Intraperitoneal chemotherapy for treatment of ovarian cancer
- Maurie Markman, MD
Maurie Markman, MD
- Clinical Professor of Medicine
- Drexel University College of Medicine
- President, Medicine & Science
- Cancer Treatment Centers of America
- Alexander B Olawaiye, MD
Alexander B Olawaiye, MD
- Associate Professor of Obstetrics, Gynecology and Reproductive Sciences
- University of Pittsburgh
- Section Editors
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Don S Dizon, MD, FACP
Don S Dizon, MD, FACP
- Section Editor – Gynecologic Oncology
- Clinical Co-Director, Gynecologic Oncology
- Founder and Director, The Oncology Sexual Health Clinic
- Massachusetts General Hospital Cancer Center
- Associate Professor of Medicine
- Harvard Medical School
- Deputy Editors
- Sadhna R Vora, MD
Sadhna R Vora, MD
- Deputy Editor — Oncology
- Instructor in Medicine
- Harvard Medical School
- Sandy J Falk, MD, FACOG
Sandy J Falk, MD, FACOG
- Director, Editorial Relations — UpToDate
- Deputy Editor — Obstetrics, Gynecology and Women's Health
- Instructor of Obstetrics, Gynecology and Reproductive Biology, Part-time
- Harvard Medical School
The most common route of ovarian cancer spread is within the peritoneal cavity. The rationale for administering chemotherapy directly into the peritoneal cavity is supported by preclinical, pharmacokinetic, and pharmacodynamics data. Compared with intravenous (IV) treatment, intraperitoneal (IP) administration permits a several-fold increase in drug concentration to be achieved within the abdominal cavity. In addition, clinical trials have demonstrated a survival advantage to the incorporation of IP treatment in the upfront management of ovarian cancer.
The rationale and technical issues related to IP chemotherapy for ovarian cancer will be reviewed here. A more extensive discussion on the data to support the use of IP treatment in ovarian cancer is covered separately. (See "Cancer of the ovary, fallopian tube, and peritoneum: Staging and initial surgical management" and "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tubal, and peritoneal cancer".)
In the vast majority of patients, epithelial ovarian cancer (EOC, which includes fallopian tube and peritoneal cancers) is confined to the peritoneal cavity at initial diagnosis and in recurrence . Because of this natural history, ovarian cancer is an ideal target for intraperitoneal (IP) therapy. Pharmacokinetic studies have demonstrated that IP administration of chemotherapy results in high peritoneal to plasma ratios for peak concentration for cisplatin, paclitaxel, carboplatin, and docetaxel . The higher peritoneal concentration is hypothesized to improve efficacy by increasing concentration of the cytotoxic agent in the tumor microenvironment. Analysis of intratumoral drug concentrations demonstrates that lesions 2 to 3 mm or smaller will have significantly higher drug exposure from intraperitoneal administration as compared with intravenous administration . In addition, avascular tumors are exposed to higher drug concentrations with intraperitoneal compared with intravenous delivery, while systemic exposure and associated toxicity is minimized [4,5]. (See "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tubal, and peritoneal cancer", section on 'Women with optimally cytoreduced disease'.)
Indications for IP chemotherapy — Based on available clinical data, intraperitoneal (IP) chemotherapy may be most useful in women with optimally debulked (to ≤1.0 cm) stage III epithelial ovarian cancer (EOC). Some patients with earlier-stage disease may also be candidates (see "Adjuvant therapy of early stage (stage I and II) epithelial ovarian, fallopian tubal, or peritoneal cancer", section on 'Selection of patients'). Those patients who have been cytoreduced to no gross residual disease seem to have the greatest benefit from IP chemotherapy and improved overall survival.
Furthermore, some experts also utilize IP chemotherapy for women treated with neoadjuvant chemotherapy who undergo an optimal interval cytoreduction. However, there are no prospective data to evaluate this strategy, and we await data from the OV.21 trial to inform this decision . The management and choice of chemotherapy for EOC is discussed separately. (See "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tubal, and peritoneal cancer".)
- Helm CW. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer. Oncologist 2009; 14:683.
- Markman M. Intraperitoneal chemotherapy in the management of malignant disease. Expert Rev Anticancer Ther 2001; 1:142.
- Los G, Mutsaers PH, Lenglet WJ, et al. Platinum distribution in intraperitoneal tumors after intraperitoneal cisplatin treatment. Cancer Chemother Pharmacol 1990; 25:389.
- Dedrick RL, Myers CE, Bungay PM, DeVita VT Jr. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep 1978; 62:1.
- Balthasar JP, Fung HL. Pharmacokinetic and pharmacodynamic optimization of intraperitoneal chemotherapy. Life Sci 1996; 58:535.
- Mackay HJ, Provencheur D, Heywood M, et al. Phase ii/iii study of intraperitoneal chemotherapy after neoadjuvant chemotherapy for ovarian cancer: ncic ctg ov.21. Curr Oncol 2011; 18:84.
- 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.
- Markman M, Hakes T, Reichman B, et al. Intraperitoneal cisplatin and cytarabine in the treatment of refractory or recurrent ovarian carcinoma. J Clin Oncol 1991; 9:204.
- Guastalla JP, Vermorken JB, Wils JA, et al. Phase II trial for intraperitoneal cisplatin plus intravenous sodium thiosulphate in advanced ovarian carcinoma patients with minimal residual disease after cisplatin-based chemotherapy--a phase II study of the EORTC Gynaecological Cancer Cooperative Group. Eur J Cancer 1994; 30A:45.
- Braly PS, Berek JS, Blessing JA, et al. Intraperitoneal administration of cisplatin and 5-fluorouracil in residual ovarian cancer: a Phase II Gynecologic Oncology Group trial. Gynecol Oncol 1995; 56:164.
- Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006; 354:34.
- 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.
- Jaaback K, Johnson N. Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer. Cochrane Database Syst Rev 2006; :CD005340.
- Hess LM, Benham-Hutchins M, Herzog TJ, et al. A meta-analysis of the efficacy of intraperitoneal cisplatin for the front-line treatment of ovarian cancer. Int J Gynecol Cancer 2007; 17:561.
- Fujiwara K, Nagao S, Kigawa J, et al. Phase II study of intraperitoneal carboplatin with intravenous paclitaxel in patients with suboptimal residual epithelial ovarian or primary peritoneal cancer: a Sankai Gynecology Cancer Study Group Study. Int J Gynecol Cancer 2009; 19:834.
- Fujiwara K, Aotani E, Hamano T, et al. A randomized Phase II/III trial of 3 weekly intraperitoneal versus intravenous carboplatin in combination with intravenous weekly dose-dense paclitaxel for newly diagnosed ovarian, fallopian tube and primary peritoneal cancer. Jpn J Clin Oncol 2011; 41:278.
- Walker JL, Armstrong DK, Huang HQ, et al. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group Study. Gynecol Oncol 2006; 100:27.
- Makhija S, Leitao M, Sabbatini P, et al. Complications associated with intraperitoneal chemotherapy catheters. Gynecol Oncol 2001; 81:77.
- Kothari R, Nagel C, Koopmeiners JS, et al. The effect of age on the tolerability of intraperitoneal chemotherapy, complication rate, and survival in patients with ovarian cancer. Gynecol Oncol 2010; 119:491.
- Markman M, Walker JL. Intraperitoneal chemotherapy of ovarian cancer: a review, with a focus on practical aspects of treatment. J Clin Oncol 2006; 24:988.
- Liou WS, Teng NN, Chan JK. A modified technique for insertion of intraperitoneal port for chemotherapy. J Surg Oncol 2005; 90:247.
- Ivy JJ, Geller M, Pierson SM, et al. Outcomes associated with different intraperitoneal chemotherapy delivery systems in advanced ovarian carcinoma: a single institution's experience. Gynecol Oncol 2009; 114:420.
- Rinaldi S, Sera F, Verrina E, et al. The Italian Registry of Pediatric Chronic Peritoneal Dialysis: a ten-year experience with chronic peritoneal dialysis catheters. Perit Dial Int 1998; 18:71.
- Whitney CW. Gynecologic Oncology Group Surgical Procedures Manual. July 2005.
- Marth C, Walker JL, Barakat RR, et al. Results of the 2006 Innsbruck International Consensus Conference on intraperitoneal chemotherapy in patients with ovarian cancer. Cancer 2007; 109:645.
- Topuz E, Salihoglu Y, Aydiner A, et al. Celsite port and catheter as an intraperitoneal access device in the treatment of ovarian cancer. J Surg Oncol 2000; 74:223.
- Landrum LM, Gold MA, Moore KN, et al. Intraperitoneal chemotherapy for patients with advanced epithelial ovarian cancer: a review of complications and completion rates. Gynecol Oncol 2008; 108:342.
- Kehoe SM, Williams NL, Yakubu R, et al. Incidence of intestinal obstruction following intraperitoneal chemotherapy for ovarian tubal and peritoneal malignancies. Gynecol Oncol 2009; 113:228.
- Seewaldt VL, Cain JM, Goff BA, et al. A retrospective review of paclitaxel-associated gastrointestinal necrosis in patients with epithelial ovarian cancer. Gynecol Oncol 1997; 67:137.
- Rose PG, Piver MS. Intestinal perforation secondary to paclitaxel. Gynecol Oncol 1995; 57:270.
- Sakuragi N, Nakajima A, Nomura E, et al. Complications relating to intraperitoneal administration of cisplatin or carboplatin for ovarian carcinoma. Gynecol Oncol 2000; 79:420.
- Bristow RE, Tomacruz RS, Armstrong DK, et al. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 2002; 20:1248.
- Carney ME, Lancaster JM, Ford C, et al. A population-based study of patterns of care for ovarian cancer: who is seen by a gynecologic oncologist and who is not? Gynecol Oncol 2002; 84:36.
- Bristow RE, Zahurak ML, del Carmen MG, et al. Ovarian cancer surgery in Maryland: volume-based access to care. Gynecol Oncol 2004; 93:353.
- PATIENT SELECTION
- Indications for IP chemotherapy
- TECHNICAL ISSUES
- Timing of placement
- IP catheter and port
- CHEMOTHERAPY ADMINISTRATION
- Intravenous hydration
- - Nephrotoxicity
- - Neurotoxicity
- - Abdominal pain
- - Hypersensitivity reaction
- - Inability to access port or infuse the drug
- - Leakage of infusate
- - Gastrointestinal complications
- Diagnostic evaluation
- Bowel obstruction
- Gastrointestinal necrosis or perforation
- CATHETER REMOVAL
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS