M.L., Shikany, J.M., Caan, B.J., Monk, B.J., Mossavar-Rahmani, Y., et al. (2008) The Role of Antioxidants and Vitamin A in Ovarian Cancer: Results from the Women’s Health Initiative. Nutrition and Cancer, 60, 710-719.

[50]   Harris, H.R., Orsini, N. and Wolk, A. (2014) Vitamin C and Survival among Women with Breast Cancer: A Meta-Analysis. European Journal of Cancer, 50, 1223-1231.

[51]   Vance, T.M., Su, J., Fontham, E.T., Koo, S.I. and Chun, O.K. (2013) Dietary Antioxidants and Prostate Cancer: A Review. Nutrition and Cancer, 65, 793-801.

[52]   Mamede, A.C., Pires, A.S., Abrantes, A.M., Tavares, S.D., Goncalves, A.C., Casalta-Lopes, J.E., et al. (2012) Cytotoxicity of Ascorbic Acid in a Human Colorectal Adenocarcinoma Cell Line (WiDr): In Vitro and in Vivo Studies. Nutrition and Cancer, 64, 1049-1057.

[53]   Chen, Q., Espey, M.G., Sun, A.Y., Lee, J.H., Krishna, M.C., Shacter, E., et al. (2007) Ascorbate in Pharmacologic Concentrations Selectively Generates Ascorbate Radical and Hydrogen Peroxide in Extracellular Fluid in Vivo. Proceedings of the National Academy of Sciences of the United States of America, 104, 8749-8754.

[54]   Cancer Genome Atlas Research Network (2011) Integrated Genomic Analyses of Ovarian Carcinoma. Nature, 474, 609-615.

[55]   Davidson, B., Trope, C.G. and Reich, R. (2014) The Clinical and Diagnostic Role of microRNAs in Ovarian Carcinoma. Gynecologic Oncology, 133, 640-646.