Isolated lower extremity chemotherapeutic infusion for treatment of osteosarcoma: experimental study and preliminary clinical report.
OBJECTIVE
To increase the dose of drug delivered to a tumor while maintaining tolerable systemic side effects, an interventional technique of isolated lower extremity infusion was investigated.


METHODS
Experiments were performed in eight dogs. Four dogs were treated by a combination of intraarterial (IA) femoral cisplatin infusion 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 group. In these animals, left femoral arterial IA cisplatin infusion was performed without dialysis. Leukocyte and platelet counts, blood urea nitrogen (BUN) levels, and serum creatinine levels were recorded before and after the treatment. Subsequently, two human patients with inoperable osteosarcoma were 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 animals undergoing femoral IA infusion without hemodialysis. There were no significant changes in the hematologic profiles or BUN and serum creatinine levels in the experimental animals. However, in the control group, all dogs developed myelosuppression and severe renal toxicity after IA infusion of the same dose of cisplatin. Clinically, immediate relief of symptoms related to the primary tumor was achieved in both human patients after the combination of isolated IA infusion and embolotherapy.


CONCLUSIONS
Single-pass hemodialysis removed a significant amount of cisplatin after regional IA infusion, reduced systemic toxicity, and permitted survival of the experimental animals. In two patients with osteosarcoma, percutaneous isolated lower extremity chemotherapeutic infusion therapy and embolotherapy were performed safely with partial responses.
Wang
M Q
MQ
Division of Cardiovascular and Interventional Radiology, Stanford University Medical Center, Stanford, California, USA.
Dake
M D
MD
Wang
Z P
ZP
Cui
Z P
ZP
Gao
Y A
YA
D000293:Adolescent; D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001806:Blood Urea Nitrogen; D001859:Bone Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D003404:Creatinine / Q000097:blood; D003956:Dialysis; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007261:Infusions, Intra-Arterial; D007866:Leg / Q000098:blood supply / Q000473:pathology*; D007958:Leukocyte Count; D007970:Leukopenia / Q000209:etiology; D008297:Male; D023421:Models, Animal; D012516:Osteosarcoma / Q000188:drug therapy*; D010976:Platelet Count; D013921:Thrombocytopenia / Q000209:etiology
D000970:Antineoplastic Agents; D003404:Creatinine; D002945:Cisplatin