Chemotherapy and surgery in a murine osteosarcoma.

Surgical and chemotherapeutic effects on pulmonary metastatic disease were evaluated in the MGH-OGS murine osteosarcoma. The tumor responded to three sequential injections of doxorubicin with prolonged growth delay but cisplatin administration (although given in doses sufficient to cause weight loss and significant mortality) was not effective in controlling local disease progression. Using a protocol with three injections of doxorubicin (0.006 mg/g of body weight), it was observed that disease-free survival was enhanced when one of the three doses of doxorubicin was given at the time of surgery (perioperatively). By marginally resecting the primary tumor and permitting its regrowth, a model was developed with recurrent primary and metastatic disease present simultaneously. It was observed in this model that amputation or resection of the recurrent primary lesion resulted in pulmonary metastatic growth acceleration. Using this recurrent primary tumor model, doxorubicin's effect on pulmonary metastatic lesions was enhanced when the drug was given at the time of amputation.