Challenges of IP Chemotherapy for Ovarian Cancer

Ms. Hydzik's article on intraperitoneal chemotherapy (IPC) for the treatment of ovarian cancer provides the rationale for IPC, presents the supporting evidence, and describes nursing management of these patients through the Memorial Sloan-Kettering Cancer Center experience. I would first like to briefly address two practice issues mentioned in her article: the concept of warming the solutions for IPC and the flushing of the IP port-a-cath. Second, Ms. Hydzik identifies the need for education of patients and staff about IPC, and I would also like to expand on some general thoughts as to why IPC may be underutilized in the clinical setting of women with epithelial ovarian cancer.

Because there is no evidence-based research to provide guidance on flushing of the IP port-a-cath, flushing protocols are varied among institutions. Some institutions may terminally flush with heparinized normal saline and others may terminally flush with normal saline alone. The argument for normal saline alone may be that the catheter is not placed in a blood vessel. However, one could argue that blood cells may be released into the peritoneal fluid by virtue of chemical irritation of the peritoneum from chemotherapeutic agents. In addition, blood cells may be released into the peritoneal fluid as a result of breakdown of residual tumor. Until evidence-based research addresses this issue, my institution follows the flushing policy and procedure for the IV chest port-a-cath; we terminally flush with 5 mL of 500 units of heparinized saline.

As Ms. Hydzik notes, use of hyperthermia in IPC postsurgery is controversial. Those who advocate heating the IP solution believe there are added benefits, given that heat increases drug penetration into tissue, heat increases cytotoxicty of selected chemotherapeutic agents, and heat by itself has an antitumor effect. Also, as she points out, warming the solution may prevent chilling caused by large amounts of fluid, at room temperature, placed into the peritoneum.

If using heat, safety is established at 42 degrees Celsius up to a duration of 2 hours. Arguments against hyperthermic intraperitoneal chemotherapy (HIPEC) in the postsurgical setting include the difficulty in monitoring and maintaining temperature during IP therapy. Use of HIPEC at the time of surgery has documented favorable outcomes. Intraoperative HIPEC is well controlled, whether one is utilizing the open or closed method.

Since the announcement 3 years ago by the National Cancer Institute (NCI) recommending IPC in the ovarian cancer setting, it has been reported that IPC in ovarian cancer has been underutilized despite evidence of its benefits. As Ms. Hydzik describes, there is evidence that broad implementation of IPC into daily practice, for a select population of patients, will improve their survival. Historically, IPC has been performed in the clinical research setting. Clinical management of IPC requires coordination of care that includes scheduling of the IP port placement, multiple treatment visits, and intensive physician and nursing support for managing IP-related side effects and/or complications. Lack of experience and knowledge regarding physical, psychological, social, spiritual, and financial aspects of care associated with IPC make taking this treatment modality out of the clinical research setting a challenge.

Institutions need to have a foundation in place to support what is in many settings a new concept of drug delivery. In addition to Ms. Hydzik's recommendations regarding nursing and physician education, there is a need for these institutions to develop and implement interdisciplinary education, interdisciplinary standards that describe each team member's role in IPC, policies and procedures, and patient education. Comprehensive nursing guidelines and better symptom assessment tools are needed to diminish variability in practice and more effectively target symptom interventions.[1,2]

Ms. Hydzik provides a discussion of nursing diagnosis/problems with interventions in Table 4. Although oncology nurses are very familiar with IV chemotherapy administration and management of their side effects, the IV/IP regimen brings an increase in short-term side effects and complications specific to the procedure itself. Increased toxicity results from the added drug dose from combined IV/IP chemotherapy, and these side effects are prolonged because of the delayed absorption of IPC into the systemic circulation. For example, use of IP cisplatin at a dose of 100 mg/m² requires management of nausea and vomiting and prevention of renal toxicity, respectively, by administering antiemetics and fluid hydration over a longer period than with IV cisplatin alone.

Abdominal pain is the most common complaint during IP therapy and is caused mainly by large volumes of fluid being instilled into the peritoneum, as well as loculation of IP fluid. In addition to IP cisplatin, IP paclitaxel and other agents may be used.Depending on the IP chemotherapeutic agent given, what is the least amount of fluid that can be instilled yet cause adequate abdominal distention to ensure adequate distribution of the infusate? Abdominal pain can also be an indicator of bacterial or chemical peritonitis. Shortness of breath or dyspnea can be due to the intra-abdominal pressure of IP therapy, but also can result from hypersensitivity to the chemotherapeutic agent. In addition to side effects and complications, increased nursing support during therapy is needed for bedpan assistance, owing to the bed rest restriction to prevent needle dislodgement.

Looking at practice patterns from a surgical standpoint, the NCI recommendation and the strongest evidence supports IPC for women with stage III ovarian cancer who have undergone optimal cytoreductive surgery with residual disease < 1 cm. What percentage of women present for treatment postsurgery with residual disease < 1 cm? It is reported that 75% of women newly diagnosed with ovarian cancer have advanced disease. It is also documented that the majority of women diagnosed with ovarian cancer have their initial surgery performed by a general surgical or gynecologic oncologist. Evidence in the literature shows ovarian cancer patients whose initial surgery is performed by a gynecologic oncologist or other physician with special expertise and training in ovarian cancer cytoreductive surgery are more likely to have optimal tumor reduction. There is geographic variation regarding access to gynecologic oncologists for initial management of ovarian cancer. Among gynecologic oncologists, expertise in cytoreductive surgery is varied, depending upon institutional setting. This adds to the underutilization of IPC.

A recent mail survey conducted among members of the Society of Gynecologists and the American Society of Clinical Oncology (ASCO) to evaluate practice patterns of IPC in women with ovarian cancer revealed that a standard for IPC administration to women with ovarian cancer is lacking.[3] Among the 213 respondents, 91% indicated they currently offer or plan to offer IPC in the near future. The survey found 58% of respondents use the outpatient setting but found the IP chemotherapy was administered at a lower dose than that used in clinical trials, and 13% of respondents only use IP chemotherapy when the residual disease is greater than 1 cm. These findings address the inherent need for standardization of care delivery for women with ovarian cancer.

In conclusion, I support Ms. Hydzik's recommendation that, to optimize outcomes, women with ovarian cancer who are candidates for IP chemotherapy should be referred to institutions experienced with this procedure. It will be incumbent upon these institutions to guide nursing practice in the care of these patients. The oncology nurse is in a position to work within a multidisciplinary group to establish institutional and nursing standards for the routine administration of IPC in the practice setting.

References:

References

1. Fung-Kee-Fung M, Provencher D, Rosen B, et al: Intraperitoneal chemotherapy for patients with advanced ovarian cancer: A review of the evidence and standards for the delivery of care.

Gynecol Oncol

105(3):747–756, 2007.
2. Marin K, Oleszewski K, Muehlbauer P: Intraperitoneal chemotherapy: Implications beyond ovarian cancer.

Clin J Oncol Nurs

11(6):881–889, 2007.
3. Naumann RW, Sukumvanich P, Edwards RP: Practice patterns of intraperitoneal chemotherapy in women with ovarian cancer.

Gynecol Oncol

114(1):37–41, 2009.