Preoperative administration of high-dose methotrexate for osteosarcoma.

Nine patients, aged 9 to 27 years (median 16 years), with osteosarcoma were given high-dose methotrexate followed by folinic acid rescue before amputation. The dose of methotrexate was 12 g/m2 for children under 12 years of age and 8 g/m2 for those over 12 years. Amputation was done after two to five (median four) courses of the drug. Between 5% and 60% of tumour cells were nonviable on histologic examination. No renal or hematologic toxicity was encountered. Mild mucositis and abnormal liver chemistry were present, usually after the third dose of methotrexate. Patients who achieved higher serum methotrexate levels at 24 hours after administration also had greater tumour necrosis. Postoperatively, chemotherapy was changed to cis-platinum, doxorubicin, cyclophosphamide, actinomycin and bleomycin. Seven patients finished their medication 17 to 35 months after diagnosis. One patient died after refusing chemotherapy postoperatively and another is alive with pulmonary metastases. Preoperative chemotherapy is a novel approach to the treatment of osteosarcoma and further modification of the treatment protocol may improve results.