Authors
Department of Obstetrics and Gynecology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Background: Ovarian cancer is the second most common malignancy in women worldwide, causing many deaths each year. Chemotherapy is one of the most important therapeutic strategies that can increase the survival of these patients; however, one of the problems in chemotherapy is resistance against platinum treatment. Evaluating the effect of platinum- and non-platinum-based chemotherapy in patients with recurrent platinum-resistant ovarian cancer can enhance our view on this issue.
Methods: The present review article sought to identify the treating efficacy of platinum and non-platinum-based chemotherapy in patients with recurrent platinum-resistant ovarian cancer by searching scientific databases and examining the aspects of platinum resistance in various articles. Results: Oncological results have shown that ovarian cancer is a deadly disease, and most cases are diagnosed when the cancer spreads outside the ovary and often throughout the entire abdomen. On the other hand, in many cases disease recurrence is associated with drug resistance. The use of a platinum-free interval has played an important role in its treatment efficacy. Understanding the cause of platinum resistance and discovering strategies to reduce drug resistance, especially to new ones, is very important.
Conclusion: The present article suggested oncology teams agree on treatment methods and the best treatment approach against platinum resistance in malignant ovarian cancers and offer a better treatment solution by considering innovative strategies.
Keywords
- 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA: a cancer journal for clinicians. 2015;65(1):5-29. 2. Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors. International journal of women's health. 2019;11:287-99. 3. Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, et al. Ovarian cancer statistics, 2018. CA: a cancer journal for clinicians. 2018;68(4):284-96. 4. Lowe KA, Chia VM, Taylor A, O'Malley C, Kelsh M, Mohamed M, et al. An international assessment of ovarian cancer incidence and mortality. Gynecologic oncology. 2013;130(1):107-14. 5. Kurman RJ. Origin and molecular pathogenesis of ovarian high-grade serous carcinoma. Annals of oncology : official journal of the European Society for Medical Oncology. 2013;24 Suppl 10:x16-21. 6. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2018;68(6):394-424. 7. Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ, 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2006;24(29):4699-707. 8. Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, et al. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet (London, England). 2003;361(9375):2099-106. 9. Pignata S, Scambia G, Bologna A, Signoriello S, Vergote IB, Wagner U, et al. Randomized Controlled Trial Testing the Efficacy of Platinum-Free Interval Prolongation in Advanced Ovarian Cancer: The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2017;35(29):3347-53. 10. Li QQ, Lee RX, Liang H, Wang G, Li JM, Zhong Y, et al. β-Elemene enhances susceptibility to cisplatin in resistant ovarian carcinoma cells via downregulation of ERCC-1 and XIAP and inactivation of JNK. International journal of oncology. 2013;43(3):721-8. 11. Pfisterer J, Ledermann JA. Management of platinum-sensitive recurrent ovarian cancer. Seminars in oncology. 2006;33(2 Suppl 6):S12-6. 12. Braicu EI, Sehouli J, Richter R, Pietzner K, Denkert C, Fotopoulou C. Role of histological type on surgical outcome and survival following radical primary tumour debulking of epithelial ovarian, fallopian tube and peritoneal cancers. British journal of cancer. 2011;105(12):1818-24. 13. Gilks CB, Ionescu DN, Kalloger SE, Köbel M, Irving J, Clarke B, et al. Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Human pathology. 2008;39(8):1239-51. 