Comparison of 'sequential' versus 'standard' chemotherapy as re-induction treatment, with or without cyclosporine, in refractory/relapsed acute myeloid leukaemia (AML): results of the UK Medical Research Council AML-R trial

Liu Yin, J. A., Wheatley, K, Rees, John K. H. and Burnett, Alan Kenneth 2001. Comparison of 'sequential' versus 'standard' chemotherapy as re-induction treatment, with or without cyclosporine, in refractory/relapsed acute myeloid leukaemia (AML): results of the UK Medical Research Council AML-R trial. British Journal of Haematology 113 (3) , pp. 713-726. 10.1046/j.1365-2141.2001.02785.x

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Abstract

This aim of the acute myeloid leukaemia (AML)-R trial was to compare sequential (Seq) ADE (cytarabine, daunorubicin, etoposide) with standard (Std) ADE as remission re-induction treatment and to assess any benefit of cyclosporine (CSA) as a multidrug resistance modulator in refractory/relapsed AML patients. Seq ADE, based on the concept of Timed Sequential Therapy, comprised the same drugs as Std ADE but given at higher doses and in a different sequence. Between 1992 and 1997, 235 patients with relapsed (175) and refractory (60) AML were entered: 170 were randomized between Std versus Seq ADE and 213 between CSA versus no CSA. CSA was initially given at a dose of 5 mg/kg/d and increased to 10 mg/kg/d in the latter part of the trial. Overall, the complete remission (CR) rate was 43%, with Std ADE being significantly better than Seq ADE (54% versus 34%, P = 0.01). CR rates did not differ between the CSA and no CSA arms (41% versus 45%, P = 0.6). Overall, 3 year disease-free survival (DFS) of remitters was 16%, with a relapse risk of 70%. DFS was not significantly different between the chemotherapy or the CSA arms. Overall, 3 year survival was 8%. Survival with Std ADE was significantly better than with Seq ADE (12% versus 6%, P = 0.03). CSA did not affect overall survival, except in patients > or = 60 years, who fared worse on CSA (P = 0.0003). No difference in haematological toxicity between the chemotherapy or CSA arms was seen. Survival was better with longer first CR duration (P < 0.0001).

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RZ Other systems of medicine
Uncontrolled Keywords:	AcuteDisease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols ; therapeuticuse*; Child; Child Preschool; Cyclosporine; therapeuticuse*; Cytarabine / administration & dosage; Daunorubicin / administration & dosage; Disease Free Survival; Drug Administration Schedule; Etoposide; administration & dosage; Female; Humans; Immunosuppressive Agents / therapeutic use*; Leukemia Myeloid / drug therapy*; Leukemia Myeloid/mortality,Male; Middle Aged; Remission Induction / methods Substances Immunosuppressive Agents Cytarabine Etoposide Cyclosporine Daunorubicin
Additional Information:	Publication Types Clinical Trial Comparative Study Randomized Controlled Trial Full Text Sources Blackwell Publishing EBSCO Ovid Technologies, Inc. Other Literature Sources Labome Researcher Resource - ExactAntigen/Labome Molecular Biology Databases CYTARABINE - HSDB DAUNORUBICIN - HSDB ETOPOSIDE - HSDB CYCLOSPORIN A - HSDB Publication Types Clinical Trial Comparative Study Randomized Controlled Trial
Publisher:	Wiley-Blackwell
ISSN:	0007-1048
Last Modified:	25 Jun 2017 04:43
URI:	https://orca.cardiff.ac.uk/id/eprint/59141

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