Skip to main content

Advances in the Medical Management of Ovarian Cancer

  • Chapter
  • First Online:
Pathology of the Ovary, Fallopian Tube and Peritoneum

Abstract

The term ovarian cancer includes a family of diseases with distinct anatomical, morphological, and genetic distinctions. The term is used to generally encompass tumors that are thought to arise from the ovary and the fallopian tube and also primary peritoneal carcinoma. The disease carries a poor prognosis with outlook primarily being dictated by the anatomical stage of disease at presentation. A recent analysis of the Surveillance, Epidemiology, and End Results database for US patients presenting with epithelial ovarian carcinoma between 1995 and 2007 has demonstrated a relative 10-year survival of 84 %, 59 %, 23 %, and just 8 % for FIGO stages 1, 2, 3, and 4, respectively.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Baldwin LA, Huang B, Miller RW, Tucker T, Goodrich ST, Podzielinski I, et al. Ten-year relative survival for epithelial ovarian cancer. Obstet Gynecol. 2012;120(3):612–8. doi:10.1097/AOG.0b013e318264f794.

    PubMed  Google Scholar 

  2. Mackay HJ, Brady MF, Oza AM, Reuss A, Pujade-Lauraine E, Swart AM, et al. Prognostic relevance of uncommon ovarian histology in women with stage III/IV epithelial ovarian cancer. Int J Gynecol Cancer. 2010;20(6):945–52.

    PubMed  Google Scholar 

  3. Shih I, Kurman RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 2004;164(5):1511–8. doi:S0002-9440(10)63708-X [pii].

    PubMed  CAS  PubMed Central  Google Scholar 

  4. Tothill RW, Tinker AV, George J, Brown R, Fox SB, Lade S, et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res. 2008;14(16):5198–208. doi:10.1158/1078-0432.ccr-08-0196.

    PubMed  CAS  Google Scholar 

  5. Mizuno M, Kajiyama H, Shibata K, Mizuno K, Yamamuro O, Kawai M, et al. Adjuvant chemotherapy for stage i ovarian clear cell carcinoma: is it necessary for stage IA? Int J Gynecol Cancer. 2012;22(7):1143–9. doi:10.1097/IGC.0b013e31825c7cbe.

    PubMed  Google Scholar 

  6. Takada T, Iwase H, Iitsuka C, Nomura H, Sakamoto K, Omatsu K, et al. Adjuvant chemotherapy for stage I clear cell carcinoma of the ovary: an analysis of fully staged patients. Int J Gynecol Cancer. 2012;22(4):573–8. doi:10.1097/IGC.0b013e31823fd413.

    PubMed  Google Scholar 

  7. Tan DS, Miller RE, Kaye SB. New perspectives on molecular targeted therapy in ovarian clear cell carcinoma. Br J Cancer. 2013;108(8):1553–9. doi:10.1038/bjc.2013.126.

    PubMed  CAS  PubMed Central  Google Scholar 

  8. The Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609–15.

    PubMed Central  Google Scholar 

  9. Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003;21(17):3194–200. doi:10.1200/jco.2003.02.153.

    PubMed  CAS  Google Scholar 

  10. Bodurka DC, Deavers MT, Tian CQ, Sun CC, Malpica A, Coleman RL, et al. Reclassification of serous ovarian carcinoma by a 2-tier system. Cancer. 2012;118(12):3087–94. doi:10.1002/Cncr.26618.

    PubMed  Google Scholar 

  11. Verhaak RG, Tamayo P, Yang JY, Hubbard D, Zhang H, Creighton CJ, et al. Prognostically relevant gene signatures of high-grade serous ovarian carcinoma. J Clin Invest. 2013;123(1):517–25.

    PubMed  CAS  PubMed Central  Google Scholar 

  12. Kurman RJ, Shih I. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol. 2010;34(3):433–43.

    PubMed  PubMed Central  Google Scholar 

  13. Adams M, Kerby I, Rocker I, Evans A, Johansen K, Franks C. Comparison of the toxicity and efficacy of cisplatin and carboplatin in advanced ovarian cancer. Acta Oncol. 1989;28:57–60.

    PubMed  CAS  Google Scholar 

  14. Alberts D, Green S, Hanningan E, O’Toole R, Stock-Novack D, Anderson P, et al. Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomised trial in stages III and IV ovarian cancer. J Clin Oncol. 1992;10:706–17.

    PubMed  CAS  Google Scholar 

  15. Conte P, Bruzzone M, Carnino F, Chiara S, Donadio M, Facchini V, et al. Carboplatin, doxorubicin, and cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide: a randomized trial in stage III-IV epithelial ovarian carcinoma. J Clin Oncol. 1991;9:658–63.

    PubMed  CAS  Google Scholar 

  16. Edmonson J, McCormack G, Wieand H, Kugler J, Krook J, Stanhope C, et al. Cyclophosphamide-cisplatin versus cyclophosphamide-carboplatin in stage III-IV ovarian carcinoma: a comparison of equally myelosuppressive regimens. J Natl Cancer Inst. 1989;81:1500–4.

    PubMed  CAS  Google Scholar 

  17. Hannigan E, Green S, Alberts D, O’Toole R, Surwit E. Results of a Southwest Oncology Group phase III trial of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide in advanced ovarian cancer. Oncology. 1993;50 Suppl 2:2–9.

    PubMed  Google Scholar 

  18. The ICON Collaborators. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin and cisplatin) in woman with ovarian cancer. Lancet. 1998;352:1571–6.

    Google Scholar 

  19. McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996;334(1):1–6.

    PubMed  CAS  Google Scholar 

  20. Stuart G, Mangioni C, Trope C, James K, Cassidy J, Kaye S, et al. Updated analysis shows a highly significant improved overall survival (OS) for cisplatin-paclitaxel as first line treatment of advanced ovarian cancer: mature results of the EORTC-GCCG, NOCOVA, NCIC CTG and Scottish Intergroup Trial. Proc Am Soc Clin Oncol. 1998;17:361a. Ab No. 1394.

    Google Scholar 

  21. Parmar MKB, Adams M, Balestrino M, Bertelsen K, Bonazzi C, Calvert H, et al. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002;360(9332):505–15.

    Google Scholar 

  22. Muggia FM, Braly PS, Brady MF, Sutton G, Niemann TH, Lentz SL, et al. Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a gynecologic oncology group study. J Clin Oncol. 2000;18(1):106–15.

    PubMed  CAS  Google Scholar 

  23. National Institute for Health and Care Excellence. Guidance on the use of paclitaxel in the treatment of ovarian cancer. TA55. London: National Institute for Health and Care Excellence; 2003.

    Google Scholar 

  24. National Comprehensive Cancer Network. NCCN Guidelines Version 2.2013. Epithelial ovarian cancer/Fallopian tube cancer/Primary peritoneal cancer. 2013. http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Accessed Nov 2013.

  25. Paulsen T, Kjaerheim K, Kaern J, Tretli S, Trope C. Improved short-term survival for advanced ovarian, tubal, and peritoneal cancer patients operated at teaching hospitals. Int J Gynecol Cancer. 2006;16:11–7. doi:10.1111/j.1525-1438.2006.00319.x.

    PubMed  Google Scholar 

  26. du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials By the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d’Investigateurs Nationaux Pour les Etudes des Cancers de l’Ovaire (GINECO). Cancer. 2009;115(6):1234–44. doi:10.1002/cncr.24149.

    PubMed  Google Scholar 

  27. Elattar A, Bryant A, Winter-Roach BA, Hatem M, Naik R. Optimal primary surgical treatment for advanced epithelial ovarian cancer. Cochrane Database Syst Rev. 2011(8). doi:10.1002/14651858.cd007565.

  28. Vergote I, De Wever I, Tjalma W, Van Gramberen M, Decloedt J, van Dam P. Neoadjuvant chemotherapy or primary debulking surgery in advanced ovarian carcinoma: a retrospective analysis of 285 patients. Gynecol Oncol. 1998;71(3):431–6. doi:10.1006/gyno.1998.5213.

    PubMed  CAS  Google Scholar 

  29. Vergote I, Trope CG, Amant F, Kristensen GB, Ehlen T, Johnson N, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363(10):943–53.

    PubMed  CAS  Google Scholar 

  30. Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener HC, Lopes T, et al. Chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer: results from the MRC CHORUS trial. J Clin Oncol. 2013;31(Suppl):Abstract 5500.

    Google Scholar 

  31. Onda T, Matsumoto K, Shibata T, Sato A, Fukuda H, Konishi I, et al. Phase III trial of upfront debulking surgery versus neoadjuvant chemotherapy for stage III/IV ovarian, tubal and peritoneal cancers: Japan Clinical Oncology Group Study JCOG0602. Jpn J Clin Oncol. 2008;38(1):74–7. doi:10.1093/jjco/hym145.

    PubMed  Google Scholar 

  32. Vergote I, Du BA, Amant F, Heitz F, Leunen K, Harter P. Neoadjuvant chemotherapy in advanced ovarian cancer: on what do we agree and disagree? Gynecol Oncol. 2013;128(1):6–11.

    PubMed  Google Scholar 

  33. Bookman MA, Brady MF, McGuire WP, Harper PG, Alberts DS, Friedlander M, et al. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a Phase III Trial of the Gynecologic Cancer InterGroup. J Clin Oncol. 2009;27(9):1419–25. doi:10.1200/jco.2008.19.1684.

    PubMed  CAS  PubMed Central  Google Scholar 

  34. Pfisterer J, Weber B, Reuss A, Kimmig R, du Bois A, Wagner U, et al. Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO. J Natl Cancer Inst. 2006;98(15):1036–45. doi:10.1093/jnci/djj296.

    PubMed  CAS  Google Scholar 

  35. du Bois A, Herrstedt J, Hardy-Bessard AC, Muller HH, Harter P, Kristensen G, et al. Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer. J Clin Oncol. 2010;28(27):4162–9. doi:10.1200/JCO.2009.27.4696. doi:JCO.2009.27.4696 [pii].

    PubMed  Google Scholar 

  36. Ledermann JA. Lessons learned from a decade of clinical trials of high-dose chemotherapy in ovarian cancer. Int J Gynecol Cancer. 2008;18 Suppl 1:53–8. doi:10.1111/j.1525-1438.2007.01107.x.

    PubMed  Google Scholar 

  37. Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354(1):34–43.

    PubMed  CAS  Google Scholar 

  38. Cancer Therapy Evaluation Program. NCI clinical announcement on intraperitoneal chemotherapy in ovarian cancer (5 Jan 2006). 2006. http://ctep.cancer.gov/highlights/20060105_ovarian.htm. Accessed Nov 2013.

  39. UK Clinical Research Network Study Portfolio. PETROC/OV21: a phase II/III study of intraperitoneal (IP) plus intravenous (IV) chemotherapy versus IV carboplatin plus paclitaxel in patients with epithelial ovarian cancer optimally Debulked at surgery following neoadjuvant intravenous chemotherapy: A Gynecologic Cancer Intergroup (GCIG) Trial led by the NCIC CTG 2013. http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=7472. Accessed Nov 2013.

  40. Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, et al. 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. 2009;374(9698):1331–8.

    PubMed  CAS  Google Scholar 

  41. Katsumata N, Yasuda M, Isonishi S, Takahashi F, Michimae H, Kimura E, et al. 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. Lancet Oncol. 2013;14(10):1020–6. doi:10.1016/S1470-2045(13)70363-2.

    PubMed  CAS  Google Scholar 

  42. Pignata S, Scambia G, Lauria R, Raspagliesi F, Benedetti Panici P, Cormio G, et al. A randomized multicenter phase III study comparing weekly versus every 3 weeks carboplatin (C) plus paclitaxel (P) in patients with advanced ovarian cancer (AOC): Multicenter Italian Trials in Ovarian Cancer (MITO-7) – European Network of Gynaecological Oncological Trial Groups (ENGOT-ov-10) and Gynecologic Cancer Intergroup (GCIG) trial. ASCO Meeting Abstracts. 2013;31(18_suppl):LBA5501.

    Google Scholar 

  43. ClinicalTrials.gov. Paclitaxel and carboplatin with or without bevacizumab in treating patients with stage II, stage III, or stage IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer [NCT01167712]. 2013. http://clinicaltrials.gov/show/NCT01167712. Accessed 31 Jan 2014.

  44. ClinicalTrials.gov. ICON8: weekly chemotherapy in ovarian cancer [NCT01654146]. 2012. http://clinicaltrials.gov/ct2/show/NCT01654146. Accessed 31 Jan 2014.

  45. Markman M, Liu PY, Wilczynski S, Monk B, Copeland LJ, Alvarez RD, et al. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group Trial. J Clin Oncol. 2003;21(13):2460–5. doi:10.1200/jco.2003.07.013.

    PubMed  CAS  Google Scholar 

  46. Hall GD, Brown JM, Coleman RE, Stead M, Metcalf KS, Peel KR, et al. Maintenance treatment with interferon for advanced ovarian cancer: results of the Northern and Yorkshire gynaecology group randomised phase III study. Br J Cancer. 2004;91(4):621–6. doi:10.1038/sj.bjc.6602037.

    PubMed  CAS  PubMed Central  Google Scholar 

  47. Banerjee S, Kaye SB. New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential. Clin Cancer Res. 2013;19(5):961–8. doi:10.1158/1078-0432.Ccr-12-2243.

    PubMed  CAS  Google Scholar 

  48. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434:913–7.

    PubMed  CAS  Google Scholar 

  49. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–21.

    PubMed  CAS  Google Scholar 

  50. Fong PC, Boss DS, Yap TA, Tutt A, Wu PJ, Mergui-Roelvink M, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361(2):123–34. doi:10.1056/Nejmoa0900212.

    PubMed  CAS  Google Scholar 

  51. Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, 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. Lancet. 2010;376(9737):245–51. doi:10.1016/S0140-6736(10)60893-8.

    PubMed  CAS  Google Scholar 

  52. Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, et al. 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. Lancet Oncol. 2011;12(9):852–61. doi:10.1016/S1470-2045(11)70214-5.

    PubMed  CAS  Google Scholar 

  53. Ledermann JA, Hackshaw A, Kaye S, Jayson G, Gabra H, McNeish I, et al. Randomized phase II placebo-controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer. J Clin Oncol. 2011;29(28):3798–804. doi:10.1200/Jco.2010.33.5208.

    PubMed  CAS  Google Scholar 

  54. Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin GJS, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer (SOC) and a BRCA mutation (BRCAm). ASCO Meeting Abstracts. 2013;31(15_suppl):5505.

    Google Scholar 

  55. Oza AM, Cibula D, Oaknin A, Poole CJ, Mathijssen RHJ, Sonke GS, et al. Olaparib plus paclitaxel plus carboplatin (P/C) followed by olaparib maintenance treatment in patients (pts) with platinum-sensitive recurrent serous ovarian cancer (PSR SOC): a randomized, open-label phase II study. J Clin Oncol. 2012;30(15).

    Google Scholar 

  56. Oza AM, Cibula D, Benzaquen AO, Poole CJ, Mathijssen RHJ, Sonke GS, et al. Olaparib plus chemotherapy, followed by maintenance monotherapy, in women with platinum-sensitive recurrent serous ovarian cancer (PSR SOC): BRCA1/2 mutation (BRCAm) and interim overall survival analyses. Eur J Cancer. 2013;49:S712–3.

    Google Scholar 

  57. ClinicalTrials.gov. Olaparib monotherapy in patients with BRCA mutated ovarian cancer following first line platinum based chemotherapy [NCT01844986]. 2014. http://clinicaltrials.gov/ct2/show/record/NCT01844986. Accessed 31 Jan 2014.

  58. ClinicalTrials.gov. Olaparib treatment in BRCA mutated ovarian cancer patients after complete or partial response to platinum chemotherapy [NCT01874353]. 2014. http://www.clinicaltrials.gov/ct2/show/NCT01874353. Accessed 31 Jan 2014.

  59. ClinicalTrials.gov. A study of rucaparib in patients with platinum-sensitive, relapsed, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer (ARIEL2) [NCT01891344]. 2014. http://clinicaltrials.gov/show/NCT01891344. Accessed 31 Jan 2014.

  60. ClinicalTrials.gov. A study of rucaparib as switch maintenance following platinum-based chemotherapy in patients with platinum-sensitive, high-grade serous or endometrioid epithelial ovarian, primary peritoneal or fallopian tube cancer (ARIEL3) [NCT01968213]. 2014. http://clinicaltrials.gov/ct2/show/NCT01968213. Accessed 31 Jan 2014.

  61. Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365(26):2484–96. doi:10.1056/Nejmoa1103799.

    PubMed  CAS  Google Scholar 

  62. Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473–83. doi:10.1056/NEJMoa1104390.

    PubMed  CAS  Google Scholar 

  63. Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, et al. 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;30(17):2039–45.

    PubMed  CAS  PubMed Central  Google Scholar 

  64. Pujade-Lauraine E, Hilpert F, Weber B, Reuss A. AURELIA: a randomized phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant recurrent ovarian cancer (OC). J Clin Oncol. 2012;30, 2012(suppl; abstr LBA5002)(0).

    Google Scholar 

  65. Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438(7070):932–6.

    PubMed  CAS  Google Scholar 

  66. Carmeliet P, Jain RK. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov. 2011;10(6):417–27. doi:10.1038/nrd3455.

    PubMed  CAS  Google Scholar 

  67. Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 2002;29(6 Suppl 16):15–8. doi:10.1053/sonc.2002.37263.

    PubMed  CAS  Google Scholar 

  68. Jain RK, Carmeliet P. SnapShot: Tumor angiogenesis. Cell. 2012;149(6):1408–e1. doi:10.1016/j.cell.2012.05.025.

    PubMed  CAS  Google Scholar 

  69. Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med. 2001;7(9):987–9. doi:10.1038/nm0901-987.

    PubMed  CAS  Google Scholar 

  70. Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature. 1993;362(6423):841–4. doi:10.1038/362841a0.

    PubMed  CAS  Google Scholar 

  71. Hartenbach EM, Olson TA, Goswitz JJ, Mohanraj D, Twiggs LB, Carson LF, et al. Vascular endothelial growth factor (VEGF) expression and survival in human epithelial ovarian carcinomas. Cancer Lett. 1997;121(2):169–75.

    PubMed  CAS  Google Scholar 

  72. Nakanishi Y, Kodama J, Yoshinouchi M, Tokumo K, Kamimura S, Okuda H, et al. The expression of vascular endothelial growth factor and transforming growth factor-beta associates with angiogenesis in epithelial ovarian cancer. Int J Gynecol Pathol. 1997;16(3):256–62.

    PubMed  CAS  Google Scholar 

  73. Yamamoto S, Konishi I, Mandai M, Kuroda H, Komatsu T, Nanbu K, 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(9):1221–7.

    PubMed  CAS  PubMed Central  Google Scholar 

  74. Ramakrishnan S, Subramanian IV, Yokoyama Y, Geller M. Angiogenesis in normal and neoplastic ovaries. Angiogenesis. 2005;8(2):169–82. doi:10.1007/s10456-005-9001-1.

    PubMed  CAS  Google Scholar 

  75. Byrne AT, Ross L, Holash J, Nakanishi M, Hu L, Hofmann JI, 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(15):5721–8.

    PubMed  CAS  Google Scholar 

  76. Mabuchi S, Terai Y, Morishige K, Tanabe-Kimura A, Sasaki H, Kanemura M, et al. Maintenance treatment with bevacizumab prolongs survival in an in vivo ovarian cancer model. Clin Cancer Res. 2008;14(23):7781–9. doi:10.1158/1078-0432.CCR-08-0243.

    PubMed  CAS  Google Scholar 

  77. Santin AD, Hermonat PL, Ravaggi A, Cannon MJ, Pecorelli S, Parham GP. Secretion of vascular endothelial growth factor in ovarian cancer. Eur J Gynaecol Oncol. 1999;20(3):177–81.

    PubMed  CAS  Google Scholar 

  78. Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Merino MJ. Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol. 1995;147(1):33–41.

    PubMed  CAS  PubMed Central  Google Scholar 

  79. Shen GH, Ghazizadeh M, Kawanami O, Shimizu H, Jin E, Araki T, et al. Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma. Br J Cancer. 2000;83(2):196–203. doi:10.1054/bjoc.2000.1228.

    PubMed  CAS  PubMed Central  Google Scholar 

  80. Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. 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(33):5165–71. doi:10.1200/JCO.2007.11.5345.

    PubMed  CAS  Google Scholar 

  81. Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007;25(33):5180–6. doi:10.1200/JCO.2007.12.0782.

    PubMed  CAS  Google Scholar 

  82. Micha JP, Goldstein BH, Rettenmaier MA, Genesen M, Graham C, Bader K, et al. A phase II study of outpatient first-line paclitaxel, carboplatin, and bevacizumab for advanced-stage epithelial ovarian, peritoneal, and fallopian tube cancer. Int J Gynecol Cancer. 2007;17(4):771–6. doi:10.1111/j.1525-1438.2007.00886.x.

    PubMed  CAS  Google Scholar 

  83. Penson RT, Dizon DS, Cannistra SA, Roche MR, Krasner CN, Berlin ST, et al. Phase II study of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab as first-line chemotherapy for advanced mullerian tumors. J Clin Oncol. 2010;28(1):154–9. doi:10.1200/JCO.2009.22.7900.

    PubMed  CAS  Google Scholar 

  84. Kaye SB. Bevacizumab for the treatment of epithelial ovarian cancer: will this be its finest hour? J Clin Oncol. 2007;25(33):5150–2. doi:10.1200/JCO.2007.13.6150.

    PubMed  CAS  Google Scholar 

  85. O’Malley DM, Richardson DL, Rheaume PS, Salani R, Eisenhauer EL, McCann GA, et al. Addition of bevacizumab to weekly paclitaxel significantly improves progression-free survival in heavily pretreated recurrent epithelial ovarian cancer. Gynecol Oncol. 2011;121(2):269–72. doi:10.1016/j.ygyno.2011.01.009.

    PubMed  Google Scholar 

  86. Tillmanns TD, Lowe MP, Walker MS, Stepanski EJ, Schwartzberg LS. Phase II clinical trial of bevacizumab with albumin-bound paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma. Gynecol Oncol. 2012. doi:10.1016/j.ygyno.2012.08.039.

    Google Scholar 

  87. Kudoh K, Takano M, Kouta H, Kikuchi R, Kita T, Miyamoto M, et al. Effects of bevacizumab and pegylated liposomal doxorubicin for the patients with recurrent or refractory ovarian cancers. Gynecol Oncol. 2011;122(2):233–7.

    PubMed  CAS  Google Scholar 

  88. McGonigle KF, Muntz HG, Vuky J, Paley PJ, Veljovich DS, Greer BE, et al. Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer: results of a phase 2 study. Cancer. 2011;117(16):3731–40. doi:10.1002/cncr.25967.

    PubMed  CAS  Google Scholar 

  89. Kristensen G, Perren T, Qian W, Pfisterer J, Ledermann J, Joly F, et al. editors. Result of interim analysis of overall survival in the GCIG ICON7 phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer. American Society of Clinical Oncology, J Clin Oncol. 2011; Chicago.

    Google Scholar 

  90. Royston P, Parmar MK. The use of restricted mean survival time to estimate the treatment effect in randomized clinical trials when the proportional hazards assumption is in doubt. Stat Med. 2011;30(19):2409–21. doi:10.1002/sim.4274.

    PubMed  Google Scholar 

  91. Oza AM, Perren TJ, Swart AM, Schroder W, Pujade-Lauraine E, Havsteen H, et al. ICON7: Final overall survival results in the GCIG phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer. Eur J Cancer. 2013;49:S4–S.

    Google Scholar 

  92. Witteveen P, Lortholary A, Fehm T, Poveda A, Reuss A, Havsteen H, et al. LATE BREAKING ABSTRACT: Final overall survival (OS) results from AURELIA, an open-label randomised phase III trial of chemotherapy (CT) with or without bevacizumab (BEV) for platinum-resistant recurrent ovarian cancer (OC). Eur J Cancer. 2013;49:S3–4.

    Google Scholar 

  93. Monk BJ, Huang HQ, Burger RA, Mannel RS, Homesley HD, Fowler J, et al. Patient reported outcomes of a randomized, placebo-controlled trial of bevacizumab in the front-line treatment of ovarian cancer: a Gynecologic Oncology Group Study. Gynecol Oncol. 2013;128(3):573–8. doi:10.1016/j.ygyno.2012.11.038.

    PubMed  CAS  PubMed Central  Google Scholar 

  94. Stark D, Nankivell M, Pujade-Lauraine E, Kristensen G, Elit L, Stockler M, et al. Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol. 2013;14(3):236–43. doi:10.1016/S1470-2045(12)70567-3.

    PubMed  PubMed Central  Google Scholar 

  95. Cohn DE, Kim KH, Resnick KE, O’Malley DM, Straughn Jr JM. At what cost does a potential survival advantage of bevacizumab make sense for the primary treatment of ovarian cancer? A cost-effectiveness analysis. J Clin Oncol. 2011;29(10):1247–51. doi:10.1200/JCO.2010.32.1075.

    PubMed  Google Scholar 

  96. Lesnock JL, Farris C, Krivak TC, Smith KJ, Markman M. Consolidation paclitaxel is more cost-effective than bevacizumab following upfront treatment of advanced epithelial ovarian cancer. Gynecol Oncol. 2011;122(3):473–8. doi:10.1016/j.ygyno.2011.05.014.

    PubMed  CAS  PubMed Central  Google Scholar 

  97. Lechuga D, Alva M, Carlos F. PCN75 economic evaluation of bevacizumab for the treatment of advanced ovarian cancer in Mexico. Value Health. 2012;15(4):A221. doi:http://dx.doi.org/10.1016/j.jval.2012.03.1192.

  98. National Institute for Health and Care Excellence. Bevacizumab in combination with paclitaxel and carboplatin for first-line treatment of advanced ovarian cancer [TA284]. London: National Institute for Health and Care Excellence; 2013.

    Google Scholar 

  99. National Institute for Health and Care Excellence. Bevacizumab in combination with gemcitabine and carboplatin for treating the first recurrence of platinum-sensitive advanced ovarian cancer [TA285]. London: National Institute for Health and Care Excellence; 2013.

    Google Scholar 

  100. NHS England. National Cancer Drugs Fund List (updated 30 Sept 2013). 2013. http://www.england.nhs.uk/wp-content/uploads/2013/09/ncdf-list-sept.pdf. Accessed 17 Jan 2014.

  101. NHS England. Bevacizumab in combination with carboplatin and gemcitabine for treatment of adult patients with first recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor–targeted agents. 2013. http://www.england.nhs.uk/wp-content/uploads/2013/10/bevac-plat-apr.pdf. Accessed 17 Jan 2014.

  102. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Ovarian cancer including fallopian tube cancer and primary peritoneal cancer. 2013. http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Accessed 17 Jan 2014.

  103. Klement G, Baruchel S, Rak J, Man S, Clark K, Hicklin DJ, et al. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest. 2000;105(8):R15–24. doi:10.1172/JCI8829.

    PubMed  CAS  PubMed Central  Google Scholar 

  104. Frumovitz M, Sood AK. Vascular endothelial growth factor (VEGF) pathway as a therapeutic target in gynecologic malignancies. Gynecol Oncol. 2007;104(3):768–78. doi:10.1016/j.ygyno.2006.10.062.

    PubMed  CAS  PubMed Central  Google Scholar 

  105. ClinicalTrials.gov. A study of the addition of Avastin (bevacizumab) to carboplatin and paclitaxel therapy in patients with ovarian cancer [NCT01239732]. 2014. http://clinicaltrials.gov/show/NCT01239732. Accessed 17 Jan 2014.

  106. ClinicalTrials.gov. Evaluation of optimal initial treatment duration of bevacizumab in combination with standard chemotherapy in patients with ovarian cancer (BOOST) [NCT01462890]. 2012. http://clinicaltrials.gov/ct2/show/NCT01462890?term=NCT01462890. Accessed 17 Jan 2014.

  107. Bennouna J, Sastre J, Arnold D, Osterlund P, Greil R, Van Cutsem E, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013;14(1):29–37. doi:10.1016/s1470-2045(12)70477-1.

    PubMed  CAS  Google Scholar 

  108. Jayson GC, Hicklin DJ, Ellis LM. Antiangiogenic therapy–evolving view based on clinical trial results. Nat Rev Clin Oncol. 2012;9(5):297–303. doi:10.1038/nrclinonc.2012.8.

    PubMed  CAS  Google Scholar 

  109. ClinicalTrials.gov. Bevacizumab beyond progression in platinum sensitive ovarian cancer (MITO16MANGO2b) [NCT01802749]. 2013. http://clinicaltrials.gov/ct2/show/NCT01802749?term=NCT01802749. Accessed 17 Jan 2014.

  110. ClinicalTrials.gov. Carboplatin, paclitaxel and gemcitabine with or without bevacizumab after surgery in treating patients with recurrent ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer [NCT00565851]. 2013. http://clinicaltrials.gov/ct2/show/NCT00565851?term=NCT00565851. Accessed 17 Jan 2014.

  111. ClinicalTrials.gov. A study of first line treatment with Avastin (bevacizumab) in combination with carboplatin and weekly paclitaxel in patients with ovarian cancer (Octavia) [NCT00937560]. 2014. http://clinicaltrials.gov/ct2/show/NCT00937560?term=NCT00937560. Accessed 17 Jan 2014.

  112. ClinicalTrials.gov. Paclitaxel and carboplatin with or without bevacizumab in treating patients with stage II, stage III, or stage IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer (GOG-262) [NCT01167712]. 2013. http://clinicaltrials.gov/ct2/show/NCT01167712?term=NCT01167712. Accessed 17 Jan 2014.

  113. ClinicalTrials.gov. Bevacizumab and intravenous or intraperitoneal chemotherapy in treating patients with stage II, stage III, or stage IV ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer (GOG-252) [NCT00951496]. 2013. http://clinicaltrials.gov/ct2/show/NCT00951496?term=NCT00951496. Accessed 17 Jan 2014.

  114. Du Bois A, Floquet A, Kim JW, Rau J, Del Campo JM, Friedlander M, et al. 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). ASCO Meeting Abstracts. 2013;31(18_suppl):LBA5503.

    Google Scholar 

  115. Friedlander M, Hancock KC, Rischin D, Messing MJ, Stringer CA, Matthys GM, et al. A phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. Gynecol Oncol. 2010;119(1):32–7. doi:10.1016/j.ygyno.2010.05.033.

    PubMed  CAS  Google Scholar 

  116. Friedlander M, Knoll S, Meier W, Lesoin A, Kim JW, Poveda A, et al. Quality of life in patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC) receiving either pazopanib monotherapy or placebo after first-line chemotherapy: AGO-OVAR16 results [Abstract 3003]. Eur J Cancer. 2013;49:S713–S.

    Google Scholar 

  117. Matulonis UA, Berlin S, Ivy P, Tyburski K, Krasner C, Zarwan C, et al. 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):5601–6. doi:10.1200/Jco.2009.23.2777.

    PubMed  CAS  PubMed Central  Google Scholar 

  118. Ledermann J, Perren T, Raja F, Embleton A, Rustin G, Jayson G, et al. Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: results of the ICON6 trial [Abstract LBA10]. Eur J Cancer. 2013;49 Suppl 3:S5–6.

    Google Scholar 

  119. Monk B, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, et al. 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[Abstract LB41]. Eur J Cancer. 2013;49 Suppl 3:S18.

    Google Scholar 

  120. ClinicalTrials.gov. TRINOVA-2: trebananib in ovarian cancer-2 [NCT01281254]. 2013. http://clinicaltrials.gov/show/NCT01281254. Accessed 25 Jan 2014.

  121. ClinicalTrials.gov. TRINOVA-3: a study of AMG 386 or AMG 386 Placebo in combination with paclitaxel and carboplatin to treat ovarian cancer [NCT01493505]. 2014. http://clinicaltrials.gov/ct2/show/NCT01493505. Accessed 25 Jan 2014.

  122. du Bois A, Kristensen G, Ray-Coquard I, Reuß A, Pignata S, Colombo N et al. Ago-ovar 12: a randomized placebo-controlled GCIG/ENGOT intergroup phase III trial of standard frontline chemotherapy +/- nintedanib for advanced ovarian cancer. Int J Gynecol Cancer. 2013;23(8 (Suppl 1)).

    Google Scholar 

  123. ClinicalTrials.gov. Daily low dose chemotherapy and BIBF 1120 in advanced ovarian cancer (METRO-BIBF) [NCT01610869]. 2012. http://clinicaltrials.gov/ct2/show/NCT01610869. Accessed 31 Jan 2014.

  124. ClinicalTrials.gov. Vargatef in addition to first line chemotherapy with interval Debulking surgery in patients with ovarian cancer (CHIVA) [NCT01583322]. 2014. http://clinicaltrials.gov/ct2/show/NCT01583322. Accessed 31 Jan 2014.

  125. Romero I, Sun CC, Wong KK, Bast RC, Gershenson DM. Low-grade serous carcinoma: new concepts and emerging therapies. Gynecol Oncol. 2013;130(3):660–6. doi:10.1016/j.ygyno.2013.05.021.

    PubMed  Google Scholar 

  126. Malpica A, Deavers MT, Lu K, Bodurka DC, Atkinson EN, Gershenson DM, et al. Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol. 2004;28:496–504.

    PubMed  Google Scholar 

  127. Wong K-K, Lu KH, Malpica A, Bodurka DC, Shvartsman HS, Schmandt RE, et al. Significantly greater expression of ER, PR, and ECAD in advanced-stage low-grade ovarian serous carcinoma as revealed by immunohistochemical analysis. Int J Gynecol Pathol. 2007;26(4):404–9. doi:10.1097/pgp.0b013e31803025cd.

    PubMed  Google Scholar 

  128. Ahlgren J, Ellison N, Gottlieb R, Laluna F, Lokich J, Sinclair P, et al. Hormonal palliation of chemoresistant ovarian cancer: three consecutive phase II trials of the Mid Atlantic Oncology program. J Clin Oncol. 1993;11(10):1957–68.

    PubMed  CAS  Google Scholar 

  129. Smyth JF, Gourley C, Walker G, MacKean MJ, Stevenson A, Williams ARW, et al. Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen receptor-positive patients. Clin Cancer Res. 2007;13(12):3617–22.

    PubMed  CAS  Google Scholar 

  130. Argenta PA, Thomas SG, Judson PL, Downs Jr LS, Geller MA, Carson LF, et al. A phase II study of fulvestrant in the treatment of multiply-recurrent epithelial ovarian cancer. Gynecol Oncol. 2009;113(2):205–9. doi:http://dx.doi.org/10.1016/j.ygyno.2009.01.012.

  131. Williams C, Simera I, Bryant A. Tamoxifen for relapse of ovarian cancer. Cochrane Database Syst Rev. 2010(3):CD001034. doi:10.1002/14651858.CD001034.pub2.

  132. Argenta PA, Um I, Kay C, Harrison D, Faratian D, Sueblinvong T, et al. Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer. Gynecol Oncol. 2013;131(2):368–73. doi:10.1016/j.ygyno.2013.07.099.

    PubMed  CAS  Google Scholar 

  133. Bowman A, Gabra H, Langdon SP, Lessells A, Stewart M, Young A, et al. CA125 response is associated with estrogen receptor expression in a phase II trial of letrozole in ovarian cancer: identification of an endocrine-sensitive subgroup. Clin Cancer Res. 2002;8(7):2233–9.

    PubMed  CAS  Google Scholar 

  134. Gershenson DM, Sun CC, Iyer RB, Malpica AL, Kavanagh JJ, Bodurka DC, et al. Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum. Gynecol Oncol. 2012;125(3):661–6. doi:10.1016/j.ygyno.2012.02.037.

    PubMed  CAS  Google Scholar 

  135. Schlumbrecht MP, Sun CC, Wong KN, Broaddus RR, Gershenson DM, Bodurka DC. Clinicodemographic factors influencing outcomes in patients with low-grade serous ovarian carcinoma. Cancer. 2011;117(16):3741–9. doi:10.1002/cncr.25929.

    PubMed  Google Scholar 

  136. Farley J, Brady WE, Vathipadiekal V, Lankes HA, Coleman R, Morgan MA, et al. Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study. Lancet Oncol. 2013;14(2):134–40. doi:10.1016/S1470-2045(12)70572-7.

    PubMed  CAS  PubMed Central  Google Scholar 

  137. ClinicalTrials.gov. Trial of Pimasertib with SAR245409 or Placebo in ovarian cancer [NCT01936363]. 2013. http://clinicaltrials.gov/show/NCT01936363. Accessed 22 Jan 2014.

  138. Takakura S, Takano M, Takahashi F, Saito T, Aoki D, Inaba N, et al. Randomized phase II trial of paclitaxel plus carboplatin therapy versus irinotecan plus cisplatin therapy as first-line chemotherapy for clear cell adenocarcinoma of the ovary a JGOG study. Int J Gynecol Cancer. 2010;20(2):240–7. doi:10.1111/IGC.0b013e3181cafb47.

    PubMed  Google Scholar 

  139. Kitasato Institute Clinical Trial Coordinating Center. Randomised phase III trial of paclitaxel plus carboplatin (TC) therapy versus irinotecan plus cisplatin (CPT-P) therapy as a first line chemotherapy for clear cell carcinoma of the ovary. EU Clinical Trials Register. https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-007849-13. Accessed 14 Jan 2014.

  140. Anglesio MS, Carey MS, Koebel M, MacKay H, Huntsman DG. Vancouver ovarian clear cell S. Clear cell carcinoma of the ovary: a report from the first ovarian clear cell symposium, June 24th, 2010. Gynecol Oncol. 2011;121(2):407–15.

    PubMed  Google Scholar 

  141. del Carmen MG, Birrer M, Schorge JO. Clear cell carcinoma of the ovary: a review of the literature. Gynecol Oncol. 2012;126(3):481–90. doi:10.1016/j.ygyno.2012.04.021.

    PubMed  Google Scholar 

  142. Penson RT, Dizon DS, Birrer MJ. Clear cell cancer of the ovary. Curr Opin Oncol. 2013;25(5):553–7. doi:10.1097/CCO.0b013e328363e0c7.

    PubMed  CAS  Google Scholar 

  143. ClinicalTrials.gov. Sunitinib® in patients with recurrent ovarian clear cell carcinoma. http://clinicaltrials.gov/ct2/show/NCT01824615?term=NCT01824615&rank=1. Accessed 14 Jan 2014.

  144. ClinicalTrials.gov. Temsirolimus, carboplatin, and paclitaxel as first-line therapy in treating patients with newly diagnosed stage III-IV clear cell ovarian cancer. http://clinicaltrials.gov/ct2/show/study/NCT01196429?term=NCT01196429&rank=1. Accessed 14 Jan 2014.

  145. Naik JD, Seligmann J, Perren TJ. Mucinous tumours of the ovary. J Clin Pathol. 2012;65(7):580–4. doi:10.1136/jclinpath-2011-200320.

    PubMed  CAS  Google Scholar 

  146. Tognon G, Carnazza M, Ragnoli M, Calza S, Ferrari F, Gambino A, et al. Prognostic factors in early-stage ovarian cancer. Ecancermedicalscience. 2013;7:325. doi:10.3332/ecancer.2013.325.

    PubMed  PubMed Central  Google Scholar 

  147. Hess V, A’Hern R, Nasiri N, King DM, Blake PR, Barton DPJ, et al. Mucinous epithelial ovarian cancer: a separate entity requiring specific treatment. J Clin Oncol. 2004;22(6):1040–4. doi:10.1200/Jco.2004.08.078.

    PubMed  CAS  Google Scholar 

  148. Stuart GC, Kitchener H, Bacon M, duBois A, Friedlander M, Ledermann J, et al. 2010 Gynecologic Cancer InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer: report from the Fourth Ovarian Cancer Consensus Conference. Int J Gynecol Cancer. 2011;21(4):750–5.

    PubMed  Google Scholar 

  149. Sundar S, Symonds RP, Decatris MP, Kumar DM, Osman A, Vasanthan S, et al. Phase II trial of Oxaliplatin and 5-Fluorouracil/Leucovorin combination in epithelial ovarian carcinoma relapsing within 2 years of platinum-based therapy. Gynecol Oncol. 2004;94(2):502–8. doi:10.1016/j.ygyno.2004.04.020.

    PubMed  CAS  Google Scholar 

  150. Pectasides D, Pectasides M, Farmakis D, Gaglia A, Koumarianou A, Nikolaou M, et al. Oxaliplatin plus high-dose leucovorin and 5-fluorouracil (FOLFOX 4) in platinum-resistant and taxane-pretreated ovarian cancer: a phase II study. Gynecol Oncol. 2004;95(1):165–72. doi:10.1016/j.ygyno.2004.06.029.

    PubMed  CAS  Google Scholar 

  151. Sato S, Itamochi H, Kigawa J, Oishi T, Shimada M, Sato S, et al. Combination chemotherapy of oxaliplatin and 5-fluorouracil may be an effective regimen for mucinous adenocarcinoma of the ovary: a potential treatment strategy. Cancer Sci. 2009;100(3):546–51. doi:10.1111/j.1349-7006.2008.01065.x.

  152. Shimizu Y, Nagata H, Kikuchi Y, Umezawa S, Hasumi K, Yokokura T. Cytotoxic agents active against mucinous adenocarcinoma of the ovary. Oncol Rep. 1998;5(1):99–101.

    PubMed  CAS  Google Scholar 

  153. McAlpine JN, Wiegand KC, Vang R, Ronnett BM, Adamiak A, Kobel M, et al. HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy. BMC Cancer. 2009;9:433. doi:10.1186/1471-2407-9-433.

    PubMed  PubMed Central  Google Scholar 

  154. Sato N, Saga Y, Mizukami H, Wang D, Fujiwara H, Takei Y, et al. Cetuximab inhibits the growth of mucinous ovarian carcinoma tumor cells lacking KRAS gene mutations. Oncol Rep. 2012;27(5):1336–40. doi:10.3892/or.2012.1626.

    PubMed  CAS  Google Scholar 

  155. Wang Y, Kaiser CE, Frett B, Li H-y. Targeting mutant KRAS for anticancer therapeutics: a review of novel small molecule modulators. J Med Chem. 2013;56(13):5219–30. doi:10.1021/jm3017706.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Timothy John Perren MBBS, MD, FRCP .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag London

About this chapter

Cite this chapter

Perren, T.J., Al-Terkait, F., Sim, S. (2014). Advances in the Medical Management of Ovarian Cancer. In: Wilkinson, N. (eds) Pathology of the Ovary, Fallopian Tube and Peritoneum. Essentials of Diagnostic Gynecological Pathology. Springer, London. https://doi.org/10.1007/978-1-4471-2942-4_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-2942-4_4

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-2941-7

  • Online ISBN: 978-1-4471-2942-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics