Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial.
Background: Acute promyelocytic leukaemia is a chemotherapy-sensitive subgroup of acute myeloid leukaemia characterised by the presence of the PML-RARA fusion transcript. The present standard of care, chemotherapy and all-trans retinoic acid (ATRA), results in a high proportion of patients being cur...
| Publicado en: | Lancet Oncology Vol. 16; no. 13; pp. 1295 - 1306 |
|---|---|
| Autores principales: | , , , , , , , , , , , , , , , |
| Formato: | research randomized controlled trial Journal Article |
| Publicado: |
Elsevier B.V.
Oct2015
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=110103074&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 110103074 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14702045 KH2 jtl: Lancet Oncology issn: 14702045 maglogo: N pubinfo: dt: Oct2015 vid: 16 iid: 13 ed: 1077-4114 (Print) pid: 467 pub: Elsevier B.V. place: New York, New York artinfo: ui: 110103074 110103074 NLM26384238 110103074 10.1016/S1470-2045(15)00193-X NLM26384238 110103074 ppf: 1295 ppct: 11 formats: tig: atl: Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. aug: au: Burnett, Alan K Russell, Nigel H Hills, Robert K Bowen, David Kell, Jonathan Knapper, Steve Morgan, Yvonne G Lok, Jennie Grech, Angela Jones, Gail Khwaja, Asim Friis, Lone McMullin, Mary Frances Hunter, Ann Clark, Richard E Grimwade, David affil: Department of Haematology Cardiff University School of Medicine, Cardiff, UK sug: subj: Tretinoin Therapeutic Use Leukemia, Promyelocytic, Acute Drug Therapy Antineoplastic Agents, Combined Therapeutic Use Oxides Therapeutic Use Arsenicals Therapeutic Use Idarubicin Therapeutic Use Polymerase Chain Reaction Leukemia, Promyelocytic, Acute Diagnosis Leukemia, Promyelocytic, Acute Adult Human Leukemia, Promyelocytic, Acute Mortality Treatment Outcomes Proteins Denmark Middle Age Great Britain Quality of Life Female New Zealand Antineoplastic Agents, Combined Adverse Effects Tretinoin Adverse Effects Time Factors Arsenicals Adverse Effects Oxides Adverse Effects Young Adult Adolescence Leukocyte Count Kaplan-Meier Estimator Idarubicin Adverse Effects Male Validation Studies Comparative Studies Evaluation Research Multicenter Studies Randomized Controlled Trials Questionnaires Funding Source Adult: 19-44 years Middle Aged: 45-64 years Adolescent: 13-18 years Female Male ab: Background: Acute promyelocytic leukaemia is a chemotherapy-sensitive subgroup of acute myeloid leukaemia characterised by the presence of the PML-RARA fusion transcript. The present standard of care, chemotherapy and all-trans retinoic acid (ATRA), results in a high proportion of patients being cured. In this study, we compare a chemotherapy-free ATRA and arsenic trioxide treatment regimen with the standard chemotherapy-based regimen (ATRA and idarubicin) in both high-risk and low-risk patients with acute promyelocytic leukaemia. Methods: In the randomised, controlled, multicentre, AML17 trial, eligible patients (aged ≥16 years) with acute promyelocytic leukaemia, confirmed by the presence of the PML-RARA transcript and without significant cardiac or pulmonary comorbidities or active malignancy, and who were not pregnant or breastfeeding, were enrolled from 81 UK hospitals and randomised 1:1 to receive treatment with ATRA and arsenic trioxide or ATRA and idarubicin. ATRA was given to participants in both groups in a daily divided oral dose of 45 mg/m(2) until remission, or until day 60, and then in a 2 weeks on-2 weeks off schedule. In the ATRA and idarubicin group, idarubicin was given intravenously at 12 mg/m(2) on days 2, 4, 6, and 8 of course 1, and then at 5 mg/m(2) on days 1-4 of course 2; mitoxantrone at 10 mg/m(2) on days 1-4 of course 3, and idarubicin at 12 mg/m(2) on day 1 of the final (fourth) course. In the ATRA and arsenic trioxide group, arsenic trioxide was given intravenously at 0·3 mg/kg on days 1-5 of each course, and at 0·25 mg/kg twice weekly in weeks 2-8 of course 1 and weeks 2-4 of courses 2-5. High-risk patients (those presenting with a white blood cell count >10 × 10(9) cells per L) could receive an initial dose of the immunoconjugate gemtuzumab ozogamicin (6 mg/m(2) intravenously). Neither maintenance treatment nor CNS prophylaxis was given to patients in either group. All patients were monitored by real-time quantitative PCR. Allocation was by central computer minimisation, stratified by age, performance status, and de-novo versus secondary disease. The primary endpoint was quality of life on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 global health status. All analyses are by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN55675535. Findings: Between May 8, 2009, and Oct 3, 2013, 235 patients were enrolled and randomly assigned to ATRA and idarubicin (n=119) or ATRA and arsenic trioxide (n=116). Participants had a median age of 47 years (range 16-77; IQR 33-58) and included 57 high-risk patients. Quality of life did not differ significantly between the treatment groups (EORTC QLQ-C30 global functioning effect size 2·17 [95% CI -2·79 to 7·12; p=0·39]). Overall, 57 patients in the ATRA and idarubicin group and 40 patients in the ATRA and arsenic trioxide group reported grade 3-4 toxicities. After course 1 of treatment, grade 3-4 alopecia was reported in 23 (23%) of 98 patients in the ATRA and idarubicin group versus 5 (5%) of 95 in the ATRA and arsenic trioxide group, raised liver alanine transaminase in 11 (10%) of 108 versus 27 (25%) of 109, oral toxicity in 22 (19%) of 115 versus one (1%) of 109. After course 2 of treatment, grade 3-4 alopecia was reported in 25 (28%) of 89 patients in the ATRA and idarubicin group versus 2 (3%) of 77 in the ATRA and arsenic trioxide group; no other toxicities reached the 10% level. Patients in the ATRA and arsenic trioxide group had significantly less requirement for most aspects of supportive care than did those in the ATRA and idarubicin group. Interpretation: ATRA and arsenic trioxide is a feasible treatment in low-risk and high-risk patients with acute promyelocytic leukaemia, with a high cure rate and less relapse than, and survival not different to, ATRA and idarubicin, with a low incidence of liver toxicity. However, no improvement in quality of life was seen. pubtype: Academic Journal doctype: research randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|