Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Intraperitoneal therapy for peritoneal tumors: biophysics and clinical evidence

Abstract

In patients with tumors confined to the peritoneal cavity, there is established pharmacokinetic and tumor biology-related evidence that intraperitoneal drug administration is advantageous. Three large randomized trials in patients with stage III ovarian cancer who underwent optimal cytoreduction have demonstrated a significant survival benefit when intraperitoneal chemotherapy was added to systemic therapy. Although intraperitoneal therapy is associated with locoregional toxic effects, recent trials suggest that with some modification of the local delivery methods this approach is safe in 80% of patients in an ambulatory setting. Surgical cytoreduction immediately followed by intraoperative hyperthermic intraperitoneal chemoperfusion (HIPEC) ensures intraperitoneal delivery of the drug to all peritoneal surfaces and the advantages of combined hyperthermia to be exploited. An increasing number of centers are initiating this multimodality therapy in ovarian cancer and colorectal cancer. Clearly, intraperitoneal drug delivery is an important adjunct to surgery and systemic chemotherapy in selected patients. The optimal drug, dose and schedule for intraperitoneal delivery, the exact role of added HIPEC compared with cytoreduction alone, and the potential role of HIPEC in ovarian cancer and peritoneal mesothelioma are still undefined. Several randomized controlled trials addressing these uncertainties have been initiated.

Key Points

  • Intraperitoneal drug delivery has proven efficacy in patients with minimal or microscopic residual disease following surgery

  • In large randomized trials a significant improvement in outcome of stage III ovarian cancer was demonstrated when intraperitoneal platinum-based chemotherapy was added to systemic therapy

  • Methodological issues concerning these trials and locoregional toxic effects have prevented widespread adoption of intraperitoneal chemotherapy in ovarian cancer

  • Surgical cytoreduction immediately followed by intraoperative hyperthermic intraperitoneal chemoperfusion (HIPEC) ensures intraperitoneal delivery of the drug to all peritoneal surfaces at risk

  • Cytoreduction and HIPEC are optimal therapies for mucinous appendiceal tumors; one randomized trial showed a superior outcome of the combined approach versus palliation in peritoneal metastases from colorectal cancer

  • The potential of HIPEC as an adjunct to surgery in ovarian cancer and peritoneal mesothelioma is promising but has not been demonstrated in controlled randomized trials

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic representation of drug penetration into peritoneal tumors.

Similar content being viewed by others

References

  1. Warrick, C. An improvement on the practice of tapping; whereby that operation, instead of a relief for symptoms, becomes an absolute cure for an ascites, exemplified in the case of Jane Roman; and recommended to the consideration of the Royal Society, by Christopher Warrick, of Truro, Surgeon. Philos. Trans. R. Soc. Lond. B. Biol. Sci 43, 12–19 (1744).

    Article  Google Scholar 

  2. Weisberger, A. S., Levine, B. & Storaasli, J. P. Use of nitrogen mustard in treatment of serous effusions of neoplastic origin. J. Am. Med. Assoc. 159, 1704–1707 (1955).

    Article  CAS  PubMed  Google Scholar 

  3. Dedrick, R. L., Myers, C. E., Bungay, P. M. & DeVita, V. T. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat. Rep. 62, 1 (1978).

    CAS  PubMed  Google Scholar 

  4. Markman, M. Strategies to examine new compounds for intraperitoneal use in ovarian cancer. Int. J. Gynecol. Cancer 18, 33–35 (2008).

    Article  PubMed  Google Scholar 

  5. Li, X. F. et al. Visualization of hypoxia in microscopic tumors by immunofluorescent microscopy. Cancer Res. 67, 7646–7653 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Jakobsen, A. & Mortensen, L. S. On the importance of sensitivity to the dose-effect relationship in chemotherapy. Acta Oncol. 36, 375–381 (1997).

    Article  CAS  PubMed  Google Scholar 

  7. Alberts, D. S., Young, L., Mason, N. & Salmon, S. E. In vitro evaluation of anticancer drugs against ovarian cancer at concentrations achievable by intraperitoneal administration. Semin. Oncol. 12, 38–42 (1985).

