Hyperthermic intraperitoneal chemoperfusion is efficacious when used as part of multimodality therapy for low-volume peritoneal metastases of gastric cancer, suggests a prospective single-arm phase II trial.¹

Among the 19 patients enrolled, all of whom had stage IV disease with ­either carcinomatosis or positive peritoneal cytology, 37% achieved resolution of that extragastric disease when given laparoscopic hyperthermic intraperitoneal chemoperfusion in addition to conventional therapies, according to results reported at the Society of Surgical Oncology’s Annual Cancer Symposium. Complications were seen in 11% of procedures.

The patients had a median overall survival of more than 20 months from their first procedure and more than 30 months from the time of their metastatic disease diagnosis.

This [hyperthermic intraperitoneal chemoperfusion] approach appears safe, with an encouraging number of patients demonstrating no evidence of peritoneal disease after multimodality treatment that included laparoscopic hyperthermic intraperitoneal chemoperfusion.

— Brian Badgwell, MD, MS

Tweet this quote

“Patients with peritoneal metastases, even limited peritoneal metastases, have reported survival rates of 6 to 15 months,” noted first author Brian Badgwell, MD, MS, Associate Professor of Surgery at the University of Texas MD Anderson Cancer Center, Houston. “And as there are limited data to support the use of hyperthermic intraperitoneal chemoperfusion in patients with gastric cancer, current guidelines recommend systemic chemotherapy only or best supportive care for patients with stage IV disease.”

“This [hyperthermic intraperitoneal chemoperfusion] approach appears safe, with an encouraging number of patients demonstrating no evidence of peritoneal disease after multimodality treatment that included laparoscopic hyperthermic intraperitoneal chemoperfusion,” he summarized. “Comparative studies will be required to clarify what benefit, if any, laparoscopic hyperthermic intraperitoneal chemoperfusion adds to the overall survival outcomes.”

Study Details

Trial enrollment was limited to patients who had relatively low-volume or radiologically occult disease, because cytoreduction was not a part of the protocol, according to Dr. Badgwell. The investigators did specifically not calculate peritoneal carcinomatosis index (PCI), but just 6 of the 19 enrolled patients had positive cytology only.

All patients first received systemic chemotherapy as selected by their medical oncologist. They then underwent up to five 1-hour laparoscopic hyperthermic intraperitoneal chemoperfusion procedures using mitomycin C and cisplatin (plus thiosulfate for renal protection). Diagnostic laparoscopy was performed before each procedure, with collection of biopsies and peritoneal washings.

Patients who achieved resolution of their peritoneal disease, defined as negative cytology with no carcinomatosis and no metastasis evident on imaging, were offered gastrectomy.

On average, patients received eight cycles of systemic chemotherapy, Dr. Badgwell reported.

Of the 19 patients, 10 (53%) received a single hyperthermic intraperitoneal chemoperfusion procedure. Fourteen patients (74%) received chemoradiotherapy, in some cases between the procedures as allowed by the trial protocol.

Key Findings

Seven of the trial patients (37%) achieved resolution of their peritoneal disease, and five (26%) opted to undergo gastrectomy. Among the operated patients, four did well postoperatively (despite wound infections in two), whereas one had a complicated postoperative course requiring a lengthy hospital stay, according to Dr. Badgwell.

“We performed the resection at the very end and did not combine it with hyperthermic intraperitoneal chemoperfusion; it was just the gastrectomy alone. We wanted to do this in a safe fashion, and we were a little worried about outcomes combining gastrectomy and hyperthermic intraperitoneal chemoperfusion,” he noted. However, the investigators have recently activated a newer version of the trial in which some patients will have both procedures at the same time.

Median overall survival from the first hyperthermic intraperitoneal chemoperfusion treatment was 20.3 months for the entire trial cohort. The 1- and 2-year rates were 73% and 31%, respectively. And with a median follow-up of 18.9 months from the diagnosis of metastatic disease, median overall survival from that event—the trial’s primary endpoint—was 30.2 months. The 1-, 2-, and 3-year rates here were 95%, 68%, and 44%, respectively.

Of the 38 total hyperthermic intraperitoneal chemoperfusion procedures performed, 4 (11%) were associated with complications: intraoperative arrhythmia, elevation of creatinine, deep venous thrombosis, and pneumothorax. However, there were no deaths related to the procedure. The median hospital length of stay for a hyperthermic intraperitoneal chemoperfusion procedure was 3 days.

Insurance Approval

When asked by a session attendee about the difficulty of getting insurance approval for hyperthermic intraperitoneal chemoperfusion procedures, Dr. Badgwell acknowledged that insurance restricted coverage to a single procedure for one patient and that several others were unable to enroll because insurance would not cover it at all.

The major criticism of the study is the lack of a comparison group not given hyperthermic intraperitoneal chemoperfusion, acknowledged Dr. Badgwell. “But I was able to identify patients who, for insurance purposes or other reasons, did not go on the trial, and we will be writing that up and comparing them with the trial patients,” he noted. ■

Disclosure: Dr. Badgwell reported no potential conflicts of interest.

Reference

1. Badgwell B, Blum M, Das P, et al: A phase II study of laparoscopic hyperthermic intraperitoneal chemoperfusion (HIPEC) for gastric carcinomatosis or positive cytology. 2017 Society of Surgical Oncology Annual Cancer Symposium. Abstract 1. Presented March 17, 2017.