Glucocorticoid use in acute lymphoblastic leukaemia.
Glucocorticoids (prednisone and dexamethasone) play an essential part in the treatment of acute lymphoblastic leukaemia (ALL), but their optimum doses and bioequivalence have not been established. Results of preclinical studies have shown that dexamethasone has a longer half-life and better CNS penetration than does prednisone. In prospective randomised trials, dexamethasone improved control of CNS leukaemia. At a prednisone-to-dexamethasone dose ratio of less than seven, dexamethasone (6-18 mg/m(2) per day) resulted in a better event-free survival than did prednisone (40-120 mg/m(2) per day), and high-dose dexamethasone (10-18 mg/m(2) per day) improved the outcome of T-cell ALL and high-risk ALL. However, dexamethasone caused more adverse effects, including infection, bone fracture, osteonecrosis, mood and behaviour problems, and myopathy. At a dose ratio greater than seven, the two drugs showed no difference in efficacy. Therefore, the efficacy of prednisone and dexamethasone is dose dependent and needs to be carefully assessed against the toxic effects. Moreover, although dexamethasone generally showed increased activity in ALL cells in vitro, the dose ratio of the two drugs that exerted equivalent cytotoxic effects differed substantially in samples from individuals. The selection of the type and dose of glucocorticoid should be based on the risk of relapse, treatment phase, and the chemotherapeutic drugs used concomitantly.
Inaba
Hiroto
H
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-3678, USA. hiroto.inaba@stjude.org
Pui
Ching-Hon
CH
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D005938:Glucocorticoids