New principles, better practices, and clearer perceptions in intraperitoneal chemotherapy: clinical experience using icodextrin 20 as a carrier solution.
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.
Dobbie
J W
JW
Lister Research Laboratories, University Department of Surgery, Edinburgh Royal Infirmary, Scotland.
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D015314:Dialysis Solutions; D004337:Drug Carriers; D005472:Fluorouracil / Q000008:administration & dosage; D005936:Glucans / Q000008:administration & dosage*; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D000077607:Icodextrin; D007263:Infusions, Parenteral; D010534:Peritoneal Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D015314:Dialysis Solutions; D004337:Drug Carriers; D005936:Glucans; D000077607:Icodextrin; D005947:Glucose; D005472:Fluorouracil