Intraperitoneal chemotherapy for treatment of ovarian cancer
- Joan L Walker, MD
Joan L Walker, MD
- Section of Gynecologic Oncology
- Department of Obstetrics and Gynecology
- University of Oklahoma Health Sciences Center
- Maurie Markman, MD
Maurie Markman, MD
- Clinical Professor of Medicine
- Drexel University College of Medicine
- Vice President for Patient Care Services
- National Director of Medical Oncology
- Cancer Treatment Centers of America
- Section Editor
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Deputy Editor
- Don S Dizon, MD, FACP
Don S Dizon, MD, FACP
- Deputy Editor — Oncology and Palliative Care
- Medical Gynecologic Oncology
- Massachusetts General Hospital
- Gillette Center for Women's Cancers
- Associate Professor, Medicine & Obstetrics and Gynecology
- Warren Alpert Medical School of Brown University
The most common route of ovarian cancer spread is within the peritoneal cavity. The benefit of administering chemotherapy directly into the peritoneal cavity is supported by preclinical and pharmacokinetic data. Compared with intravenous (IV) treatment, intraperitoneal (IP) administration permits a several-fold increase in drug concentration to be achieved within the abdominal cavity.
There is now a growing body of evidence showing a survival advantage for IP cisplatin as compared with IV administration of platinum along with intravenous taxane-based chemotherapy in women with optimally cytoreduced (to <1.0 cm) stage III epithelial ovarian cancer. The publication of results from the most recent of these trials, Gynecologic Oncology Group (GOG) trial 172 , led the US National Cancer Institute to issue a Clinical Alert in January of 2006, strongly encouraging the use of IP chemotherapy in this subset of patients . A reassessment of prognostic factors associated with survival from both GOG 172 and 114 demonstrated a median overall survival on the IP arm of 110 months for stage III patients completely resected to no residual disease, compared with 82.4 months when treated intravenously . GOG 172 IP arm was even better with a median survival of 128 months. Age and histology were associated with survival. Patients with resected positive lymph nodes benefited from IP chemotherapy. Patients with unevaluated retroperitoneal nodes had the worst survival, but also benefited from IP chemotherapy. The Society of Gynecologic Oncology has made the offering and delivery of IP chemotherapy a quality indicator for ovarian cancer care. Many oncologists are reluctant to deliver IP chemotherapy. However, while the use of IP chemotherapy is gaining acceptance, it is not universal, largely due to the greater toxicity associated with this approach. The data supporting IP chemotherapy as an alternative to IV chemotherapy and the controversy surrounding its use are presented elsewhere. (See "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tubal, and peritoneal cancer", section on 'Intraperitoneal chemotherapy'.)
The management of women receiving IP chemotherapy for ovarian cancer, including issues relating to placement of intraperitoneal catheters, will be reviewed here. Surgical therapy and initial chemotherapy for advanced ovarian cancer are discussed 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".)
Epithelial ovarian cancer is a disease of the ovarian surface epithelium. In the vast majority of patients, the disease 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. Subsequent studies demonstrated that IP administration of chemotherapy results in high peritoneal to plasma ratios for peak concentration, including for cisplatin, paclitaxel, carboplatin, and docetaxel . Of these agents, cisplatin has been the most extensively studied and clinical studies have confirmed its activity in the front-line treatment of ovarian cancer. (See "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tubal, and peritoneal cancer", section on 'Intraperitoneal chemotherapy'.)
IMPORTANCE OF INITIAL SURGICAL CYTOREDUCTION
Despite the regional advantage of IP chemotherapy, penetration into tumor tissue is limited to a few millimeters of tumor on the peritoneal surface layers and these approaches are best suited to patients with minimal residual disease after surgical cytoreduction. A significant obstacle to realizing the survival benefit from IP chemotherapy is the wide variation in the proportion of women who undergo complete cytoreductive surgery to no residual disease. As an example, in a meta-analysis of 6685 women treated in the platinum era, optimal surgical resection was only carried out in 42 percent of cases . Although rates of optimal cytoreduction are significantly higher when trained gynecologic oncologists perform the surgery (75 percent or higher), patterns of care studies suggest that only about 50 percent of patients being treated for ovarian cancer are treated by gynecologic oncologists [7,8]. (See "Cancer of the ovary, fallopian tube, and peritoneum: Staging and initial surgical management", section on 'Cytoreduction'.)
- Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006; 354:34.
- NCI Clinical Alert available online at www.nlm.nih.gov/databases/alerts/ovarian_ip_chemo.html (Accessed on April 27, 2011).
- Landrum LM, Java J, Mathews CA, et al. Prognostic factors for stage III epithelial ovarian cancer treated with intraperitoneal chemotherapy: a Gynecologic Oncology Group study. Gynecol Oncol 2013; 130:12.
- 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.
- 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.
- 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.
- 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.
- Black D, Levine DA, Nicoll L, et al. Low risk of complications associated with the fenestrated peritoneal catheter used for intraperitoneal chemotherapy in ovarian cancer. Gynecol Oncol 2008; 109:39.
- 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.
- 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.
- Whitney CW. Gynecologic Oncology Group Surgical Procedures Manual. July 2005.
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- 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.
- Information on IP chemotherapy from the Gynecologic Oncology Group (GOG) available online. www.gog.org/IPChemoEd/ipchemoed.html (Accessed on April 26, 2012).
- 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.
- Fujiwara K. Can carboplatin replace cisplatin for intraperitoneal use? Int J Gynecol Cancer 2008; 18 Suppl 1:29.
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- 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.
- IMPORTANCE OF INITIAL SURGICAL CYTOREDUCTION
- INDICATIONS AND CONTRAINDICATIONS
- IP CATHETER AND PORT
- - Summary
- SURGICAL PROCEDURE
- Placement during initial laparotomy
- Delayed insertion
- Procedure for chemotherapy administration
- Catheter removal
- Prevention and management of complications related to chemotherapy
- - Nephrotoxicity
- - Abdominal pain
- - Neurotoxicity
- Catheter-related complications
- - Inability to access port or infuse the drug
- - Leakage of infusate
- - Peritonitis, abscess, bowel injury
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS