Annals of Surgical Oncology

, Volume 19, Issue 7, pp 2352–2359 | Cite as

Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion in Women with Heavily Pretreated Recurrent Ovarian Cancer

  • Wim P. Ceelen
  • Yves Van Nieuwenhove
  • Simon Van Belle
  • Hannelore Denys
  • Piet Pattyn
Gynecologic Oncology



Limited data are available on the use of cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (HIPEC) in patients with recurrent stage III ovarian cancer.


Patients with recurrent, heavily pretreated ovarian cancer were enrolled onto a phase II multimodal protocol consisting of extensive cytoreduction followed by HIPEC.


Forty-two women were treated from October 2002 until January 2009. Chemoperfusion was performed with cisplatin in 59% and oxaliplatin in 41% of patients. A macroscopically complete resection was achieved in 50% of patients. No mortality occurred, and the major morbidity rate was 21%. After a mean follow-up of 21 months, median overall survival (OS) was 37 months (95% confidence interval 12.2–61.8) and median progression-free survival was 13 months (95% confidence interval 6.9–19.1). In univariate analysis, OS was influenced by completeness of cytoreduction, type of chemoperfusion drug, nodal status, and tumor grade. In a Cox regression model, only completeness of cytoreduction (hazard ratio 0.06–0.8, P = .022) and tumor grade (hazard ratio 1.23–12.6, P = .021) were independent predictors of OS.


In selected patients with heavily pretreated recurrent ovarian cancer, cytoreduction combined with HIPEC may provide a meaningful OS with acceptable morbidity. Optimal results are achieved in patients with a macroscopically complete resection and biologically favorable disease.


