The Study on Administration of High-Dose Methotrexate in Children with Osteosarcoma

Kim, Eun A; Im, Ho Joon; Lee, Hahng

Abstract

PURPOSE: We investigated serum levels of MTX and accompanying organic toxicities after administration of High-Dose Methotrexate (HDMTX).
METHODS
We reviewed a total of 42 courses of HDMTX administration in 6 patients who were diagnosed with osteosarcoma in Hanyang University Hospital from 1993 to 1997. The HDMTX was infused at the doses of 8~12 g/m2, and serum levels were assessed. Leucovorin administration was started 20 hours from the beginning of MTX infusion, and continued until the serum MTX level is below 1x10-7 mol/L and toxicities are not detectable.
RESULTS
Of 6 patients (4 males and 2 females), mean age at diagnosis was 11.6 years (8.5~15.6 years). Sites of origin included distal femur in 3, proximal tibia in 1, proximal fibula in 1 and proximal humerus in 1. Serum MTX levels were 1.87+/-0.69x10-4 mol/L at 12~23 hours, and 5.10+/-3.22x10-8 mol/L at 120 hrs after HDMTX infusion. Of 42 courses, hematologic toxicity greater than grade III was observed in 19(45.2%) resulting reduction of dose in 2 patients, and hepatic toxicity greater than grade III in 28(67%). The mean ALT levels was 680+/-563 U in 1st day, and mostly normalized in 10th day. Stomatitis was generally mild, except 1 patient with grade III toxicity. No renal or neurologic toxicity was observed, except 1 seizure episode due to SIADH.
CONCLUSION
HDMTX with leucovorin in osteosarcoma was well tolerated, and in majority of courses, serum MTX levels returned to non-toxic level after 120 hours and leucovorin will be desirable to administer during at least 5 days.