14. Storey DJ, Rush R, Stewart M, Rye T, Al-Nafussi A, Williams AR, et al. Endometrioid epithelial ovarian cancer : 20 years of prospectively collected data from a single center. Cancer. 2008;112(10):2211-20. 15. Seidman JD, Horkayne-Szakaly I, Haiba M, Boice CR, Kurman RJ, Ronnett BM. The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists. 2004;23(1):41-4. 16. Jenison EL, Montag AG, Griffiths CT, Welch WR, Lavin PT, Greer J, et al. Clear cell adenocarcinoma of the ovary: a clinical analysis and comparison with serous carcinoma. Gynecologic oncology. 1989;32(1):65-71. 17. Kurian AW, Hughes E, Handorf EA, Gutin A, Allen B, Hartman A-R, et al. Breast and ovarian cancer penetrance estimates derived from germline multiple-gene sequencing results in women. JCO Precision Oncology. 2017;1:1-12. 18. Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. Jama. 2017;317(23):2402-16. 19. Soliman PT, Slomovitz BM, Broaddus RR, Sun CC, Oh JC, Eifel PJ, et al. Synchronous primary cancers of the endometrium and ovary: a single institution review of 84 cases. Gynecologic oncology. 2004;94(2):456-62. 20. Zaino R, Whitney C, Brady MF, DeGeest K, Burger RA, Buller RE. Simultaneously detected endometrial and ovarian carcinomas--a prospective clinicopathologic study of 74 cases: a gynecologic oncology group study. Gynecologic oncology. 2001;83(2):355-62. 21. McConechy MK, Ding J, Senz J, Yang W, Melnyk N, Tone AA, et al. Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2014;27(1):128-34. 22. Veras E, Mao TL, Ayhan A, Ueda S, Lai H, Hayran M, et al. Cystic and adenofibromatous clear cell carcinomas of the ovary: distinctive tumors that differ in their pathogenesis and behavior: a clinicopathologic analysis of 122 cases. The American journal of surgical pathology. 2009;33(6):844-53. 23. Jones S, Wang TL, Shih Ie M, Mao TL, Nakayama K, Roden R, et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science (New York, NY). 2010;330(6001):228-31. 24. Matsumoto T, Yamazaki M, Takahashi H, Kajita S, Suzuki E, Tsuruta T, et al. Distinct β-catenin and PIK3CA mutation profiles in endometriosis-associated ovarian endometrioid and clear cell carcinomas. American journal of clinical pathology. 2015;144(3):452-63. 25. Cho KR, Shih Ie M. Ovarian cancer. Annual review of pathology. 2009;4:287-313. 26. Bodurka DC, Deavers MT, Tian C, Sun CC, Malpica A, Coleman RL, et al. Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study. Cancer. 2012;118(12):3087-94. 27. Malpica A, Deavers MT, Lu K, Bodurka DC, Atkinson EN, Gershenson DM, et al. Grading ovarian serous carcinoma using a two-tier system. The American journal of surgical pathology. 2004;28(4):496-504. 28. Gershenson DM, Bodurka DC, Lu KH, Nathan LC, Milojevic L, Wong KK, et al. Impact of Age and Primary Disease Site on Outcome in Women With Low-Grade Serous Carcinoma of the Ovary or Peritoneum: Results of a Large Single-Institution Registry of a Rare Tumor. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015;33(24):2675-82. 29. Gourley C, Farley J, Provencher DM, Pignata S, Mileshkin L, Harter P, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for ovarian and primary peritoneal low-grade serous carcinomas. International Journal of Gynecologic Cancer. 2014;24(Supp 3). 30. Vang R, Shih Ie M, Kurman RJ. Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems. Advances in anatomic pathology. 2009;16(5):267-82. 31. Dehari R, Kurman RJ, Logani S, Shih Ie M. The development of high-grade serous carcinoma from atypical proliferative (borderline) serous tumors and low-grade micropapillary serous carcinoma: a morphologic and molecular genetic analysis. The American journal of surgical pathology. 2007;31(7):1007-12. 32. Parker RL, Clement PB, Chercover DJ, Sornarajah T, Gilks CB. Early recurrence of ovarian serous borderline tumor as high-grade carcinoma: a report of two cases. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists. 2004;23(3):265-72. 