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DOI: https://doi.org/10.29296/25877313-2018-08-03
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S.V. Khokhlova Dr.Sc. (Med.), Chief Research Scientist, Chemotherapy Department, N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia (Moscow) E-mail: svkhokhlova@mail.ru D.N. Kushlinsky Ph.D. (Med.), Oncogynecologist, Department of Innovative Oncology and Gynecology, V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology of the Ministry of Health of Russia (Moscow)

Contemporary foreign and domestic publications concerning the issues of pharmacologic treatment of ovarian cancer patients are reviewed. In this section of the review different regimes of anti-angiogenic therapy, the key targets of anti-angiogenic drugs (VEGF, VEGFR1-3), their effectiveness and toxicity, application in various combinations with taxanes and platinum derivatives, the role of the CA-125 marker in assessing the effectiveness of treatment in patients ovarian cancer are described. Also the basic principles of relapses treatment in patients with ovarian cancer and the classification of relapses are presented. A special place is given to drug therapy of platinum-sensitive relapses of ovarian cancer

ovarian cancer
anti-angiogenic therapy
classification of relapses
platinum-sensitive relapses

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  1. Hohlova S.V. Novye tendentsii v lechenii rasprostra-nennogo raka jaichnikov // Opuholi zhenskoj reproduk-tivnoj sistemy. 2008, 4:64−72. (Xoxlova S.V. Novy`e tendencii v lechenii rasprostranen-nogo raka yaichnikov // Opuxoli zhenskoj reproduktivnoj sistemy`. 2008, 4:64−72. (In Russian)).
  2. Hohlova S.V. Rol' ingibitorov sosudistogo endoteli-al'nogo faktora rosta v lechenii raka jaichnikov // Opu-holi zhenskoj reproduktivnoj sistemy. 2010, 3:35−44. (Xoxlova S.V. Rol` ingibitorov sosudistogo e`ndoteli-al`nogo faktora rosta v lechenii raka yaichnikov // Opuxoli zhenskoj reproduktivnoj sistemy`. 2010, 3:35−44. (In Rus-sian)).
  3. Oza A.M., Perren T.J., Swart A.M., Schröder W., Pujade-Lauraine E., Havsteen H., Beale P., Cervantes A.M., Embleton A.C., Parmar M. ICON7: Final overall survival results in the GCIG phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer [abstract]. E. J. Cancer. 2013, 49(2):LBA:6.
  4. Burger R., Brady M., Bookman M., Monk B., Walker J., Homesley H., Fowler J., Greer B., Boente M., Liang S. Prospective investigation of risk factors for gastrointestinal adverse events in a phase III randomized trial of bevacizumab in first line therapy of advanced epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer: a Gynecologic Oncology Group study. Gynecol. Oncol. 2011, 120:S5.
  5. . Burger R.A., Brady M.F., Bookman M.A., Fleming G.F., Monk B.J., Huang H., Mannel R.S., Homesley H.D., Fowler J., Greer B.E., Boente M., Birrer M.J., Liang S.X. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N. Engl. J. Med. 2011a, 365(26):2473−2483.
  6. Pujade-Lauraine E., Oza A.M., Perren T.J., Swart A.M., Mahner S., Gourley C., Malander S., Parmar M. ICON7: final overall survival results in the GCIG phase III rando-mized trial of bevacizumab in women with newly diagnosed ovarian cancer. Eur. J. Cancer. 2013, 49(3):LBA6.
  7. Du Bois A., Floquet A., Kim J.W., Rau J., Del Campo J. M., Friedlander M., Pignata S., Fujiwara K., Vergote I., Colombo N., Mirza M.R., Monk B.J., Wimberger P., Ray-Coquard I., Zang R., Diaz-Padilla I., Baumann K.H., Kim J.H., Harter P. Randomized, double blind, phase III trial of pazopanib versus placebo in women who have progressed after first line chemotherapy for advanced epithelial ovarian,fallopian tube, or primary peritoneal cancer: results of an interna-tional Intergroup trial (AGO OVAR 16). J. Clin. Oncol. 2013;31(18):LBA5503.
