Intraperitoneal chemotherapy for colorectal cancer

Abstract

The peritoneal surface remains an important failure site for patients with colorectal cancer. Peritoneal metastases of colorectal cancer are at present considered equal to distant metastatic disease. Consequently, peritoneal carcinomatosis is treated with systemic chemotherapy and surgery only to palliate complications such as obstruction. Despite the development of new chemotherapeutic agents and combinations, the results remain disappointing with a limited impact on survival. Colorectal carcinoma cells are relatively resistant to chemotherapy. Intraperitoneal chemotherapy seems to be an attractive approach in the treatment of high-risk colorectal cancer and peritoneal carcinomatosis from colorectal origin providing high local drug concentration with limited systemic side effects. Adjuvant early postoperative intraperitoneal chemotherapy is worthwhile for consideration as treatment option after resection of high-risk colorectal cancer. In the treatment of peritoneal carcinomatosis postoperative intraperitoneal chemotherapy leads to inadequate exposure of the peritoneal surface. Only an intraoperative intraperitoneal chemotherapy performed with direct cytotoxic drugs such as MMC and cisplatin overcome this problem. The limited drug penetration in tissue implies the need for extensive cytoreductive surgery. The results of phase II studies suggest that an increased median survival can be achieved with this approach. The natural history of this disease and the heterogeneity of the patients are such that only a randomized trial design will adequately answer the question whether regional treatment of patients with peritoneal dissemination of colorectal cancer actually prolongs survival. The results of such a study are to be expected in approximately 2 years time.

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

“…However, these favourable pharmacokinetic parameters may not correlate with the drug amount in peritoneal tumour nodules. It is more important to achieve also adequate tumour tissue penetration and concentration of the drug rather than high drug concentrations in the peritoneal fluid only [9].…”

Guidelines on the Use of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Surface Malignancy Arising from Colorectal or Appendiceal Neoplasms

“…Leucovorin (20 mg/ m 2 ) is given before the 5-fluorouracil, intravenously over 10 minutes. When mitomycin C is used 14,72 , the U.S. guidelines suggest 40 mg as a fixed dose to be delivered in 2 syringes 73,74 (loc b). Taking local habits, equipment, and funding into consideration, the ranges accepted in Canada are listed in Table vi.…”

The use of morphometric and fractal parameters to assess the effects of 5-fluorouracil, interferon and dexamethasone treatment on colonic anastomosis healing: an experimental study in rats

“…Therefore, early or immediate implementation of adjuvant chemotherapy seems to be beneficial in terms of residual disease, liver metastases and recurrence prevention, and has been demonstrated to improve disease outcomes [13,14]. The literature describing the effects of chemotherapeutics on the healing process is not wholly consistent, but several studies have reported the deleterious influence of 5-fluorouracil on the integrity of intestinal anastomosis.…”