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

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 Access through your institution Buy or subscribe This is a preview of subscription content,

access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn

more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS

OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS PROPHYLACTIC HYPERTHERMIC INTRAPERITONEAL

CHEMOTHERAPY MAY BENEFIT THE LONG-TERM SURVIVAL OF PATIENTS AFTER RADICAL GASTRIC CANCER SURGERY Article Open access 16 February 2022 PRIMARY AND METASTATIC PERITONEAL SURFACE MALIGNANCIES

Article 16 December 2021 ADVANCES IN THE MANAGEMENT OF PERITONEAL MALIGNANCIES Article 07 September 2022 REFERENCES * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  *

Flessner, M. F. Endothelial glycocalyx and the peritoneal barrier. _Perit. Dial. Int._ 28, 6–12 (2008). PubMed  Google Scholar  * 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  * Dedrick, R. L. Theoretical and experimental bases of

intraperitoneal chemotherapy. _Semin. Oncol._ 12, 1–6 (1985). CAS  PubMed  Google Scholar  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * Minchinton, A. I. & Tannock, I. F. Drug penetration in solid tumors. _Nat. Rev. Cancer_ 6, 583–592 (2006). Article 

CAS  PubMed  Google Scholar  * 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  * 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  * 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  * 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  * 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  * DeVita, V. T. Let's return to the “belly bath”. _Nat. Clin. Pract. Oncol._ 3, 405 (2006). Article  PubMed  Google Scholar  * 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  *

Issels, R. D. Hyperthermia adds to chemotherapy. _Eur. J. Cancer_ 44, 2546–2554 (2008). Article  CAS  PubMed  Google Scholar  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  *

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  * 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

  * 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  * US National Insitutes of Health _Intraperitoneal chemotherapy for ovarian cancer_. http://ctep.cancer.gov/highlights/docs/clin_annc_010506.pdf

(2009). * 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  * 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  * 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  * 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  * 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  * 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  * 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  * Ryu, K. S. _ et

al_. Effects of intraperitoneal hyperthermic chemotherapy in ovarian cancer. _Gynecol. Oncol._ 94, 325–332 (2004). Article  CAS  PubMed  Google Scholar  * 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  * 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  * 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 

* Smeenk, R. M., Verwaal, V. J. & Zoetmulder, F. A. N. _Pseudomyxoma peritonei_. _Cancer Treatment Rev._ 33, 138–145 (2007). Article  CAS  Google Scholar  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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 

* 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  * 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  * 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  *

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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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 * Department of Surgery, University Hospital, De Pintelaan 185, B-9000, Ghent, Belgium Wim P. Ceelen * Department of Medicine, University of Mississippi

Medical Center, 2500 North State Street, Jackson, 39216, MS, USA Michael F. Flessner Authors * Wim P. Ceelen View author publications You can also search for this author inPubMed Google

Scholar * Michael F. Flessner View author publications You can also search for this author inPubMed Google Scholar 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: 15 December 2009 * Issue Date: February 2010 * DOI: https://doi.org/10.1038/nrclinonc.2009.217 SHARE THIS ARTICLE Anyone you share the following link with will be able to read

this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative