SAFETY AND EFFICACY OF L-LEUCOVORIN RESCUE FOLLOWING HIGH-DOSE METHOTREXATE FOR OSTEOSARCOMA

High-dose methotrexate with leucovorin rescue (HDMTX-LCV) is an import ant component of regimens used in the treatment of osteosarcoma. As of this writing the commercially available form of leucovorin is a racem ic mixture of d- and l-diastereoisomers; the l-isomer is the active co mponent. This study describes the efficacy and safety of l-leucovorin in HDMTX-LCV regimens. Fifteen patients with osteosarcoma who were enr olled into or treated according to Pediatric Oncology Group protocols 8759 and 8651 received l-leucovorin (7.5 mg every 6 hours) in place of d,l-leucovorin following high-dose methotrexate. Safely data were col lected for 1 week after each course until any toxicities resolved. The mean number of l-leucovorin doses per course was 16.2 and the mean to tal dose per course was 126 mg. Adverse experiences were generally mil d or moderate and occurred in 54 (60%) of 90 courses of l-leucovorin t herapy. One l-leucovorin patient, who had inadequate methotrexate resc ue, developed severe typhlitis. There were no instances of severe, acu te methotrexate toxicity. Myelosuppression was seen but, in general, w as not severe. These results support the conclusion that l-leucovorin effectively rescues patients from the toxicity of high-dose methotrexa te. (C) 1995 Wiley-Liss, Inc.