Regional chemotherapy in an experimental model of Wilms' tumor in rats

Abstract

A s.c. experimental model of Wilms' tumor in rats was used to compare the effects of intratumoral treatment with vincristine plus actinomycin D to i.v. treatment with these chemotherapeutic drugs. The Wilms' tumor model is a fast-growing solid tumor that has been shown to be resistant to traditional clinical treatment procedures used for Wilms' tumor in man. Injection of the chemotherapeutic drugs directly into the tumor mass was found to be more effective than i.v. therapy in causing long-term remission of the tumor. Intratumoral therapy was also less toxic to the animals than i.v. therapy when measured by post-treatment survival rates and weight loss during the 1st week following treatment. However, intratumoral treatment caused an initial fibrosis of the tumor tissue, which resulted in a slower rate of absorption of the resultant fibrotic tumor mass than was seen in tumors treated i.v. Also, intratumoral injection resulted in necrosis of the overlying skin, which healed as the fibrotic tumor tissue was absorbed. Intratumoral treatment of a cervical tumor was found to cause the remission of a second major tumor mass located at some distance from the initial injection (i.e., in the lumbar region). No significant benefits were noted when dimethylsulfoxide (DMSO) was used in place of aqueous mannitol as a vehicle to deliver the chemotherapeutic agents. There was a significant correlation between the drug dose-to-tumor-size ratio (D/T ratio) and the effectiveness of the chemotherapy. When this ratio was high enough, a single treatment with a combination of vincristine and actinomycin D usually resulted in total remission of the experimental Wilms' tumor in response to either intratumoral or i.v. therapy.