Alkylating activity in serum, urine, and CSF following high-dose ifosfamide in children

Cancer Chemotherapy and Pharmacology
J NinaneG Cornu

Abstract

The pharmacokinetics of alkylating activity were studied in 17 children treated i.v. with ifosfamide (IF) at 3 g/m2 as a 1-h infusion for 2 consecutive days every 3 weeks, with mesna as a uroprotector. Two patients were treated for a newly diagnosed rhabdomyosarcoma according to the current SIOP (International Society of Pediatric Oncology) protocol. The other 15 patients were treated in a phase II study and presented with one of the following malignancies in relapse: neuroblastoma (7), osteosarcoma (3), soft tissue sarcoma (2), Wilms' tumor (1), non-Hodgkin's lymphoma (1), and acute lymphoblastic leukemia (1). Plasma alkylating activity levels determined by using 4(4'-nitro-benzyl)-pyridine showed considerable inter-individual and intercyclic variations and decreased biphasically, with mean alpha and beta half-lives of 60 min and 6-7 h, respectively. Probably as a result of liver mixed-function oxidase induction, on the 2nd day of treatment the terminal half-lives were shorter, the plasma exposures were lower, and the mean plasma clearances were higher. Renal excretion was almost complete after 24 h, accounting for a mean of 19% of the injected dose. The CSF alkylating activity levels, obtained in four children, were always lo...Continue Reading

Citations

Jan 1, 1991·Cancer Chemotherapy and Pharmacology·J BoosG Schellong
Jan 1, 1991·Journal of Cancer Research and Clinical Oncology·W P BradeC E Araujo
Jun 17, 2016·Expert Review of Neurotherapeutics·Antonin DréanAhmed Idbaih
Feb 1, 1991·Journal of Neuro-oncology·T E ElliottB W Scheithauer

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