three non-metastatic osteosarcoma patients were treated with high-dose methotrexate, adriamycin, and cisplatin from October 1987 to May 1993. Median age was 18. The ratio of male to female was 16: 7. The patients received methotrexate 8g/§³ IV, day 1 and 8 with leucovorin rescue, adriamycin 25mg/§³ IV day 16~18, and cisplatin 75mg/§³ IV day 16, After two cycles of neoadjuvant chemotherapy, operation was done and then six cycles of adjuvant chemotherapy were given with the same regimen. One patient developed lung metastasis after two cycles of neoadjuvant chemotherapy, and the other patient died from sepsis associated with chemotherapy-induced neutropenia before operation. Therefore, 21 patients underwent operation. Among them, l9 patients underwent limb salvage operation. Of the five patients who relapsed, two patients had lung metastasis and another two patients had local recurrence, and one patient had both lung and brain metastasis. One year, three year, and five year disease-free survival rate were 84%, 68%, and 68%. One year, three year, and five year survival rate were 91%, 64%, and 53%, respectively. The site of the primary lesion was the only significant prognosis factor. Patients with the lesion of distal femur had poor prognosis.Histologic responses were assessed in 17 patients. Observed histologic responses were grade I necrosis in 35%, grade II necrosis in 65%. There was no grade III or IV necrosis. The disease-free survival rates and overall survival rates were not significantly different between grade I necrosis group and grade II necrosis group. Toxicities grade III or IV were as follows: leukopenia 32%, thrombocytopenia 9%, hepatotoxicity 14%, and infection 6% with one chemotherapy-related death. The pharmacokinetics of high-dose methotrexate with leucovorin rescue were studied in l0 patients. The highest concentration was achieved at the end of infusion(6 hour). The decay of the plasma concentration of methotrexate after completion of the infusion followed a two-compartment model with a T(1/2)￥a of 3.4¡¾1.9 hours and T(1/2)￥a of 8.0¡¾2.6 hours. The clearance was 55¡¾13ml/min/§³ and the volume of distribution was 8.2¡¾3.0 L/§³. In conclusion, neoadjuvant chemotherapy with high-dose methotrexate, adriamycin, and cisplatin is effective for treatment of the patients of osteosarcoma with preserving the limb function.
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