Standardization Is Key to Future of "Chemotherapy Bath"

Jesus Esquivel, MD

An increasing number of patients are presenting with peritoneal carcinomatosis, or widespread metastasis of the peritoneum, which can result from a variety of tumors, including digestive and gynecologic malignancies. ¹ The diagnosis is devastating, with treatment often limited to palliation of symptoms, but a combination of cytoreductive surgical resection (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)—sometimes referred to as “hot chemotherapy bath”—has the potential to provide some patients with long-term survival.

HIPEC is administered after CRS, with CRS attempting to remove all visible disease from the abdomen and HIPEC targeting any microscopic disease. A variety of chemotherapeutic agents can be used, depending on tumor type. The selected agent is heated before it is infused into the abdominal cavity. The heat is thought to help the chemotherapeutic agent kill any residual cancer cells, and flooding the abdomen with the agent is thought to expose cancer cells to higher concentrations of the selected drug than can be achieved with systemic chemotherapy.

After the drug has been deemed to sufficiently circulate through the abdomen (30-120 minutes), it is drained from the body, anastomoses are performed, and the abdomen is closed.² Patients may go on to receive systemic chemotherapy, particularly if they have more extensive or aggressive disease.

Although the procedure has been in use since the 1970s, HIPEC has been criticized for its lack of standardization, with the literature showing variations in the seven parameters used to characterize the procedure: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug used, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time.² Randomized controlled trials are still lacking to shed light on these issues; however, in 2009, the American Society of Peritoneal Surface Malignancies (ASPSM) was formed to improve the overall care of patients with peritoneal surface malignancies, and it set HIPEC standardization as its first goal.²

OncologyLive discussed this treatment in greater detail with Jesus Esquivel, MD, national director for HIPEC research, Department of Surgical Oncology, Cancer Treatment Centers of America, who has performed more than 500 such procedures and is also on ASPSM’s board of directors.

Q: Which patients with peritoneal carcinomatosis would be candidates for HIPEC, and would it always be paired with cytoreductive surgery?

The ideal patients would be those with limited amount of peritoneal carcinomatosis and with a diagnosis of a not very aggressive tumor, like mucionus tumors of the appendix, ovary, or colon. The results for more aggressive tumors, like pancreatic tumors, sarcomas, and gastric tumors, are not as good. For the most part, cytoreduction and HIPEC go together all the time. Sometimes HIPEC can be used without cytoreductive surgery as a palliative procedure for those patients with intractable ascites.

Q: One of the criticisms of HIPEC has been that there is no standardized approach— agents and methods can vary considerably. What approach do you apply? Is it the same for all patients or does it vary? If the latter, how do you decide?

In the past, there were tremendous variations on how HIPEC was delivered. Nowadays, most of us follow the recommendations published by the American Society of Peritoneal Surface Malignancies. The chemotherapy agent used will depend on the diagnosis of the patient. Mitomycin C is the most frequently used drug for gastrointestinal malignancies and a platinum agent would be the most commonly used for gynecological malignancies.

Q: Do you see HIPEC methods being standardized or improving in the future?

Absolutely. To be able to promote a therapy, there needs to be as much standardization as possible. There will always be some small variations that appear not to be clinically relevant, but even those will have to be standardized in the near future.

Q: Currently, it still seems to be a very taxing therapy, necessitating tube feedings for weeks after surgery. Has this been your experience?

As the selection criteria improve, I think the number of those cytoreductions that represent a heroic surgical effort will diminish. We need to work together with our medical oncologists to identify those patients who will benefit the most from a multidisciplinary therapy that includes systemic chemotherapy and cytoreductive surgery. The role of HIPEC will have to be demonstrated to make this procedure standard of care.

Q: What results have you seen with this treatment?

The outcome of patients undergoing cytoreductive surgery and HIPEC is directly related to the burden of disease and the histology of the tumor. For patients with low-grade tumors, like pseudomyxoma peritonei of the appendix, this procedure can be done with curative intent in many patients. For patients with colon cancer with peritoneal carcinomatosis, the outcomes continue to improve as systemic chemotherapy gets better. Most series now report median survivals of about 3 or more years. A decade ago, the median survival for patients treated with only systemic chemotherapy was less than 12 months.

Q: What have you learned from your experience?

I have learned that our biggest challenge is to identify the timing and sequence of all currently available therapies. At this time, those therapies include systemic chemotherapy, cytoreductive surgery, and HIPEC.

Q: What should healthcare providers know about HIPEC?

Multidisciplinary care is the hallmark of cancer care in 2015. Therefore, patients with peritoneal carcinomatosis should be evaluated also by a cytoreductive surgeon. At the present time, more than 90% of patients with colorectal cancer who are candidates for cytoreductive surgery and HIPEC are being treated only with systemic chemotherapy.

Q: What about patients? Are they prepared for how grueling this therapy can be?

I think that the days of “grueling” cytoreductive surgeries and HIPEC are diminishing quickly. We need to focus on patients who will derive a good long-term benefit and at the same time focus on diminishing the morbidity while preserving quality of life. Current outcome data demonstrate that this is possible.

References

1. Chia CS, Tan WJ, Wong JF, et al. Quality of life in patients with peritoneal surface malignancies after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Eur J Surg Oncol. 2014;40(8):909-916.
2. Esquivel J. Current status and future directions of hyperthermic intraperitoneal chemotherapy (HIPEC). http://www.interventionaloncology360. com/content/current-status-and-future-directions-hyperthermic- intraperitoneal-chemotherapy-hipec. Published June 23, 2104. Accessed July 14, 2015.