Toxicity associated with combination chemotherapy for osteosarcoma: a report of the cooperative osteosarcoma study (COSS 80)

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 metho...

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Bibliographic Details
Published in:Journal of cancer research and clinical oncology 1983, Vol.106 (S1), p.14-18
Main Authors: JURGENS, H, BERON, G, WINKLER, K
Format: Article
Language:English
Subjects:
Acute Kidney Injury - chemically induced
Adolescent
Adult
Antineoplastic agents
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - adverse effects
Biological and medical sciences
Body Weight
Bone Neoplasms - drug therapy
Bone Neoplasms - mortality
Chemotherapy
Child
Child, Preschool
Cisplatin - administration & dosage
Cisplatin - adverse effects
Clinical Trials as Topic
Drug Therapy, Combination
Female
Humans
Leucovorin - administration & dosage
Leukopenia - chemically induced
Male
Medical sciences
Methotrexate - adverse effects
Osteosarcoma - drug therapy
Osteosarcoma - mortality
Pharmacology. Drug treatments
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Summary: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.
ISSN:0171-5216
1432-1335
DOI:10.1007/BF00625045