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Treatment of Ovarian Cancer With Intraperitoneal Chemotherapy

Treatment of Ovarian Cancer With Intraperitoneal Chemotherapy

ABSTRACT: In early 2006, the National Cancer Institute (NCI) issued a Clinical Announcement suggesting that intraperitoneal (IP) chemotherapy should become the standard of care for patients with newly diagnosed stage III optimally debulked epithelial ovarian cancer. IP chemotherapy, the administration of chemotherapy or biologic therapy via catheter into the peritoneal space, is new to many healthcare providers (physicians, nurses, and pharmacists). The goals of this article are to address the rationale for IP chemotherapy, present the data supporting its use, and describe the nursing management of patients undergoing this treatment. Education of patients and staff regarding IP therapy is essential for successful patient outcomes.

Ovarian cancer is the most deadly gynecologic malignancy. In the US alone, an estimated 21,500 new cases will be diagnosed in 2009, and an estimated 14,600 women will die from this disease.[1] Early-stage ovarian cancer is generally asymptomatic, so most patients with ovarian cancer present at an advanced stage of disease. The tumor stage is a significant prognostic variable, and patients with advanced disease have poorer outcomes.

TABLE 1
Three Randomized Clinical Trials of IP Therapy That Led to the National Cancer Institute's 2006 Announcement About Its Benefits

Several large clinical trials were conducted to identify the best treatment options for women with advanced ovarian cancer. Data generated by these studies led to the 2006 National Cancer Institute (NCI) Clinical Announcement recommending that intraperitoneal (IP) chemotherapy become the standard of care for patients with newly diagnosed stage III optimally de-bulked epithelial ovarian cancer.[2] Table 1 summarizes the three main clinical trials that demonstrated a significant improvement in survival among ovarian cancer patients treated with chemotherapy via the IP route, as opposed to the intravenous (IV)-only route.[3–5] The NCI reported that clinical trials showed the IP method to be safe and effective, and this report sparked a renewed interest in IP chemotherapy.

TABLE 2
IV/IP PACLItaxel IP CISplatin Regimen Used at Memorial Sloan-Kettering Cancer Center

In the past, healthcare providers were wary of IP chemotherapy for several reasons: IP chemotherapy required more resources and was more involved than IV chemotherapy. It required providers to master a new and complicated technique. Furthermore, there were concerns regarding IP chemotherapy study designs and outcomes. Healthcare providers needed to identify ideal candidates, that is, patients with limited, small-volume residual disease without adhesions. In addition, there were many reported toxicities with IP chemotherapy, including leukopenia and thrombocytopenia; gastrointestinal, renal, neurologic, and metabolic complications; fatigue; infection; and pain.[3–5] These toxicities may be expected with use of a higher IV cisplatin dose (100 mg/m2 vs 75 mg/m2) and addition of IP paclitaxel on day eight.[6] At Memorial Sloan-Kettering Cancer Center (MSKCC), we use a lower cisplatin dose (75 mg/m2) in an attempt to reduce these toxicities (see Table 2).

The Gynecologic Oncology Group (GOG) trial 172 by Armstrong et al.[3] showed prolonged progression-free interval and time to death for the IP group, suggesting a therapeutic advantage for IP therapy. It also evaluated the effect of IP chemotherapy on patients' Quality of Life (QOL). Patients receiving the higher dose of IP therapy experienced lower QOL initially vs those who received more conventional IV therapy. These differences disappeared over time. At 1 year, QOL and pain scores were similar between the two arms except for paresthesias, which were more likely to persist at moderate levels in patients on the IP/IV arm.[2] These findings suggest that the additional toxicity that may be seen with the IP route is transient and not a long-term issue for most patients.

The 2009 National Comprehensive Cancer Network (NCCN) Practice Guidelines for Stage II–IV ovarian cancer outline the treatment recommendations to be IP chemotherapy for patients who were optimally debulked (< 1 cm) or IV taxane/carboplatin for a total of 6–8 cycles.[7] Three years after the NCI announcement, it has been reported that IP chemotherapy has been underutilized as a treatment modality in the ovarian cancer patient, despite evidence of its benefits.[6] Several factors may account for this, including problems with study designs reported in the medical literature, toxicities, and technical complications with the procedure. Future clinical trials will study different agents and schedules to address survival outcomes and quality of life of women with ovarian cancer.

A challenge is to learn how to safely administer IP chemotherapy. At some institutions, the healthcare team may only see a few cases per year, making it difficult to learn this technique and establish standards of care. One suggestion is to inform patients about IP chemotherapy as a treatment option. If patients opt for this treatment, then they should be referred to institutions that offer IP therapy as a treatment modality.[7]

Staff Education

TABLE 3
Internet Resources on IP Chemotherapy

Successful implementation of IP as a treatment modality requires education and experience. Development of a procedure and standards of care is essential. At MSKCC, we found it helpful to develop an IP manual containing copies of the procedure for administration of IP chemotherapy, a skills checklist for IP chemotherapy, and pertinent literature (NCI announcements, recent studies, articles, and resources related to IP chemotherapy) so that staff members can have information and references readily available to them. (Table 3 provides selected Internet resources.)

Defining Patient Selection

The NCI recommendation for treatment of ovarian cancer includes surgery followed by chemotherapy, and IP chemotherapy is the standard of care for patients with newly diagnosed stage III optimally debulked epithelial ovarian cancer.[2] The patient's tumor size is a factor in the success of IP therapy. Because IP chemotherapy penetrates only a few millimeters into the tumor, the women most likely to respond to it are those with the smallest possible volume of residual disease. The current standard is for the woman to have optimal cytoreduction with tumor nodules no greater than 1 cm in diameter prior to IP treatment. Another consideration is the presence and amount of adhesions, as extensive intra-abdominal adhesion limits the effectiveness of IP chemotherapy.[8]

Rationale for IP Therapy

Prior to treating patients, the nurse should understand the natural history of ovarian cancer and the rationale for IP chemotherapy, and be able to identify ideal candidates. IP chemotherapy is regional administration of drug into the peritoneal cavity. There has been interest for about 30 years in use of IP therapy. It was first introduced in 1955 by Weisberger et al.,[9] who used nitrogen mustard intraperitoneally to treat malignant ascites. Dedrick et al.[10] published the landmark theoretical modeling study, which used a mathematical model that shows the pharmacokinetic rationale for IP therapy. Certain agents were shown to have a greater concentration and longer half-life in the peritoneal space vs IV administration.[10] Cisplatin has been found to have a 10–20 fold greater exposure when administered intraperitoneally vs intravenously.[11] Paclitaxel has more than 1,000-fold greater exposure when administered by the IP route.[12]

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