33. Silva EG, Tornos CS, Malpica A, Gershenson DM. Ovarian serous neoplasms of low malignant potential associated with focal areas of serous carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 1997;10(7):663-7. 34. AGO-OVAR. Trials. https://gciggroup.com/system/files/2016%20Oct%20AGO%20slides%20OV.pdf. Accessed 1 July 2020. . 35. Ledermann JA, Luvero D, Shafer A, O'Connor D, Mangili G, Friedlander M, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for mucinous ovarian carcinoma. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2014;24(9 Suppl 3):S14-9. 36. Zaino RJ, Brady MF, Lele SM, Michael H, Greer B, Bookman MA. Advanced stage mucinous adenocarcinoma of the ovary is both rare and highly lethal: a Gynecologic Oncology Group study. Cancer. 2011;117(3):554-62. 37. Lee KR, Young RH. The distinction between primary and metastatic mucinous carcinomas of the ovary: gross and histologic findings in 50 cases. The American journal of surgical pathology. 2003;27(3):281-92. 38. Riopel MA, Ronnett BM, Kurman RJ. Evaluation of diagnostic criteria and behavior of ovarian intestinal-type mucinous tumors: atypical proliferative (borderline) tumors and intraepithelial, microinvasive, invasive, and metastatic carcinomas. The American journal of surgical pathology. 1999;23(6):617-35. 39. Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer: a review. Cancer biology & medicine. 2017;14(1):9-32. 40. Kumar S, Mahdi H, Bryant C, Shah JP, Garg G, Munkarah A. Clinical trials and progress with paclitaxel in ovarian cancer. International journal of women's health. 2010;2:411-27. 41. Yin J, Yan X, Yao X, Zhang Y, Shan Y, Mao N, et al. Secretion of annexin A3 from ovarian cancer cells and its association with platinum resistance in ovarian cancer patients. Journal of cellular and molecular medicine. 2012;16(2):337-48. 42. Pinato DJ, Graham J, Gabra H, Sharma R. Evolving concepts in the management of drug resistant ovarian cancer: dose dense chemotherapy and the reversal of clinical platinum resistance. Cancer treatment reviews. 2013;39(2):153-60. 43. Zhou K, Wang L, Cheng R, Liu X, Mao S, Yan Y. Elemene Increases Autophagic Apoptosis and Drug Sensitivity in Human Cisplatin (DDP)-Resistant Lung Cancer Cell Line SPC-A-1/DDP By Inducing Beclin-1 Expression. Oncology research. 2017. 44. Monk BJ, Coleman RL. Changing the paradigm in the treatment of platinum-sensitive recurrent ovarian cancer: from platinum doublets to nonplatinum doublets and adding antiangiogenesis compounds. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2009;19 Suppl 2:S63-7. 45. Mikuła-Pietrasik J, Witucka A, Pakuła M, Uruski P, Begier-Krasińska B, Niklas A, et al. Comprehensive review on how platinum- and taxane-based chemotherapy of ovarian cancer affects biology of normal cells. Cellular and molecular life sciences : CMLS. 2019;76(4):681-97. 46. Gao Y, Li Y, Zhang C, Han J, Liang H, Zhang K, et al. Evaluating the benefits of neoadjuvant chemotherapy for advanced epithelial ovarian cancer: a retrospective study. Journal of ovarian research. 2019;12(1):85. 47. Amable L. Cisplatin resistance and opportunities for precision medicine. Pharmacological research. 2016;106:27-36. 48. Weiner-Gorzel K, Dempsey E, Milewska M, McGoldrick A, Toh V, Walsh A, et al. Overexpression of the microRNA miR-433 promotes resistance to paclitaxel through the induction of cellular senescence in ovarian cancer cells. Cancer medicine. 2015;4(5):745-58. 49. Ishida S, McCormick F, Smith-McCune K, Hanahan D. Enhancing tumor-specific uptake of the anticancer drug cisplatin with a copper chelator. Cancer cell. 2010;17(6):574-83. 50. Li T, Peng J, Zeng F, Zhang K, Liu J, Li X, et al. Association between polymorphisms in CTR1, CTR2, ATP7A, and ATP7B and platinum resistance in epithelial ovarian cancer. International journal of clinical pharmacology and therapeutics. 2017;55(10):774-80. 51. Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. Journal of clinical oncology. 2001;19(14):3312-22. 52. Gordon AN, Tonda M, Sun S, Rackoff W. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecologic oncology. 2004;95(1):1-8. 53. Oronsky B, Ray CM, Spira AI, Trepel JB, Carter CA, Cottrill HM. A brief review of the management of platinum-resistant-platinum-refractory ovarian cancer. Medical oncology (Northwood, London, England). 2017;34(6):103. 54. Luo Y, Lee M, Kim HS, Chung HH, Song YS. Effect of neoadjuvant chemotherapy on platinum resistance in stage IIIC and IV epithelial ovarian cancer. Medicine. 2016;95(36):e4797. 55. Petrillo M, Ferrandina G, Fagotti A, Vizzielli G, Margariti PA, Pedone AL, et al. Timing and pattern of recurrence in ovarian cancer patients with high tumor dissemination treated with primary debulking surgery versus neoadjuvant chemotherapy. Annals of surgical oncology. 2013;20(12):3955-60. 56. da Costa AA, Valadares CV, Baiocchi G, Mantoan H, Saito A, Sanches S, et al. Neoadjuvant Chemotherapy Followed by Interval Debulking Surgery and the Risk of Platinum Resistance in Epithelial Ovarian Cancer. Annals of surgical oncology. 2015;22 Suppl 3:S971-8. 57. Gadducci A, Cosio S, Zizioli V, Notaro S, Tana R, Panattoni A, et al. Patterns of Recurrence and Clinical Outcome of Patients With Stage IIIC to Stage IV Epithelial Ovarian Cancer in Complete Response After Primary Debulking Surgery Plus Chemotherapy or Neoadjuvant Chemotherapy Followed by Interval Debulking Surgery: An Italian Multicenter Retrospective Study. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2017;27(1):28-36. 58. Sessa C, Cresta S, Noberasco C, Capri G, Gallerani E, De Braud F, et al. Phase I clinical and pharmacokinetic study of trabectedin and cisplatin in solid tumours. European journal of cancer (Oxford, England : 1990). 2009;45(12):2116-22. 59. Krasner CN, McMeekin DS, Chan S, Braly PS, Renshaw FG, Kaye S, et al. A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. British journal of cancer. 2007;97(12):1618-24. 60. Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, et al. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010;28(19):3107-14. 61. Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, et al. Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: overall survival analysis. European journal of cancer (Oxford, England : 1990). 2012;48(15):2361-8. 62. Ferrandina G, Salutari V, Vincenzi B, Marinaccio M, Naglieri E, Loizzi V, et al. Trabectedin as single agent in the salvage treatment of heavily treated ovarian cancer patients: a retrospective, multicenter study. Gynecologic oncology. 2013;130(3):505-10. 63. del Campo JM, Sessa C, Krasner CN, Vermorken JB, Colombo N, Kaye S, et al. Trabectedin as single agent in relapsed advanced ovarian cancer: results from a retrospective pooled analysis of three phase II trials. Medical oncology (Northwood, London, England). 2013;30(1):435. 64. Del Campo JM, Roszak A, Bidzinski M, Ciuleanu TE, Hogberg T, Wojtukiewicz MZ, et al. Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer. Annals of oncology : official journal of the European Society for Medical Oncology. 2009;20(11):1794-802. 65. Nicoletto MO, Baldoni A, Casarin A, Randon G, Nardin M, Baretta Z, et al. Trabectedin plus pegylated liposomal doxorubicin: retrospective analysis in heavily pretreated platinum-sensitive ovarian cancer. Tumori. 2015;101(5):506-10. 66. Pignata S, Scambia G, Raspagliesi F, Murgia V, Pisano C, Salutari V, et al. The MITO8 phase III international multicenter randomized study testing the effect on survival of prolonging platinum-free interval (PFI) in patients with ovarian cancer (OC) recurring between 6 and 12 months after previous platinum-based chemotherapy: A collaboration of MITO, MANGO, AGO, BGOG, ENGOT, and GCIG. American Society of Clinical Oncology; 2016. 67. Hamanishi J, Mandai M, Konishi I. Immune checkpoint inhibition in ovarian cancer. International immunology. 2016;28(7):339-48. 