Does Intraperitoneal Therapy for Ovarian Cancer Have a Future?

  • Deborah K. Armstrong
  • Michael A. Bookman


Ovarian cancer has a unique pattern of spread, with the majority of disease limited to the peritoneal cavity. Intraperitoneal (IP) delivery of chemotherapeutic agents allows for a higher local concentration of drug for a more prolonged period of time at the major site of disease, providing a rationale for its use in ovarian cancer, although limited by poor penetration of tumor implants. This approach is supported by multiple clinical trials demonstrating improved outcomes for ovarian cancer patients but with uncertainty regarding the optimal selection and scheduling of specific agents. Additional challenges to the adoption of IP therapy include the requirement for initial optimal cytoreductive surgery, experience with catheter placement, staff expertise, and the management of treatment-related toxicity. Nonetheless, the improved survival justifies consideration of IP therapy in appropriate patients. Multiple approaches to decrease toxicity, improve tolerability, and indentify key treatment components are currently being evaluated.


Overall Survival Ovarian Cancer Cytoreductive Surgery Gynecologic Oncology Group Microscopic Residual Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin. 2012;56:106.CrossRefGoogle Scholar
  2. 2.
    du Bois A, Quinn M, Thigpen T, et al. 2004 consensus statements on the management of ovarian cancer: Final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004). Ann Oncol. 2005;16 suppl 8:viii7–12.PubMedGoogle Scholar
  3. 3.
    Cannistra SA. Cancer of the ovary. N Engl J Med. 2004;9(351):2519–29.CrossRefGoogle Scholar
  4. 4.
    Thigpen T. The if and when of surgical debulking for ovarian carcinoma. N Engl J Med. 2004;351:2544–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Fujiwara K, Armstrong DK, Morgan M, Markman M. Principal and practice of intraperitoneal chemotherapy for ovarian cancer. Int J Gynecol Cancer. 2007;17:1–20.PubMedCrossRefGoogle Scholar
  6. 6.
    Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival impact of maximum cytoreductive surgery for advanced ovarian carcinoma during the platinum-era: a meta-analysis of 6,885 patients. J Clin Oncol. 2002;20:1248–59.PubMedCrossRefGoogle Scholar
  7. 7.
    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):CD007565. doi: 10.1002/14651858.CD007565.pub2.
  8. 8.
    Weisenberger AS, Levine B, Storaasli JP. Use of nitrogen mustard in treatment of serous effusions of neoplastic origin. JAMA. 1955;159:1704–7.Google Scholar
  9. 9.
    Speyer JL, Collins JM, Dedrick RL, et al. Phase I and pharmacological studies of 5-fluorouracil administered intraperitoneally. Cancer Res. 1980;40:567–72.PubMedGoogle Scholar
  10. 10.
    Markman M, Cleary S, Lucas WE, Howell SB. Intraperitoneal chemotherapy with high-dose cisplatin and cytosine arabinoside for refractory ovarian carcinoma and other malignancies principally involving the peritoneal cavity. J Clin Oncol. 1985;3:925–31.PubMedGoogle Scholar
  11. 11.
    Dedrick RL, Flessner MF. Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer Inst. 1997;89:480–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Grantab RH, Tannock IF. Penetration of anticancer drugs through tumour tissue as a function of cellular packing density and interstitial fluid pressure and its modification by bortezomib. BMC Cancer. 2012;12:214.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Jandial DD, Messer K, Farshchi-Heydari S, Pu M, Howell SB. Tumor platinum concentration following intraperitoneal administration of cisplatin versus carboplatin in an ovarian cancer model. Gynecol Oncol. 2009;115:362–6.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Minchinton AI, Tannock IF. Drug penetration in solid tumours. Nat Rev Cancer. 2006;6:583–92.PubMedCrossRefGoogle Scholar
  15. 15.
    Markman M. Intraperitoneal chemotherapy. Semin Oncol. 1991;18:248–54.PubMedGoogle Scholar
  16. 16.
    Alberts DS, Liu PY, Hannigan EF, 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
  17. 17.
    McGuire WP, Hoskins WJ, Brady MF, 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;334:1–6.PubMedCrossRefGoogle Scholar
  18. 18.
    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
  19. 19.
    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
  20. 20.
    Jaaback K, Johnson N, Lawrie TA. Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer. Cochrane Database Syst Rev. 2011;(11):CD005340.Google Scholar
  21. 21.
    Ozols RF, Bundy BN, Greer BE, 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;21:3194–200.PubMedCrossRefGoogle Scholar
  22. 22.
    Ozols RF, Bookman MA, Young RC. Intraperitoneal chemotherapy for ovarian cancer. N Engl J Med. 2006;354:1641–3.PubMedCrossRefGoogle Scholar
