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New principles, better practices, and clearer perceptions in intraperitoneal chemotherapy: clinical experience using
1Lister Research Laboratories, University Department of Surgery, Edinburgh Royal Infirmary, Scotland.
Abstract:
The rationale for using intraperitoneal chemotherapy is based on three phenomena: certain types of tumor are confined to the abdominal cavity for many years; the ability to deliver the drug directly to the surface of tumor deposits; the pharmacological advantage of attaining high local concentrations of the drug within the cavity. Current techniques of intraperitoneal chemotherapy do not use a specially designed carrier solution, which greatly restricts flexibility and does not permit continuous ambulatory intraperitoneal chemotherapy necessary for optimal use of cell cycle-specific antitumor agents. Using icodextrin 20 as a carrier solution containing 50% of the dose of 5-fluorouracil in a 24-hour dwell, simultaneously with a 24-hour elastomeric infusor device containing 50% of the dose, we have succeeded in carrying out continuous ambulatory intraperitoneal chemotherapy, 5 days out of 7 for up to 12 weeks, exposing the peritoneal contents to drug concentrations a thousand-fold greater than attained in the serum in a Phase I clinical trial. These studies have for the first time demonstrated that it is possible to expose continuously for long periods intraperitoneal tumor deposits to sustained high levels of cell cycle-specific cytotoxic agents.
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