    CAS  PubMed  Google Scholar 

  8. Andrews, P. A., Velury, S., Mann, S. C. & Howell, S. B. Cis-Diamminedichloroplatinum(Ii) accumulation in sensitive and resistant human ovarian carcinoma sells. Cancer Res. 48, 68–73 (1988).

    CAS  PubMed  Google Scholar 

  9. Matsushima, Y. et al. Time-schedule dependency of the inhibiting activity of various anticancer drugs in the clonogenic assay. Cancer Chemother. Pharmacol. 14, 104–107 (1985).

    Article  CAS  PubMed  Google Scholar 

  10. Flessner, M., Henegar, J., Bigler, S. & Genous, L. Is the peritoneum a significant transport barrier in peritoneal dialysis? Perit. Dial. Int. 23, 542–549 (2003).

    CAS  PubMed  Google Scholar 

  11. Vazquez, V. D., Stuart, O. A., Mohamed, F. & Sugarbaker, P. Extent of parietal peritonectomy does not change intraperitoneal chemotherapy pharmacokinetics. Cancer Chemother. Rep. 52, 108–112 (2003).

    Article  CAS  Google Scholar 

  12. Flessner, M. F. Endothelial glycocalyx and the peritoneal barrier. Perit. Dial. Int. 28, 6–12 (2008).

    PubMed  Google Scholar 

  13. Howell, S. B. Pharmacologic principles of intraperitoneal chemotherapy for the treatment of ovarian cancer. Int. J. Gynecol. Cancer 18, 20–25 (2008).

    Article  PubMed  Google Scholar 

  14. Dedrick, R. L. Theoretical and experimental bases of intraperitoneal chemotherapy. Semin. Oncol. 12, 1–6 (1985).

    CAS  PubMed  Google Scholar 

  15. Dedrick, R. L., Flessner, M. F., Collins, J. M. & Schultz, J. S. Is the peritoneum a membrane? Am. Soc. Artificial Intern. Organs J. 5, 1–5 (1982).

    Article  Google Scholar 

  16. Flessner, M. F., Dedrick, R. L. & Schultz, J. S. A distributed model of peritoneal-plasma transport: theoretical consideratons. Am. J. Physiol. 246, R597–R607 (1984).

    CAS  PubMed  Google Scholar 

  17. Heldin, C. H., Rubin, K., Pietras, K. & Ostman, A. High interstitial fluid pressure—an obstacle in cancer therapy. Nat. Rev. Cancer 4, 806–813 (2004).

    Article  CAS  PubMed  Google Scholar 

  18. Flessner, M. F., Choi, J., Credit, K., Deverkadra, R. & Henderson, K. Resistance of tumor interstitial pressure to the penetration of intraperitoneally delivered antibodies into metastatic ovarian tumors. Clin. Cancer Res. 11, 3117–3125 (2005).

    Article  CAS  PubMed  Google Scholar 

  19. Holzer, A. K. et al. The copper influx transporter human copper transport protein 1 regulates the uptake of cisplatin in human ovarian carcinoma cells. Mol. Pharmacol. 66, 817–823 (2004).

    Article  CAS  PubMed  Google Scholar 

  20. Holzer, A. K., Katano, K., Clomp, L. W. J. & Howell, S. B. Cisplatin rapidly down-regulates its own influx transporter hCTR1 in cultured human ovarian carcinoma cells. Clin. Cancer Res. 10, 6744–6749 (2004).

    Article  CAS  PubMed  Google Scholar 

  21. Nederman, T. & Carlsson, J. Penetration and binding of vinblastine and 5-fluorouracil in cellular spheroids. Cancer Chemother. Pharmacol. 13, 131–135 (1984).

    Article  CAS  PubMed  Google Scholar 

  22. van de Vaart, P. J. M. et al. Intraperitoneal cisplatin with regional hyperthermia in advanced ovarian cancer: Pharmacokinetics and cisplatin-DNA adduct formation in patients and ovarian cancer cell lines. Eur. J. Cancer 34, 148–154 (1998).

    Article  CAS  PubMed  Google Scholar 

  23. Minchinton, A. I. & Tannock, I. F. Drug penetration in solid tumors. Nat. Rev. Cancer 6, 583–592 (2006).

    Article  CAS  PubMed  Google Scholar 

  24. Primeau, A. J., Rendon, A., Hedley, D., Lilge, L. & Tannock, I. F. The distribution of the anticancer drug doxorubicin in relation to blood vessels in solid tumors. Clin. Cancer Res. 11, 8782–8788 (2005).

    Article  CAS  PubMed  Google Scholar 

  25. Jang, S. H., Wientjes, M. G. & Au, J. L. S. Enhancement of paclitaxel delivery to solid tumors by apoptosis-inducing pretreatment: Effect of treatment schedule. J. Pharmacol. Exp. Ther. 296, 1035–1042 (2001).

    CAS  PubMed  Google Scholar 

  26. Kondo, A. et al. Hypotonic intraperitoneal cisplatin chemotherapy for peritoneal carcinomatosis in mice. Br. J. Cancer 73, 1166–1170 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Esquis, P. et al. High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis. Ann. Surg. 244, 106–112 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Jones, R. B. et al. High volume intraperitoneal chemotherapy with methotrexate in patients with cancer. Cancer Res. 41, 55–59 (1981).

    CAS  PubMed  Google Scholar 

  29. DeVita, V. T. Let's return to the “belly bath”. Nat. Clin. Pract. Oncol. 3, 405 (2006).

    Article  PubMed  Google Scholar 

  30. Spratt, J. S., Adcock, R. A., Muskovin, M., Sherrill, W. & Mckeown, J. Clinical delivery system for intra-peritoneal hyperthermic chemotherapy. Cancer Res. 40, 256–260 (1980).

    CAS  PubMed  Google Scholar 

  31. Issels, R. D. Hyperthermia adds to chemotherapy. Eur. J. Cancer 44, 2546–2554 (2008).

    Article  CAS  PubMed  Google Scholar 

  32. Sun, X. R. et al. Changes in tumor hypoxia induced by mild temperature hyperthermia as assessed by dual-tracer immunohistochemistry. Radiother. Oncol. 88, 269–276 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Los, G. et al. Optimization of intraperitoneal cisplatin therapy with regional hyperthermia in rats. Eur. J. Cancer 27, 472–477 (1991).

    Article  CAS  PubMed  Google Scholar 

  34. Los, G. et al. A rationale for carboplatin treatment and abdominal hyperthermia in cancers restricted to the peritoneal cavity. Cancer Res. 52, 1252–1258 (1992).

    CAS  PubMed  Google Scholar 

  35. Pestieau, S. R., Belliveau, J. F., Griffin, H., Stuart, O. A. & Sugarbaker, P. H. Pharmacokinetics of intraperitoneal oxaliplatin: Experimental studies. J. Surg. Oncol. 76, 106–114 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Jacquet, P., Averbach, A., Stuart, O. A., Chang, D. & Sugarbaker, P. H. Hyperthermic intraperitoneal doxorubicin: pharmacokinetics, metabolism, and tissue distribution in a rat model. Cancer Chemother. Pharmacol. 41, 147–154 (1998).

    Article  CAS  PubMed  Google Scholar 

  37. Yan, T. D., Black, D., Savady, R. & Sugarbaker, P. H. Systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma. J. Clin. Oncol. 24, 4011–4019 (2006).

    Article  PubMed  Google Scholar 

  38. Markman, M. et al. Responses to second-line cisplatin-based intraperitoneal therapy in ovarian cancer: influence of a prior response to intravenous cisplatin. J. Clin. Oncol. 9, 1801–1805 (1991).

    Article  CAS  PubMed  Google Scholar 

  39. Markman, M. et al. Evidence supporting the superiority of intraperitoneal cisplatin compared to intraperitoneal carboplatin for salvage therapy of small-volume residual ovarian cancer. Gynecol. Oncol. 50, 100–104 (1993).

    Article  CAS  PubMed  Google Scholar 

  40. Gadducci, A. & Conte, P. F. Intraperitoneal chemotherapy in the management of patients with advanced epithelial ovarian cancer: a critical review of the literature. Int. J. Gynecol. Cancer 18, 943–953 (2008).

    Article  CAS  PubMed  Google Scholar 

  41. Juretzka, M. M. et al. CA125 level as a predictor of progression-free survival and overall survival in ovarian cancer patients with surgically defined disease status prior to the initiation of intraperitoneal consolidation therapy. Gynecol. Oncol. 104, 176–180 (2007).

    Article  CAS  PubMed  Google Scholar 

  42. Francis, P. et al. Phase I feasibility and pharmacological study of weekly intraperitoneal paclitaxel: a Gynecologic Oncology Group pilot study. J. Clin. Oncol. 13, 2961–2967 (1995).

    Article  CAS  PubMed  Google Scholar 

  43. US National Insitutes of Health Intraperitoneal chemotherapy for ovarian cancer. http://ctep.cancer.gov/highlights/docs/clin_annc_010506.pdf (2009).

  44. Kyrgiou, M., Salanti, G., Pavlidis, N., Paraskevaidis, E. & Ioannidis, J. P. A. Survival benefits with diverse chemotherapy regimens for ovarian cancer: Meta-analysis of multiple treatments. J. Natl Cancer Inst. 98, 1655–1663 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. Vergote, I. et al. Intraperitoneal chemotherapy in patients with advanced ovarian cancer: The con view. Oncologist 13, 410–414 (2008).

    Article  CAS  PubMed  Google Scholar 

  46. Ceelen, W. P. & Bracke, M. E. Peritoneal minimal residual disease in colorectal cancer: mechanisms, prevention, and treatment. Lancet Oncol. 10, 72–79 (2009).

    Article  PubMed  Google Scholar 

  47. Hribaschek, A. et al. Comparison of intraperitoneal with intravenous administration of taxol in experimental peritoneal carcinomatosis. Chemotherapy 53, 410–417 (2007).

    Article  CAS  PubMed  Google Scholar 

  48. Vaillant, J. C. et al. Adjuvant intraperitoneal 5-fluorouracil in high-risk colon cancer: A multicenter phase III trial. Ann. Surg. 231, 449–456 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Nordlinger, B. et al. Adjuvant regional chemotherapy and systemic chemotherapy versus systemic chemotherapy alone in patients with stage II–III colorectal cancer: a multicentre randomised controlled phase III trial. Lancet Oncol. 6, 459–468 (2005).

    Article  CAS  PubMed  Google Scholar 

  50. Cotte, E. et al. Cytoreductive surgery and intraperitoneal chemohyperthermia for chemoresistant and recurrent advanced epithelial ovarian cancer: Prospective study of 81 patients. World J. Surg. 31, 1813–1821 (2007).

    Article  PubMed  Google Scholar 

  51. Ryu, K. S. et al. Effects of intraperitoneal hyperthermic chemotherapy in ovarian cancer. Gynecol. Oncol. 94, 325–332 (2004).

    Article  CAS  PubMed  Google Scholar 

  52. Bijelic, L., Jonson, A. & Sugarbaker, P. H. Systematic review of cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis in primary and recurrent ovarian cancer. Ann. Oncol. 18, 1943–1950 (2007).

    Article  CAS  PubMed  Google Scholar 

  53. Markman, M. Hyperthermic intraperitoneal chemotherapy in the management of ovarian cancer: a critical need for an evidence-based evaluation. Gynecol. Oncol. (in press) doi: 10.1016/j.ygyno.2008.12.022.

    Article  PubMed  Google Scholar 

  54. Pai, R. K. & Longacre, T. A. Appendiceal mucinous tumors and pseudomyxoma peritonei: histologic features, diagnostic problems, and proposed classification. Adv. Anat. Pathol. 12, 291–311 (2005).

    Article  PubMed  Google Scholar 

  55. Smeenk, R. M., Verwaal, V. J. & Zoetmulder, F. A. N. Pseudomyxoma peritonei. Cancer Treatment Rev. 33, 138–145 (2007).

    Article  CAS  Google Scholar 

  56. Sugarbaker, P. H. & Chang, D. Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy. Ann. Surg. Oncol. 6, 727–731 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. Elias, D. et al. Peritoneal pseudomyxoma: results of a systematic policy of complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Br. J. Surg. 95, 1164–1171 (2008).

