Isolated lower extremity chemotherapeutic infusion for treatment of osteosarcoma: Experimental study and preliminary clinical report

PURPOSE: To increase the dose of drug delivered to a tumor while maintainin g tolerable systemic side effects, an interventional technique of isolated lower extremity infusion was investigated. MATERIALS AND METHODS: Experiments were performed in eight dogs. Four dogs were treated by a combination of intraarterial (IA) femoral cisplatin infus ion at a dose of 2.0 mg/kg with drug removal from the ipsilateral extremity venous blood by a dialyzer. The other four dogs comprised the control grou p. In these animals, left femoral arterial IA cisplatin infusion was perfor med without dialysis. Leukocyte and platelet counts, blood urea nitrogen (B UN) levels, and serum creatinine levels were recorded before and after the treatment. Subsequently, two human patients with inoperable osteosarcoma we re treated with the isolated infusion. RESULTS: In the experiments, 85%-90% of the free platinum that entered the dialyzer was removed. The peak systemic plasma cisplatin concentrations in animals undergoing dialysis were reduced by 81.25% compared to those in ani mals undergoing femoral IA infusion without hemodialysis. There were no sig nificant changes in the hematologic profiles or BUN and serum creatinine le vels in the experimental animals. However, in the control group, all dogs d eveloped myelosuppression and severe renal toxicity after IA infusion of th e same dose of cisplatin. Clinically, immediate relief of symptoms related to the primary tumor was achieved in both human patients after the combinat ion of isolated IA infusion and embolotherapy. CONCLUSION: Single-pass hemodialysis removed a significant amount of cispla tin after regional IA infusion, reduced systemic toxicity, and permitted su rvival of the experimental animals. In two patients with osteosarcoma, perc utaneous isolated lower extremity chemotherapeutic infusion therapy and emb olotherapy were performed safely with partial responses.