  1. 1.
    Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.PubMedCrossRefGoogle Scholar
  2. 2.
    Ferlay J, Autier P, Boniol M, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007;18:581–92.PubMedCrossRefGoogle Scholar
  3. 3.
    Heintz APM, Odicino F, Maisonneuve P, et al. Carcinoma of the ovary. Int J Gynecol Obstet. 2006;95:S161–92.CrossRefGoogle Scholar
  4. 4.
    Leitao MM, Chi DS. Surgical management of recurrent ovarian cancer. Semin Oncol. 2009;36:106–11.PubMedCrossRefGoogle Scholar
  5. 5.
    Bristow RE, Puri I, Chi DS. Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol. 2009;112:265–74.PubMedCrossRefGoogle Scholar
  6. 6.
    Harter P, Hahmann M, Lueck HJ, et al. Surgery for recurrent ovarian cancer: role of peritoneal carcinomatosis: exploratory analysis of the DESKTOP I Trial about risk factors, surgical implications, and prognostic value of peritoneal carcinomatosis. Ann Surg Oncol. 2009;16:1324–30.PubMedCrossRefGoogle Scholar
  7. 7.
    Alberts DS, Liu PY, Hannigan EV, et al. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996;335:1950–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Markman M, Bundy BN, Alberts DS, et al. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001;19:1001–7.PubMedGoogle Scholar
  9. 9.
    Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34–43.PubMedCrossRefGoogle Scholar
  10. 10.
    Spratt JS, Adcock RA, Muskovin M, Sherrill W, Mckeown J. Clinical delivery system for intra-peritoneal hyperthermic chemotherapy. Cancer Res. 1980;40:256–60.PubMedGoogle Scholar
  11. 11.
    Issels RD. Hyperthermia adds to chemotherapy. Eur J Cancer. 2008;44:2546–54.PubMedCrossRefGoogle Scholar
  12. 12.
    Cotte E, Glehen O, Mohamed F, et al. Cytoreductive surgery and intraperitoneal chemohyperthermia for chemoresistant and recurrent advanced epithelial ovarian cancer: prospective study of 81 patients. World J Surg. 2007;31:1813–21.PubMedCrossRefGoogle Scholar
  13. 13.
    Ryu KS, Kim JH, Ko HS, et al. Effects of intraperitoneal hyperthermic chemotherapy in ovarian cancer. Gynecol Oncol. 2004;94:325–32.PubMedCrossRefGoogle Scholar
  14. 14.
    Bijelic L, Jonson A, Sugarbaker PH. Systematic review of cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis in primary and recurrent ovarian cancer. Ann Oncol. 2007;18:1943–50.PubMedCrossRefGoogle Scholar
  15. 15.
    Swellengrebel HAM, Verwaal VJ, Smeenk RM, Antonini N, Zoetmulder FAN. Quantitative intra-operative assessment of peritoneal carcinomatosis—a comparison of three prognostic tools. Eur J Cancer. Suppl 2007;5:258.CrossRefGoogle Scholar
  16. 16.
    Ray-Coquard I, Weber B, Cretin J, et al. Gemcitabine-oxaliplatin combination for ovarian cancer resistant to taxane-platinum treatment: a phase II study from the GINECO group. Br J Cancer. 2009;100:601–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Stephens AD, Alderman R, Chang D, et al. Morbidity and mortality analysis of 200 treatments with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy using the coliseum technique. Ann Surg Oncol. 1999;6:790–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Elias D, Bonnay A, Puizillou JM, et al. Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution. Ann Oncol. 2002;13:267–72.PubMedCrossRefGoogle Scholar
  19. 19.
    De Somer F, Ceelen W, Delanghe J, et al. Severe hyponatremia, hyperglycemia, and hyperlactatemia are associated with intraoperative hyperthermic intraperitoneal chemoperfusion with oxaliplatin. Perit Dial Int. 2008;28:61–6.PubMedGoogle Scholar
  20. 20.
    Ceelen WP, Peeters M, Houtmeyers P, et al. Safety and efficacy of hyperthermic intraperitoneal chemoperfusion with high-dose oxaliplatin in patients with peritoneal carcinomatosis. Ann Surg Oncol. 2008;15:535–41.PubMedCrossRefGoogle Scholar
  21. 21.
    Eisenkop SM, Friedman RL, Spirtos NM. The role of secondary cytoreductive surgery in the treatment of patients with recurrent epithelial ovarian carcinoma. Cancer. 2000;88:144–53.PubMedCrossRefGoogle Scholar
  22. 22.
    Salani R, Santillan A, Zahurak ML, et al. Secondary cytoreductive surgery for localized, recurrent epithelial ovarian cancer—analysis of prognostic factors and survival outcome. Cancer. 2007;109:685–91.PubMedCrossRefGoogle Scholar
  23. 23.
    Zang RY, Li ZT, Tang J, et al. Secondary cytoreductive surgery for patients with relapsed epithelial ovarian carcinoma: who benefits? Cancer. 2004;100:1152–61.PubMedCrossRefGoogle Scholar
  24. 24.
    Harter P, du Bois A, Hahmann M, et al. Surgery in recurrent ovarian cancer: the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR trial. Ann Surg Oncol. 2006;13:1702–10.PubMedCrossRefGoogle Scholar
  25. 25.
    Ceelen W, Flessner M. Intraperitoneal cytotoxic drug therapy for tumours confined to the peritoneal cavity: biophysical principles and clinical evidence. Nat Rev Clin Oncol. 2009. doi:  10.1038/nrclinonc.2009.217.
  26. 26.
    Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22:3284–92.PubMedCrossRefGoogle Scholar
  27. 27.
    Sugarbaker PH. New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome? Lancet Oncol. 2006;7:69–76.PubMedCrossRefGoogle Scholar
  28. 28.
    Sugarbaker PH. Cytoreductive surgery and perioperative intraperitoneal chemotherapy for the treatment of advanced primary and recurrent ovarian cancer. Curr Opin Obstet Gynecol. 2009;21:15–24.PubMedCrossRefGoogle Scholar
  29. 29.
    Jacquet P, Stephens AD, Averbach AM, et al. Sugarbaker PH. Analysis of morbidity and mortality in 60 patients with peritoneal carcinomatosis treated by cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy. Cancer. 1996;77:2622–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Crawford SC, Vasey PA, Paul J, et al. Does aggressive surgery only benefit patients with less advanced ovarian cancer? Results from an international comparison within the SCOTROC-1 Trial. J Clin Oncol. 2005;23:8802–11.PubMedCrossRefGoogle Scholar
  31. 31.
    Kohandel M, Sivaloganathan S, Oza A. Mathematical modeling of ovarian cancer treatments: sequencing of surgery and chemotherapy. J Theor Biol. 2006;242:62–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Zenasni F, Botella M, Elias D, et al. The long-term impact of hyperthermic intraperitoneal chemotherapy on survivors treated for peritoneal carcinomatosis: a cross-sectional study. Support Care Cancer. 2009;17:1255–61.PubMedCrossRefGoogle Scholar
  33. 33.
    Markman M. Hyperthermic intraperitoneal chemotherapy in the management of ovarian cancer: a critical need for an evidence-based evaluation. Gynecol Oncol. 2009;113:4–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Matei D, Emerson RE, Schilder J, et al. Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis—a Hoosier Oncology Group trial. Cancer. 2008;113:723–32.PubMedCrossRefGoogle Scholar
  35. 35.
    Pietras K, Ostman A, Sjoquist M, et al. Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumors. Cancer Res. 2001;61:2929–34.PubMedGoogle Scholar
  36. 36.
    Zanon C, Clara R, Chiappino I, et al. Cytoreductive surgery and intraperitoneal chemohyperthermia for recurrent peritoneal carcinomatosis from ovarian cancer. World J Surg. 2004;28:1040–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Reichman TW, Cracchiolo B, Sama J, et al. Cytoreductive surgery and intraoperative hyperthermic chemoperfusion for advanced ovarian carcinoma. J Surg Oncol. 2005;90:51–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Rufian S, Munoz-Casares FC, Briceno J, et al. Radical surgery—peritonectomy and intraoperative intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis in recurrent or primary ovarian cancer. J Surg Oncol. 2006;94:316–24.PubMedCrossRefGoogle Scholar
  39. 39.
    Raspagliesi F, Kusamura S, Torres JCC, et al. Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy in advanced/recurrent ovarian cancer patients: the experience of National Cancer Institute of Milan. Eur J Surg Oncol. 2006;32:671–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Helm CW, Toler CR, Martin RS, et al. Cytoreduction and intraperitoneal heated chemotherapy for the treatment of endometrial carcinoma recurrent within the peritoneal cavity. Int J Gynecol Cancer. 2007;17:204–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Di Giorgio A, Naticchioni E, Biacchi D, et al. Cytoreductive surgery (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of diffuse peritoneal carcinomatosis from ovarian cancer. Cancer. 2008;113:315–25.PubMedCrossRefGoogle Scholar
  42. 42.
    Fagotti A, Paris B, Grimolizzi F, et al. Secondary cytoreduction plus oxaliplatin-based HIPEC in platinum-sensitive recurrent ovarian cancer patients: a pilot study. Gynecol Oncol. 2009;113:335–40.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2009

Authors and Affiliations

  • Wim P. Ceelen
    • 1
  • Yves Van Nieuwenhove
    • 1
  • Simon Van Belle
    • 2
  • Hannelore Denys
    • 2
  • Piet Pattyn
    • 1
  1. 1.Department of SurgeryUniversity HospitalGhentBelgium
  2. 2.Department of Medical OncologyUniversity HospitalGhentBelgium

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