Can the addition of oxiplatin to hyperthermic intraperitoneal chemotherapy improve the risk of colorectal peritoneal metastasis?

This study examined the appropriate dosage of oxaliplatin for use in hyperthermic intraperitoneal chemotherapy in colorectal cancer patients at risk for peritoneal metastasis.

Colorectal cancer that has spread to the peritoneum, the lining of the abdomen, generally has a poor prognosis, due to the difficulty of reaching this area with chemotherapy. A new procedure, hyperthermic intraperitoneal chemotherapy may be useful, as chemotherapy agents are circulated directly throughout the abdominal cavity.

Standard chemotherapy regimens are still being developed for this procedure. The chemotherapy agents used most often are mitomycin C (sticks the cell’s DNA together so the cancer cannot divide and grow) and 5-fluorouracil (interferes with the cancer cell’s production of DNA). Oxaliplatin (Eloxatin) is another chemotherapy agent often used in advanced colorectal cancer that is believed to inhibit DNA synthesis in cancer cells.

This study reports results from a Phase 1 clinical trial to determine the appropriate dosages and efficacy of the addition of oxaliplatin to the mitomycin C and 5-fluorouracil combination used in hyperthermic intraperitoneal chemotherapy in colorectal cancer patients at risk of peritoneal metastasis.

This clinical trial included 9 patients who underwent hyperthermic intraperitoneal chemotherapy following surgery to remove the primary colorectal tumor. Three patients received a 90 mg/m² dose of oxaliplatin, three received 110 mg/m², and three received 130 mg/m². All patients also received mitomycin C and 5-fluorouracil. Toxicities were measured for the first 30 days, after which patients were monitored every 3 months.

33% of patients (1 who received 90 mg/m² oxaliplatin, 2 who received 110 mg/m² oxaliplatin) saw increased bilirubin levels following treatment. Therefore 130 mg/m²was considered the maximal tolerated dose of oxiplatin. High levels of bilirubin are indicative of liver problems. However, no patient experienced serious or fatal toxicities. 

None of the patients experienced a recurrence of their original tumor or peritoneal metastasis in the two years of follow-up. 33% died due to distant metastases.

This study concluded that hyperthermic intraperitoneal chemotherapy including mitomycin C, 5-fluorouracil, and oxaliplatin may be feasible, safe and potentially protective in colorectal cancer. 

This Phase 1 clinical trial included a very small number of patients. Further controlled trials including larger numbers of patients should be undertaken to confirm this dosing regimen.