Hyperthermic intraperitoneal chemotherapy (HIPEC) is emerging as a viable treatment option for patients with advanced epithelial ovarian cancer. Investigators have published a guide of recommendations to help clinicians implement a HIPEC program for their institution.

In recent studies, hyperthermic intraperitoneal chemotherapy (HIPEC) has been evaluated for use at the time of cytoreductive surgery in patients with both primary and recurrent epithelial ovarian cancer. In a 2018 New England Journal of Medicine (NEJM) study, researchers assessed patients with advanced stage ovarian cancer who were randomized to receive either interval debulking or interval debulking plus HIPEC. “In this study, patients receiving interval debulking and HIPEC experienced an improvement in overall survival of 1 year,” explains Anthony B. Costales, MD. “Since improvement in overall survival has been a void in ovarian cancer, this study represents a significant landmark.”

Since the 2018 NEJM study was published, there has been an uptick in the implementation of HIPEC for epithelial ovarian cancer throughout the United States, according to Dr. Costales. “However, many clinicians and institutions attempting to implement this approach may be doing so for the first time,” he says. With this in mind, Dr. Costales and colleagues published a review in Gynecologic Oncology that provided guidance and recommendations based on their extensive experience with HIPEC at the Cleveland Clinic. “Our review article is important because research shows that implementation of HIPEC for epithelial ovarian cancer in the US is increasing dramatically,” Dr. Costales says. “The Society of Gynecologic Oncology (SGO) surveys healthcare providers every 5 years to analyze trends in treatment. HIPEC was not mentioned 5 years ago in the SGO survey, but the most recent survey found that approximately 45% of clinicians are now offering HIPEC.”

Key Highlights According to the review article, establishing a HIPEC program requires a committed effort. “Given our experience with the procedure, we highlighted many aspects to consider when implementing this program, specifically personnel and training, patient selection, safety, and specific chemotherapy considerations,” says Dr. Costales. The study team offered evidence-based strategies for preoperative care and preparation, team and equipment requirements, and HIPEC protocols. They also provided insights on anesthesia and surgical considerations as well as postoperative considerations, specifically ICU admissions.

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The review noted that establishing a HIPEC program requires building a multidisciplinary team and educating each member on several important aspects of the procedure. Chemotherapy-certified personal protective equipment and a HIPEC pump, which is connected to inflow and outflow catheters placed within the peritoneal cavity, are required equipment. During HIPEC, 3-6 L of a hyperthermic perfusate—composed of an isotonic crystalloid vehicle and the chemotherapy of choice—should be infused through the peritoneal cavity with a goal temperature of 41-43°C.

Prior to infusing HIPEC, surgical teams are recommended to communicate with anesthesia and pharmacy members. Patients receiving HIPEC with cisplatin, furosemide and mannitol should be administered 1 hour before chemotherapy to ensure adequate diuresis. Sodium thiosulfate may be considered to protect the kidneys. A multiagent premedication protocol before HIPEC infusion should be considered to reduce hypersensitivity reactions, renal toxicity, and postoperative nausea.

Optimizing Implementation

“The recommendations from our review are generalizable to institutions nationwide and internationally,” says Dr. Costales. “For women with epithelial ovarian cancer, HIPEC is best served at large academic medical centers, because these patients may require a brief ICU stay following the procedure. Additionally, close patient monitoring is paramount, especially for electrolyte levels and fluid management.” Continuous patient monitoring and proactive management of abnormalities that arise during HIPEC is imperative to decrease patient morbidity and mortality.

Dr. Costales cautions that more research is needed for many aspects of HIPEC. “An ongoing clinical trial from the Netherlands is assessing HIPEC in the upfront setting,” he says, “and we eagerly anticipate data from this study. We also need to establish if there is a role for consolidation HIPEC and in secondary or greater debulking procedures. In addition, questions remain on how PARP inhibitors change the landscape of HIPEC for treating ovarian cancer. We look forward to having these unanswered questions addressed in future research.”