  8. Hohlova S.V. Novyj vzgljad na lechenie raka jaichnikov // Opuholi zhenskoj reproduktivnoj sistemy. 2010, 1:68−71. (Xoxlova S.V. Novy`j vzglyad na lechenie raka yaichnikov // Opuxoli zhenskoj reproduktivnoj sistemy`. 2010, 1:68−71. (In Russian)).
  9. Rustin G.J., van der Burg M.E., Griffin C.L., Guthrie D., Lamont A., Jayson G.C., Kristensen G., Mediola C., Coens C., Qian W., Parmar M.K., Swart A.M. Early versus delayed treat-ment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial. Lancet. 2010, 376(9747):1155−1163.
  10. Skaznik-Wikiel M.E., Sukumvanich P., Beriwal S., Zorn K.K., Kelley J.L., Richard S.D., Krivak T.C. Possible use of CA 125 level normalization after the third chemotherapy cycle in deciding on chemotherapy regimen in patients with epithelial ovarian cancer: brief report. Int. J. Gynecol. Cancer. 2011, 21(6):1013−1017.
  11. Rustin G.J., Nelstrop A.E., McClean P. et al. Defining re-sponse of ovarian carcinoma to initial chemotherapy accord-ing to serum CA 125. J. Clin. Oncol. 1996, 14:1545–1551.
  12. Herzog T.J., Vermorken J.B., Pujade-Lauraine E., Pro-vencher D.M., Jagiello-Gruszfeld A., Kong B., Boman K., Park Y.C., Parekh T., Lebedinsky C., Gomez J., Monk B.J. Correlation between CA 125 serum level and response by RECIST in a phase III recurrent ovarian cancer study. Gynecol. Oncol. 2011, 122(2):350−355.
  13. . Sabbatini P., Mooney D., Iasonos A., et al. Early CA-125 fluc-tuations in patients with recurrent ovarian cancer receiving chemotherapy. Int J Gynecol Cancer. 2007, 17(3):589–594.
  14. Thigpen J.T., Blessing J.A., Ball H., Hummel S.J., Barrett R.J. Phase II trial of paclitaxel in with progressive ovarian carci-noma after platinum based chemotherapy: a Gynecologic Oncology Group study. J. Clin. Oncol. 1994, 12(9):1748−1753. 15. Armstrong D.K. Relapsed ovarian cancer: challenges and management strategies for a chronic disease. Oncologist. 2002, 7(5):20−28.
  15. Buda A., Floriani I., Rossi R., Colombo N., Torri V., Conte P.F., Fossati R., Ravaioli A, Mangioni C. Randomised cont-rolled trial comparing single agent paclitaxel vs. Epidoxo-rubicin plus paclitaxel in patients with advanced ovarian cancer in early progression after platinum based chemo-therapy: an Italian Collaborative Study from the Mario Negri Institute, Milan, G.O.NO. (Gruppo Oncologico Nord Ovest) group and I.O.R. (Istituto Oncologico Romagnolo) group. Br. J. Cancer. 2004, 90(11):2112−2127.
  16. Herzog T.J. The current treatment of recurrent ovarian can-cer. Curr. Oncol. Rep. 2006, 8(6):448−454.
  17. Markman M., Rothman R., Hakes T., Reichman B., Hoskins W., Rubin S., Jones W., Almadrones L., Lewis J.L. (Jr.) Second line platinum therapy in patients with ovarian cancer previ-ously treated with cisplatin. J. Clin. Oncol. 1991, 9(3):389−393.
  18. Gore M.E., Fryatt I., Wiltshaw E., Dawson T. Treatment of relapsed carcinoma of ovary with cisplatin or carboplatin following initial treatment with these compounds. Gynecol. Oncol. 1990, 36(2):207−211.
  19. Ushijima K. Treatment for Recurrent Ovarian cancer At First relapse. J. Oncol. 2010, 2010:497429.
  20. Bermejo M.A.A., Montes A.F., Lopez E.P., Viejo M.A.N., Gomez J.G., Mata J.G. The Role of Chemotherapy in Re-current Ovarian cancer. INTECH. 2013. Chapter 9.
  21. Monk B.J., Herzog T.J., Kaye S.B., Krasner C.N., Ver-morken J.B., Muggia F.M., Pujade-Lauraine E., Park Y.C., Parekh T.V., Poveda A.M. Trabectedin plus pegylated lipo-somal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: overall survival analysis. Eur. J. Cancer. 2012, 48(15):2361−2368.
  22. Eisenhauer E.A., Vermorken J.B., van Glabbeke M. Predictors of response to subsequent chemotherapy in platinum pretreated ovarian cancer: a multivariate analysis of 704 patients. Ann. Oncol. 1997, 8(10):963−968.
  23. Lee C.K., Simes R.J., Brown C., Lord S., Wagner U., Plante M., Vergote I., Pisano C., Parma G., Burges A., Bourgeois H., Högberg T., Bentley J., Angleitner-Boubenizek L., Ferrero A., Richter B., Hirte H., Gebski V., Pfisterer J., Pujade-Lauraine E., Friedlander M. Prognostic nomogram to predict progression free survival in patients with platinum sensitive recurrent ovarian cancer. Br. J. Cancer. 2011, 105(8):1144−1450.
  24. Gonzalez-Martin A.J., Calvo E., Bover I., Rubio M.J., Arcusa A., Casado A., Ojeda B., Balana C., Martinez E., Herrero A., Pardo B., Adrover E., Rifa J., Godes M.J., Moyano A., Cervantes A. Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum sensitive recurrent advanced ovarian carcinoma: a GEICO (GrupoEspanol de Investigacionen Cancer de Ovario) study. Ann. Oncol. 2005, 16(5):749−755.
  25. Hoskins P.J., Le N. Identifying patients unlikely to benefit from further chemotherapy: a descriptive study of outcome at each relapse in ovarian cancer. Gynecol. Oncol. 2005;97(3):862-869.
  26. Gordon A.N., Fleagle J.T., Guthrie D., Parkin D.E., Gore M.E., Lacave A.J. Recurrent epithelial ovarian carcinoma: a ran-domized phase III study of pegylated liposomal doxorubicin versus topotecan. J. Clin. Oncol. 2001, 19(14):3312−3322.
  27. Piccart M.J., Green J.A., Lacave A.J., Reed N., Vergote I., Benedetti-Panici P., Bonetti A., Kristeller-Tome V., Fernandez C.M., Curran D., Van Glabbeke M., Lacombe D., Pinel M.C., Pecorelli S. 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. J. Clin. Oncol. 2000, 18(6):1193−1202.
  28. Markman M., Markman J., Webster K., Zanotti K., Kulp B., Peterson G., Belinson J. Duration of response to second line, platinum based chemotherapy for ovarian cancer: implications for patient management and clinical trial design. J. Clin. Oncol. 2004, 22(15):3120−3125.
  29. Gronlund B., Hogdall C., Hansen H.H., Engelholm S.A. Results of reinduction therapy with paclitaxel and carbo-platin in recurrent epithelial ovarian cancer. Gynecol. Oncol. 2001, 83(1):128−134.
  30. Dizon D.S., Dupont J., Anderson S., Sabbatini P., Hummer A., Aghajanian C., Spriggs D. Treatment of recurrent ovarian cancer: a retrospective analysis of women treated with single agent carboplatin originally treated with carboplatin and paclitaxel. The Memorial Sloan Kettering Cancer Center experience. Gynecol. Oncol. 2003, 91(3):584−590.
  31. Cantu M.G., Buda A., Parma G., Rossi R., Floriani I., Bonazzi C., Dell'Anna T., Torri V., Colombo N. Randomized controlled trial of single agent paclitaxel versus cyclo-phosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first line platinum based regimens. J. Clin. Oncol. 2002, 20(5):1232−1237.
  32. Pfisterer J., Plante M., Vergote I., du Bois A., Hirte H., Lacave A.J., Wagner U., Stähle A., Stuart G., Kimmig R., Olbricht S., Le T., Emerich J., Kuhn W., Bentley J., Jackisch C., Luck H.J., Rochon J., Zimmermann A.H., Eisenhauer E. 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. J. Clin. Oncol. 2006, 24(29):4699−4707.
  33. Bolis G., Scarfone G., Giardina G., Villa A., Mangili G., Melpignano M., Presti M., Tateo S., Franchi M., Parazzini F. Associazione per la Ricerca in Ginecologia Oncologia (ARGO 96) Study Group. Carboplatin alone vs carboplatin plus epidoxorubicin as second-line therapy for cisplatin- or carboplatin-sensitive ovarian cancer,GynecolOncol. 2001 Apr, 81(1):3−9.
  34. Parmar M.K., Ledermann J.A., Colombo N., du Bois A., Delaloye J.F., Kristensen G.B., Wheeler S., Swart A.M., Qian W., Torri V., Floriani I., Jayson G., Lamont A., Trope C. Paclitaxel plus platinum based chemotherapy versus conventional platinum based chemo therapy in women with relapsed ovarian cancer: the ICON4/AGO OVAR 2.2 trial. Lancet. 2003, 361(9375):2099−2106.
  35. Alberts D.S., Liu P.Y., Wilczynski S.P., Clouser M.C., Lopez A.M., Michelin D.P., Lanzotti V.J., Markman M. Southwest Oncology Group.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). Gynecol. Oncol. 2008 Jan., 108(1):90−94.
  36. Monk B.J., Herzog T.J., Kaye S.B., Krasner C.N., Vermorken J.B., Muggia F.M., Pujade-Lauraine E., Lisyanskaya A.S., Makhson A.N., Rolski J., Gorbounova V.A., Ghatage P,. Bidzinski M., Shen K., Ngan H.Y., Vergote I.B., Nam J.H., Park Y.C., Lebedinsky C.A., Poveda A.M. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J. Clin. On-col. 2010 Jul., 28(19):3107−3114.
  37. Pujade-Lauraine E., Wagner U., Aavall-Lundqvist E., et al. Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin. Oncol. 2010. 28(20):3323–3329.
  38. Pujade-Lauraine E. How to approach patients in relapse. Ann. Oncol. 2012, 10 (23 Suppl.):128–131.
  39. Wagner U., Marth C., Largillier R., Kaern J., Brown C., Heywood M., Bonaventura T., Vergote I., Piccirillo M.C., Fossati R., Gebski V., Lauraine E.P. 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. Br. J. Cancer. 2012, 107(4):588−591.
  40. Sehouli J., Chekerov R., Reinthaller A., Richter R., Gonzalez-Martin A., Harter P., Woopen H., Petru E., Hanker LC., Keil E., Wimberger P., Klare P., Kurzeder C., Hilpert F., Belau A.K., Zeimet A., Bover-Barcelo I., Canzler U., Mahner S., Meier W. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabin plus carboplatin (GC) or carboplatin plus pegylateddoxorubicn (PLDC): A randomized phase III trial of the NOGGO AGO Germany AGO Austria and GEICO GCIG intergroup study (HECTOR). Ann. Oncol. 2016, 27(12):2236−2241.
  41. Aghajanian C., Blank S.V., Goff B.A., Judson P.L., Teneriello M.G., Husain A., Sovak M.A., Yi J., Nycum L.R. 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. J. Clin. Oncol. 2012, 10;30(17):2039−2045.
  42. Coleman R.L., Brady M.F., Herzog T.J., Sabbatini P., Armstrong D.K., Walker J.L., Kim B.G., Fujiwara K., Tewari K.S., O'Malley D.M., Davidson S.A., Rubin S.C., DiSilvestro P., Basen-Engquist K., Huang H., Chan J.K., Spirtos N.M., Ashfaq R., Mannel R.S. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytore-duction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017, 18(6):779−791.
  43. Matulonis U.A., Berlin S., Ivy P., Tyburski K., Krasner C., Zarwan C., Berkenblit A., Campos S., Horowitz N., Cannistra S.A., Lee H., Lee J., Roche M., Hill M., Whalen C., Sullivan L., Tran C., Humphreys B.D., Penson R.T. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J. Clin. Oncol. 2009, 27(33):5601−5606.
  44. Delli Carpini J., Karam A.K., Montgomery L. Vascular endothelial growth factor and relationship to the prognosis and treatment of breast, ovarian, and cervical cancer. Angiogenesis. 2010, 13(1):43−58.
  45. Ledermann J.A., Perren T.J., Raja F.A., Embleton A., Rustin G.J.S., Jayson G., Kaye S.B. Randomised double blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: results of the ICON6 trial. Cancer. 2013, 49(3):LBA10.
  46. Ferrero J.M., Weber B., Geay J.F., et al. Second-line chemotherapy with pegylated liposomal doxorubicin and carboplatin is highly effective in patients with advanced ovarian cancer in late relapse: a GINECO phase II trial. Ann Oncol. 2007, 18:263–268.
  47. Power P., Stuart G., Oza A., et al. Efficacy of pegylated liposomal doxorubicin (PLD) plus carboplatin in ovarian cancer patients who recur within six to twelve months: a phase II study. Gynecol. Oncol. 2009, 114:410–414.
  48. Rapoport B.L., Vorobiof D.A., Slabber C., et al. Phase II study of pegylated liposomal doxorubicin and carboplatin in patients with platinum-sensitive and partially platinum-sensitive metastatic ovarian cancer. Int. J. Gynecol. Cancer. 2009, 19:1137–1141.
  49. Weber B., Lortholary A,. Mayer F., et al. Pegylated liposo-mal doxorubicin andcarboplatin in late-relapsing ovarian cancer: a GINECO group phase II trial. Anticancer Res. 2009, 29:4195–4200.
  50. Mirza M.R., Lund B., Lindegaard J.C., et al. A phase II study of combination chemotherapy in early relapsed epi-thelial ovarian cancer using gemcitabine and pegylated lipo-somal doxorubicin. Gynecol. Oncol. 2010, 119:26–31.
  51. Kaye S.B., Colombo N., Monk B.J., Tjulandin S., Kong B., Roy M., Chan S., Filipczyk-Cisarz E., Hagberg H., Vergote I., Lebedinsky C., Parekh T., Santabarbara P., Park Y.C., Nieto A., Poveda A. Trabectedin plus pegylatedliposomal doxorubicin in relapsed ovarian cancer delays third line chemotherapy and prolongs the platinum free interval. Ann. Oncol. 2011, 22(1):49−58.
  52. Pfisterer J., Plante M., Vergote I., et al. Gemcitabine plus carboplatin comparedwith carboplatin in patients with plati-num-sensitive recurrent ovarian cancer: anintergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J. Clin. Oncol. 2006, 24:4699–4707.
  53. Monk B.J., Herzog T.J., Kaye S.B., et al. Trabectedin plus pegylatedliposomaldoxorubicin in recurrent ovarian cancer. J. Clin. Oncol. 2010, 28:3107–3114.
  54. Poveda A., Vergote I., Tjulandin S., et al. Trabectedin plus pegylated liposomaldoxorubicin in relapsed ovarian cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III randomized trial. Ann. Oncol. 2011, 22:39–4.
  55. Pignata S., Scambia G., Raspagliesi F., Murgia V., Pisano C., Salutari V., Bologna A., Sorio R., Ferrandina G., Sacco C., Vergote I., Cormio G., Breda E., Cinieri S., Cecere S.C., Wagner U.A.G., Daniele G., Gallo C., Perrone F., Piccirillo M.C. The MITO8 phase III international multicenter ran-domized 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. J. Clin. Oncol. 2016, 34(15):5505.