Tumor Necrosis Rate to Peak Serum Level of MTX in the Preoperative Chemotherapy of Osteosarcoma

Son, Jung Whan; Kim, Jae Do; Jung, So Hak; Jaug, Jae Ho; Lee, Sang Mok; Kim, Chul; Cha, Jong Seo

Abstract

PURPOSE
High dose methotrexate (HDMTX) dramatically increases survival rate, which is related to the histologic response of tumornecrosis rate in the treatment of osteosarcoma. But, the study of tumor necrosis rate after preoperative chemotherapy with MTX has notbeen systemically evaluated. We analysed tumor necrosis rate versus related parameters such as the MTX serum peak level, age, sex, location, pathologic type under two chemotherapeutic protocols (modified T10 & T20). MATERIALS AND METHODS: From June 1995 to June 2001, 44 cases of Enneking stage IIB osteosarcoma patients (29 males, 15 females, mean age 18) were treated with two similar neoajuvant chemotherapeutic protocols involving intravenous injections of MTX, ifosphamide, adriamycin and the intra-arterial injection of cisplatin preoperatively. The histologic response to the chemotherapy was graded as complete(100% necrosis) or incomplete (less than 100%). RESULTS: Of 44 patients, 26 showed serum MTX concentrations greater than 1, 000 micromol/L. Complete response was seen in 9 patients with a peak serum MTX level of 1, 000 micromol/L or greater. Complete response was seen in 34.6% of patients with 1, 000 mol/L orgreater MTX serum peak level (p=0.031). Seven of 15 female patients showed complete response. Three of 29 male patients showed complete response. The complete response rate of females was significantly higher than that of males (p=0.019). Histological response was not significantly correlated with other variables. CONCLUSION: In this study, the rate of complete necrosis was significantly higher in patients with a preoperative peak serum MTX levelover 1, 000 micromol/L, especially in females, than in those with a serum MTX below this level. We suggest the preoperative dose of MTXserum peak level should be maintained at over 1, 000 micromol/L, and suggest that the preoperative MTX dose should be maintained at ahigh level in order to increase the tumor necrosis rate.