68. Colmegna B, Uboldi S, Frapolli R, Licandro SA, Panini N, Galmarini CM, et al. Increased sensitivity to platinum drugs of cancer cells with acquired resistance to trabectedin. British journal of cancer. 2015;113(12):1687-93. 69. Poveda A, Vergote I, Tjulandin S, Kong B, Roy M, Chan S, et al. Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III randomized trial. Annals of oncology : official journal of the European Society for Medical Oncology. 2011;22(1):39-48. 70. Poveda A, Ray-Coquard I, Romero I, Lopez-Guerrero JA, Colombo N. Emerging treatment strategies in recurrent platinum-sensitive ovarian cancer: focus on trabectedin. Cancer treatment reviews. 2014;40(3):366-75. 71. Kato MK, Yunokawa M, Bun S, Shimoi T, Yonemori K, Miyasaka N, et al. Treatment strategies for recurrent ovarian cancer in older adult patients in Japan: a study based on real-world data. Journal of cancer research and clinical oncology. 2020;146(5):1335-41. 72. Piccart MJ, Green JA, Lacave AJ, Reed N, Vergote I, Benedetti-Panici P, et al. Oxaliplatin or paclitaxel in patients with platinum-pretreated advanced ovarian cancer: A randomized phase II study of the European Organization for Research and Treatment of Cancer Gynecology Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000;18(6):1193-202. 73. Buda A, Floriani I, Rossi R, Colombo N, Torri V, Conte PF, et al. Randomised controlled trial comparing single agent paclitaxel vs epidoxorubicin plus paclitaxel in patients with advanced ovarian cancer in early progression after platinum-based chemotherapy: an Italian Collaborative Study from the Mario Negri Institute, Milan, G.O.N.O. (Gruppo Oncologico Nord Ovest) group and I.O.R. (Istituto Oncologico Romagnolo) group. British journal of cancer. 2004;90(11):2112-7. 74. Cantù MG, Buda A, Parma G, Rossi R, Floriani I, Bonazzi C, et al. Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2002;20(5):1232-7. 75. Kishimoto S, Yasuda M, Fukushima S. Changes in the Expression of Various Transporters as Influencing Factors of Resistance to Cisplatin. Anticancer research. 2017;37(10):5477-84. 76. Öhrvik H, Nose Y, Wood LK, Kim BE, Gleber SC, Ralle M, et al. Ctr2 regulates biogenesis of a cleaved form of mammalian Ctr1 metal transporter lacking the copper- and cisplatin-binding ecto-domain. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(46):E4279-88. 77. Sørensen BH, Dam CS, Stürup S, Lambert IH. Dual role of LRRC8A-containing transporters on cisplatin resistance in human ovarian cancer cells. Journal of inorganic biochemistry. 2016;160:287-95. 78. Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nature reviews Cancer. 2004;4(6):423-36. 79. Rosenberg P, Andersson H, Boman K, Ridderheim M, Sorbe B, Puistola U, et al. Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum. Acta oncologica (Stockholm, Sweden). 2002;41(5):418-24. 80. Colombo N, Kutarska E, Dimopoulos M, Bae DS, Rzepka-Gorska I, Bidzinski M, et al. Randomized, open-label, phase III study comparing patupilone (EPO906) with pegylated liposomal doxorubicin in platinum-refractory or -resistant patients with recurrent epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30(31):3841-7. 81. Rustin GJ, Vergote I, Eisenhauer E, Pujade-Lauraine E, Quinn M, Thigpen T, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2011;21(2):419-23. 82. Vergote I, Calvert H, Kania M, Kaiser C, Zimmermann AH, Sehouli J. A randomised, double-blind, phase II study of two doses of pemetrexed in the treatment of platinum-resistant, epithelial ovarian or primary peritoneal cancer. European journal of cancer (Oxford, England : 1990). 2009;45(8):1415-23. 83. Gore ME, Fryatt I, Wiltshaw E, Dawson T. Treatment of relapsed carcinoma of the ovary with cisplatin or carboplatin following initial treatment with these compounds. Gynecologic oncology. 1990;36(2):207-11. 84. National Academies of Sciences E, Medicine. Ovarian cancers: evolving paradigms in research and care: National Academies Press; 2016.