Researchers study new drug and indications for heated chemotherapy treatment

Mar 17 2008

Studies have shown that surgery combined with Intraperitoneal Hyperthermic Chemotherapy (IPHC) can improve survival rates for select patients with peritoneal carcinoma (cancer of the lining of the abdominal cavity) that has spread from colorectal or appendix cancer.

Researchers from Wake Forest University School of Medicine will present findings from two studies on the use of IPHC in treating peritoneal cancer that has spread from these two primary cancer sites at the annual meeting of the Society of Surgical Oncology in Chicago, March 13-16.

John H. Stewart, IV, M.D., assistant professor of surgery, section of surgical oncology, reports March 13 on the results of a study evaluating toxicity when combining surgery and IPHC using oxaliplatin as the chemotherapy agent in patients with peritoneal cancer which originated as colorectal or appendix cancer.

“A large body of literature suggests that oxaliplatin is superior to other chemotherapy agents in killing colorectal cancer cells,” said Stewart. “Further, we have previously demonstrated that the cancer-killing effects of oxaliplatin are increased when the agent is heated during perfusion.”

The purpose of the phase I study was to establish the maximum tolerated dose of oxaliplatin used in IPHC treating colorectal and appendix cancers that have spread to the peritoneum.

Fifteen patients were enrolled in the study at two dose levels, 200 mg/m² and 250 mg/m². At the maximum tolerated dose of 200 mg/m², only two significant toxicities were encountered. More severe toxicities were observed in patients receiving 250 mg/m².

Researchers concluded that IPHC with 200 mg/m² of oxaliplatin is well tolerated and is the maximally tolerated dose for a two-hour chemoperfusion.

“Based on the data from this phase I study, we propose to conduct a larger trial with oxaliplatin dose to study its efficacy in improving outcomes in patients with peritoneal carcinoma,” said Stewart.

On March 14, Perry Shen, M.D. associate professor, section of surgical oncology, will report findings on the use of IPHC in patients with peritoneal cancer and hepatic metastases (HM), or liver cancer that has metastasized from colorectal cancer. The use of IPHC in patients with this presentation is controversial.

“This was a retrospective study of 144 patients undergoing surgery to remove as much of the cancer as possible and IPHC between 1991 and 2007,” said Shen. There were 17 patients with HM. Clinical and pathological information was obtained from a prospectively collected database and electronic medical record.

Median overall survival for patients with and without HM was 22.7 months and 15.8 months respectively, which was not a significant difference. Two- and four-year survival rates for the HM patients were 34.0 percent and 11.3 percent. Further analysis demonstrated the presence of malignant fluid in the abdominal cavity to be a significant predictor of decreased survival in patients with HM.

“We concluded that patients with peritoneal carcinoma and hepatic metastases undergoing cytoreductive surgery and IPHC for colorectal cancer had no significant difference in overall survival compared to those without HM,” said Shen. “In select patients with peritoneal carcinoma and hepatic metastases, cytoreductive surgery and IPHC may have some benefit.” Malignant ascites, an accumulation of fluid in the peritoneal cavity, predicted a poor outcome.