  23. 23.
    Gore M, du Bois A, Vergote I. Intraperitoneal chemotherapy in ovarian cancer remains experimental. J Clin Oncol. 2006;24:4528–30.PubMedCrossRefGoogle Scholar
  24. 24.
    Armstrong DK, Brady MF. Intraperitoneal therapy for ovarian cancer: a treatment ready for prime time. J Clin Oncol. 2006;24:4531–3.PubMedCrossRefGoogle Scholar
  25. 25.
    Wenzel L, Huang HQ, Armstrong DK, Walker JL, Cella D. Health-related quality of life during and after intraperitoneal versus intravenous chemotherapy for optimally debulked ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007;25:437–43.PubMedCrossRefGoogle Scholar
  26. 26.
    Helm CW. Ports and complications for intraperitoneal chemotherapy delivery. BJOG. 2012;119:150–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Guile MW, Horne AL, Thompson SD, Gardner GJ, Giuntoli RL, Armstrong DK, Bristow RE. Intraperitoneal chemotherapy for stage III ovarian cancer using the Gynecologic Oncology Group protocol 172 intraperitoneal regimen: effect of supportive care using aprepitant and pegfilgrastim on treatment completion rate. Clin Ovarian Cancer. 2008;1:68–71.CrossRefGoogle Scholar
  28. 28.
    Tewari D, Java J, et al. Long-term survival advantage of intraperitoneal chemotherapy treatment in advanced ovarian cancer: An analysis of a Gynecologic Oncology Group ancillary data study. Gynecol Oncol 2013;130:e1–e169.Google Scholar
  29. 29.
    Piccart MJ, Bertelsen K, James K, et al. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst. 2000;92:699–708.PubMedCrossRefGoogle Scholar
  30. 30.
    Howell SB. Pharmacologic principles of intraperitoneal chemotherapy for the treatment of ovarian cancer. Int J Gynecol Cancer. 2008;18 Suppl 1:20–5.PubMedCrossRefGoogle Scholar
  31. 31.
    Los G, Verdegaal EM, Mutsaers PH, McVie JG. Penetration of carboplatin and cisplatin into rat peritoneal tumor nodules after intraperitoneal chemotherapy. Cancer Chemother Pharmacol. 1991;28:159–65.PubMedCrossRefGoogle Scholar
  32. 32.
    Markman M, Reichman B, Hakes T, Rubin S, Lewis Jr JL, Jones W, et al. Evidence supporting the superiority of intraperitoneal cisplatin compared to intraperitoneal carboplatin for salvage therapy of small-volume residual ovarian cancer. Gynecol Oncol. 1993;50:100–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Miyagi Y, Fujiwara K, Kigawa J, Itamochi H, Nagao S, Aotani E, et al. Intraperitoneal carboplatin infusion may be a pharmacologically more reasonable route than intravenous administration as a systemic chemotherapy. A comparative pharmacokinetic analysis of platinum using a new mathematical model after intraperitoneal vs. intravenous infusion of carboplatin—a Sankai Gynecology Study Group (SGSG) study. Gynecol Oncol. 2005;99:591–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Morgan MA, Sill MW, Fujiwara K, et al. A phase I study with an expanded cohort to assess the feasibility of intraperitoneal carboplatin and intravenous paclitaxel in untreated ovarian, fallopian tube, and primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2011;121:264–8.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Katsumata N, Yasuda M, Takahashi F, 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;374:1331–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Seamon LG, Richardson DL, Copeland LJ. Evolution of the Gynecologic Oncology Group protocols in the treatment of epithelial ovarian cancer. Clin Obstet Gynecol. 2012;55:131–55.PubMedCrossRefGoogle Scholar
  37. 37.
    Bristow RE, Zahurak ML, Diaz-Montes TP, Giuntoli RL, Armstrong DK. Impact of surgeon and hospital ovarian cancer surgical case volume on in-hospital mortality and related short-term outcomes. Gynecol Oncol. 2009;115:334–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Havrilesky LJ, Secord AA, Darcy KM, Armstrong DK, Kulasingam S. Cost-effectiveness analysis of intraperitoneal versus intravenous chemotherapy for women with optimally-resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2008;26:4144–50.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Bristow RE, Santillan A, Salani R, et al. Intraperitoneal cisplatin and paclitaxel versus intravenous carboplatin and paclitaxel chemotherapy for stage III ovarian cancer: a cost-effectiveness analysis. Gynecol Oncol. 2007;106:476–81.PubMedCrossRefGoogle Scholar
  40. 40.
    Bookman MA, Brady MF, et al. Evaluation of New Platinum-Based Treatment Regimens in Advanced-Stage Ovarian Cancer: a Phase III trial of the Gynecologic Cancer InterGroup (GCIG). J Clin Oncol 2009;27:1419–25.Google Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.Medical OncologyJohns Hopkins Kimmel Cancer Center, The Johns Hopkins HospitalBaltimoreUSA
  2. 2.Division of Hematology-OncologyUniversity of Arizona Cancer CenterTucsonUSA

Personalised recommendations