Principles of intraperitoneal chemotherapy
- dose - response relationship
Intraperitoneal application of drugs such as cytostatic agents will lead to high local drug concentrations in the abdominal cavity. Due to the existence of a dose - response - relationship for cytostatic agants such increase in local drug concentrations will lead to an increase in response rates.
- peritoneal plasma barrier
Large molecular weight compounds when instilled into the peritoneal cavity are sequestered at that site for long periods. The physiologic barrier to the release of intraperitoneal drugs is called the peritoneal space to plasma barrier. This means that the exposure of peritoneal surfaces to pharmacologically active molecules can be increased considerably by giving the drugs via the intraperitoneal as opposed to intravenous route.
Benefits of intraoperative chemotherapy
Intraoperative chemotherapy allows a uniform distribution of drugs to all surfaces of the abdomen and pelvis.
Nausea and vomiting are avoided because the patient is under general anesthesia
Limits of intraperitoneal chemotherapy
Intracavitary instillation allows very limited penetration of drug into tumor nodules. Only the outermost layer (~1 mm) of a cancer nodule is penetrated by the chemotherapy. This means that only minute tumor nodules can be definitively treated. Microscopic residual disease is the ideal target for intraperitoneal chemotherapy protocols.
A second cause for limited success with intraperitoneal chemotherapy is a non-uniform drug distribution. A majority of patients treated by drug instillation into the abdomen or pelvis had prior surgery, which invariably causes scarring between peritoneal surfaces. The adhesions create multiple barriers to the free access of fluid. Although the instillation of a large volume of fluid will partially overcome the problems created by adhesions, some surface areas will have no access to chemotherapy. Limited access from adhesions was impossible to predict and increased with repeated instillations of chemotherapy solutions.
Only an intraoperative use of intraperitoneal chemotherapy can overcome the problem of non-uniform distribution.