    Article  CAS  PubMed  Google Scholar 

  58. Smeenk, R. M., Verwaal, V. J., Antonini, N. & Zoetmulder, F. A. N. Survival analysis of pseudomyxoma peritonei patients treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann. Surg. 245, 104–109 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Sugarbaker, P. H. New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome? Lancet Oncol. 7, 69–76 (2006).

    Article  PubMed  Google Scholar 

  60. Miner, T. J. et al. Long-term survival following treatment of pseudomyxoma peritonei: an analysis of surgical therapy. Ann. Surg. 241, 300–308 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Jayne, D. G., Fook, S., Loi, C. & Seow-Choen, F. Peritoneal carcinomatosis from colorectal cancer. Br. J. Surg. 89, 1545–1550 (2002).

    Article  CAS  PubMed  Google Scholar 

  62. Glehen, O. 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. 22, 3284–3292 (2004).

    Article  CAS  PubMed  Google Scholar 

  63. Verwaal, V. J., Bruin, S., Boot, H., van Slooten, G. & van Tinteren, H. 8-year follow-up of randomized trial: Cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann. Surg. Oncol. 15, 2426–2432 (2008).

    Article  PubMed  Google Scholar 

  64. Verwaal, V. J. et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J. Clin. Oncol. 21, 3737–3743 (2003).

    Article  PubMed  Google Scholar 

  65. Jacquet, P. & Sugarbaker, P. H. Current methodologies for clinical assessment of patients with peritoneal carcinomatosis. J. Exp. Clin. Cancer Res. 15, 49–58 (1996).

    Google Scholar 

  66. Swellengrebel, H. A. M., Verwaal, V. J., Smeenk, R. M., Antonini, N. & Zoetmulder, F. A. N. Quantitative intra-operative assessment of peritoneal carcinomatosis—a comparison of three prognostic tools. 14th European Cancer Conference (ECCO 14) 3072 (Pergamon-Elsevier Science Ltd, Barcelona, Spain, 2007).

    Google Scholar 

  67. Kohne, C. H. et al. Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients. Ann. Oncol. 13, 308–317 (2002).

    Article  CAS  PubMed  Google Scholar 

  68. Folprecht, G. et al. Effect of systemic chemotherapy (CTx) in patients with known peritoneal carcinomatosis (PC) from colorectal cancer [abstract 294]. ASCO Gastrointestinal Cancers Symposium (2007).

    Google Scholar 

  69. Elias, D. et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J. Clin. Oncol. 27, 681–685 (2009).

    Article  PubMed  Google Scholar 

  70. Yan, T. D., Welch, L., Black, D. & Sugarbaker, P. H. A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma. Ann. Oncol. 18, 827–834 (2007).

    Article  CAS  PubMed  Google Scholar 

  71. Yan, T. D. et al. A systematic review and meta-analysis of the randomized controlled trials on adjuvant intraperitoneal chemotherapy for resectable gastric cancer. Ann. Surg. Oncol. 14, 2702–2713 (2007).

    Article  PubMed  Google Scholar 

  72. Rao, G., Crispens, M. & Rothenberg, M. L. Intraperitoneal chemotherapy for ovarian cancer: Overview and perspective. J. Clin. Oncol. 25, 2867–2872 (2007).

    Article  CAS  PubMed  Google Scholar 

  73. Chin, S. N. et al. Evaluation of an intraperitoneal chemotherapy program implemented at the Princess Margaret Hospital for patients with epithelial ovarian carcinoma. Gynecol. Oncol. 112, 450–454 (2009).

    Article  CAS  PubMed  Google Scholar 

  74. Smeenk, R. M., Verwaal, V. J. & Zoetmulder, F. A. N. Toxicity and mortality of cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei—a report of 103 procedures. Eur. J. Surg. Oncol. 32, 186–190 (2006).

    Article  CAS  PubMed  Google Scholar 

  75. Verwaal, V. J., Van Tinteren, H., Ruth, S. V. & Zoetmulder, F. A. N. Toxicity of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. J. Surg. Oncol. 85, 61–67 (2004).

    Article  PubMed  Google Scholar 

  76. Ceelen, W. P. et al. Safety and efficacy of hyperthermic intraperitoneal chemoperfusion with high-dose oxaliplatin in patients with peritoneal carcinomatosis. Ann. Surg. Oncol. 15, 535–541 (2008).

    Article  PubMed  Google Scholar 

  77. Shimizu, T., Maeta, M. & Koga, S. Influence of local hyperthermia on the Healing of small intestinal anastomoses in the rat. Br. J. Surg. 78, 57–59 (1991).

    Article  CAS  PubMed  Google Scholar 

  78. Pelz, J. O. W. et al. Hyperthermic intraperitoneal chemoperfusion (HIPEC) decrease wound strength of colonic anastomosis in a rat model. Intl J. Colorect. Dis. 22, 941–947 (2007).

    Article  CAS  Google Scholar 

  79. Jacquet, P. et al. Analysis of morbidity and mortality in 60 patients with peritoneal carcinomatosis treated by cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy. Cancer 77, 2622–2629 (1996).

    Article  CAS  PubMed  Google Scholar 

  80. Alberts, D. S. et al. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N. Engl. J. Med. 335, 1950–1955 (1996).

    Article  CAS  PubMed  Google Scholar 

  81. Markman, M. 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. 19, 1001–1007 (2001).

    Article  CAS  PubMed  Google Scholar 

  82. Armstrong, D. K. et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N. Engl. J. Med. 354, 34–43 (2006).

    Article  CAS  PubMed  Google Scholar 

  83. Fujimoto, S. et al. Cytohistologic assessment of antitumor effects of intraperitoneal hyperthermic perfusion with mitomycin C for patients with gastric cancer with peritoneal metastasis. Cancer 70, 2754–2760 (1992).

    Article  CAS  PubMed  Google Scholar 

  84. van de Vaart, P. J. M. et al. Intraperitoneal cisplatin with regional hyperthermia in advanced ovarian cancer: Pharmacokinetics and cisplatin-DNA adduct formation in patients and ovarian cancer cell lines. Eur. J. Cancer 34, 148–154 (1998).

    Article  CAS  PubMed  Google Scholar 

  85. Los, G. et al. A rationale for carboplatin treatment and abdominal hyperthermia in cancers restricted to the peritoneal cavity. Cancer Res. 52, 1252–1258 (1992).

    CAS  PubMed  Google Scholar 

  86. Elias, D. et al. Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution. Ann. Oncol. 13, 267–272 (2002).

    Article  CAS  PubMed  Google Scholar 

  87. Kuh, H. J., Jang, S. H., Wientjes, M. G., Weaver, J. R. & Au, J. L. S. Determinants of paclitaxel penetration and accumulation in human solid tumor. J. Pharmacol. Exp. Ther. 290, 871–880 (1999).

    CAS  PubMed  Google Scholar 

  88. Morgan, R. J. et al. Phase I trial of intraperitoneal gemcitabine in the treatment of advanced malignancies primarily confined to the peritoneal cavity. Clin. Cancer Res. 13, 1232–1237 (2007).

    Article  CAS  PubMed  Google Scholar 

  89. Wiedemann, G., Mella, O., Roszinski, S., Weiss, C. & Wagner, T. Hyperthermia enhances mitoxantrone cytotoxicity on human breast carcinoma and sarcoma xenografts in nude mice. Int. J. Radiat. Oncol. Biol. Phys. 24, 669–673 (1992).

    Article  CAS  PubMed  Google Scholar 

  90. Jacquet, P., Averbach, A., Stuart, O. A., Chang, D. & Sugarbaker, P. H. Hyperthermic intraperitoneal doxorubicin: pharmacokinetics, metabolism, and tissue distribution in a rat model. Cancer Chemother. Pharmacol. 41, 147–154 (1998).

    Article  CAS  PubMed  Google Scholar 

  91. Harada, S. et al. The antitumor effect of hyperthermia combined with fluorouracil and its analogues. Radiat. Res. 142, 232–241 (1995).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wim P. Ceelen.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ceelen, W., Flessner, M. Intraperitoneal therapy for peritoneal tumors: biophysics and clinical evidence. Nat Rev Clin Oncol 7, 108–115 (2010). https://doi.org/10.1038/nrclinonc.2009.217

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrclinonc.2009.217

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing