Normal hind limbs of Donryu rats were regionally perfused with Nitromin, and the effects were studied.
Tumor-inoculated hind limbs of similar rats were perfused with various concentrations of Nitromin, and comparable tumor-bearing rats were treated with consecutive intraperitoneal administrations of a large amount of Nitromin.
1. With one exception perfusion of normal limbs with Nitromin by the method described resulted in no more than transitory edema. Nitromin, perfused by this method, could be safely administered in a high dosage.
2. By bioassay it was determined that nineteen milligrams of Nitromin per kilogram of body weight remained in the host animal when twenty-five milligrams kilogram of body weight was perfused.
3. The survival rate of tumor-bearing animals in the group treated by regional perfusion was highest with twenty-five milligrams of Nitromin per kilogram of body weight (the perfused groups receiving twenty-five, ten, and five milligrams of Nitromin per kilogram of body weight, respectively). The survival rate was also better after perfusion with twenty-five milligrams per kilogram of body weight than with consecutive systemic administrations of a large amount of the same drug.
4. From the standpoint of fewer side effects due to the chemotherapeutic agent, regional perfusion was found to be better than consecutive systemic administrations.
5. By regional perfusion with anticancer agent, metastases as well as the primary tumor were cured. The possible significance of this mechanism is discussed.
From the Department of Orthopaedic Surgery, University of Tokyo, Hongo, Tokyo