title: Toxicity associated with combination chemotherapy for osteosarcoma: a report of the cooperative osteosarcoma study (COSS 80).
abstract: The treatment-associated toxicity in 189 patients entered in the COSS-80 Study was analyzed. The sequential use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and cis-platinum may be additive or synergistic in causing renal toxicity. However, evaluation of the 48-h serum methotrexate level and the incidence of elevated serum creatinine levels throughout treatment failed to indicate prolonged methotrexate elimination or severe kidney damage from this regimen where an interval of 3 weeks between cis-platinum administration and the next course of HDMTX was mandatory. The treatment-related mortality was 3.2% (6 out of 189 patients). Three patients died of septicemia during chemotherapy-induced bone-marrow depression following treatment with adriamycin or the combination of bleomycin, cyclophosphamide, and dactinomycin (BCD). Three deaths occurred following the use of high-dose methotrexate with citrovorum factor rescue. Two of these deaths were associated with delayed excretion of methotrexate. The toxicity is within the range reported in the literature.
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001835:Body Weight; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008727:Methotrexate / Q000009:adverse effects; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D002955:Leucovorin; D008727:Methotrexate