title: Comparison of the antileukemic activity in vitro of dexamethasone and prednisolone in childhood acute lymphoblastic leukemia.
abstract: It is generally assumed that prednisolone (PRD) and dexamethasone (DXM) have equal glucocorticoid activity of PRD is given at sevenfold higher doses. Results of clinical studies of childhood acute lymphoblastic leukemia (ALL) suggested that DXM is more potent relative to PRD than assumed. The purpose of this study was to determine the relative antileukemic activity of PRD phosphate and DXM phosphate in 133 untreated childhood ALL samples in vitro, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT) assay. There was a marked variation in antileukemic activity of both agents among the patient samples. The median LC50 (drug concentration lethal to 50% of the ALL cells) for PRD phosphate was 3.50 microM, for DXM phosphate 0.20 microM. The individually calculated ratios of the LC50 values for PRD and DXM phosphate showed a large range from 0.7 to >500, with a median of 16.2. This 16-fold difference could not be explained by differences between these glucocorticoids in stability, hydrolysis into unesterified drug, adhesion to the wall of the microculture plates, or protein binding. ALL cells were cross-resistant to PRD and DXM phosphate (correlation coefficient = 0.85, P<0.000001). We conclude that the in vitro antileukemic activity of DXM phosphate is median 16-fold higher than that of PRD phosphate, which contrasts to the generally assumed factor of 7. Based on the higher potency of DXM, and its more favorable pharmacokinetics as reported in the literature, DXM may be preferred to PRD as the glucocorticoid in the treatment of ALL.
authors.affiliation: Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Kaspers
authors.forename: A J
authors.initials: AJ
authors.lastname: Veerman
authors.forename: C
authors.initials: C
authors.lastname: Popp-Snijders
authors.forename: M
authors.initials: M
authors.lastname: Lomecky
authors.forename: C H
authors.initials: CH
authors.lastname: Van Zantwijk
authors.forename: L M
authors.initials: LM
authors.lastname: Swinkels
authors.forename: E R
authors.initials: ER
authors.lastname: Van Wering
authors.forename: R
authors.initials: R
authors.lastname: Pieters
mesh_terms: D000293:Adolescent; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002648:Child; D004396:Coloring Agents; D003907:Dexamethasone / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C009022:prednisolone phosphate; D003907:Dexamethasone; D011239:Prednisolone; C022616:thiazolyl blue