High dose melphalan in children with advanced malignant disease: a pharmacokinetic study

Nine children with poor-prognosis malignancies--seven with advanced neuroblastoma and two with metastatic Ewing's sarcoma--were given high doses of melphalan (HDM), 150 mg/m2 (3 patients) and 180 mg/m2 (6 patients), as a 'late intensification' agent combined with noncryopreserved auto...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 1985-01, Vol.15 (3), p.263-267
Main Authors: NINANE, J, BAURAIN, R, DE SELYS, A, TROUET, A, CORNU, G
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Chemotherapy
Child
Child, Preschool
Dose-Response Relationship, Drug
Half-Life
Humans
Infant
Kinetics
Male
Medical sciences
Melphalan - administration & dosage
Melphalan - metabolism
Melphalan - therapeutic use
Neoplasm Metastasis
Neuroblastoma - drug therapy
Neuroblastoma - metabolism
Pharmacology. Drug treatments
Sarcoma, Ewing - drug therapy
Sarcoma, Ewing - metabolism
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Summary:Nine children with poor-prognosis malignancies--seven with advanced neuroblastoma and two with metastatic Ewing's sarcoma--were given high doses of melphalan (HDM), 150 mg/m2 (3 patients) and 180 mg/m2 (6 patients), as a 'late intensification' agent combined with noncryopreserved autologous bone marrow transplants. Melphalan levels in the plasma decreased biphasically, with mean half-lives of 6.6 min and 3.0 h. At the time of marrow reinfusion (12-21 h after HDM) the melphalan plasma level was generally below 0.1 microgram/ml. The renal contribution to melphalan clearance was low, a mean of 5.8% of the injected dose being found in patients' urine over the 12 h following HDM administration. No significant difference was seen in pharmacokinetic parameters between patients undergoing and not undergoing forced diuresis.
ISSN:0344-5704
1432-0843
DOI:10.1007/BF00263898