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Arsenic trioxide consolidation in APL
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According to new research, addition of arsenic trioxide consolidation cycles into a multicycle chemotherapy regimen for paediatric acute pro myelocytic leukaemia is associated with improved outcomes. Matthew A Kutny (University of Alabama at Birmingham, Birmingham, AL, USA) and colleagues did a historically controlled phase 3 trial to assess the safety and outcomes after reduction of anthracycline dose plus arsenic trioxide consolidation among patients with acute promyelocytic leukaemia aged 2–21 years (n=101; 66 patients with standard-risk disease and 35 patients with high-risk disease). Patients were given two cycles of arsenic trioxide at consolidation 1, high doses of cytarabine and anthracycline at additional consolidation courses, and all-trans retinoic acid, mercaptopurine, and methotrexate at maintenance.
3-year overall survival was 94% (SD 5; 98% [3] for standard risk vs 86% [12] for high risk; p=0·003) and 3-year event-free survival was 91% (SD 6; 95% [5] for standard risk vs 83% [13] for high risk; p=0·03). The cumulative incidence of relapse at 3 years following arsenic trioxide consolidation was 4% (SD 4) and was similar in both standard-risk and high-risk patients. During consolidation 1 with arsenic trioxide, the most common adverse event was prolonged electrocardiogram corrected QT interval (QTc); grade 1 or 2 QTc interval prolongation occurred in 15 patients (16%) and 11 patients (12%), respectively, during the arsenic trioxide cycles. One patient had a grade 3 QTc interval prolongation during arsenic trioxide consolidation. Hepatic toxicity was low. Kutny said, “The incorporation of arsenic trioxide consolidation cycles
into a multi-cycle chemotherapy regimen resulted in excellent out comes for children with newly diag nosed acute promyelocytic leukemia.” Co-author Cecilia H Fu (Children’s Hospital Los Angeles, Los Angeles, CA, USA) said, “With the successful reduction in the cumulative dose of anthracyclines used in both high risk and low risk patients in this study, the late effects of anthracycline-related cardiotoxicity will also hopefully be reduced.” Anish Ray (Cook Children’s Medical Center, Fort Worth, TX, USA) commented that excellent overall survival and event-free survival were achieved in this trial, “while continuing to reduce the dose of anthracycline, exposure to which is associated with several long-term toxicities.”
H Piguet/Cnri/Science Photo Library
Arsenic trioxide consolidation in APL
Lancet Oncol 2017 Published Online August 10, 2017 http://dx.doi.org/10.1016/ S1470-2045(17)30595-8 For the study by Kutny and colleagues see J Clin Oncol 2017; published online August 2. DOI:10.1200/JCO.2016.71.6183
Manjulika Das
www.thelancet.com/oncology Published online August 10, 2017 http://dx.doi.org/10.1016/S1470-2045(17)30595-8
1
According to new research, addition of arsenic trioxide consolidation cycles into a multicycle chemotherapy regimen for paediatric acute pro myelocytic leukaemia is associated with improved outcomes. Matthew A Kutny (University of Alabama at Birmingham, Birmingham, AL, USA) and colleagues did a historically controlled phase 3 trial to assess the safety and outcomes after reduction of anthracycline dose plus arsenic trioxide consolidation among patients with acute promyelocytic leukaemia aged 2–21 years (n=101; 66 patients with standard-risk disease and 35 patients with high-risk disease). Patients were given two cycles of arsenic trioxide at consolidation 1, high doses of cytarabine and anthracycline at additional consolidation courses, and all-trans retinoic acid, mercaptopurine, and methotrexate at maintenance.
3-year overall survival was 94% (SD 5; 98% [3] for standard risk vs 86% [12] for high risk; p=0·003) and 3-year event-free survival was 91% (SD 6; 95% [5] for standard risk vs 83% [13] for high risk; p=0·03). The cumulative incidence of relapse at 3 years following arsenic trioxide consolidation was 4% (SD 4) and was similar in both standard-risk and high-risk patients. During consolidation 1 with arsenic trioxide, the most common adverse event was prolonged electrocardiogram corrected QT interval (QTc); grade 1 or 2 QTc interval prolongation occurred in 15 patients (16%) and 11 patients (12%), respectively, during the arsenic trioxide cycles. One patient had a grade 3 QTc interval prolongation during arsenic trioxide consolidation. Hepatic toxicity was low. Kutny said, “The incorporation of arsenic trioxide consolidation cycles
into a multi-cycle chemotherapy regimen resulted in excellent out comes for children with newly diag nosed acute promyelocytic leukemia.” Co-author Cecilia H Fu (Children’s Hospital Los Angeles, Los Angeles, CA, USA) said, “With the successful reduction in the cumulative dose of anthracyclines used in both high risk and low risk patients in this study, the late effects of anthracycline-related cardiotoxicity will also hopefully be reduced.” Anish Ray (Cook Children’s Medical Center, Fort Worth, TX, USA) commented that excellent overall survival and event-free survival were achieved in this trial, “while continuing to reduce the dose of anthracycline, exposure to which is associated with several long-term toxicities.”
H Piguet/Cnri/Science Photo Library
Arsenic trioxide consolidation in APL
Lancet Oncol 2017 Published Online August 10, 2017 http://dx.doi.org/10.1016/ S1470-2045(17)30595-8 For the study by Kutny and colleagues see J Clin Oncol 2017; published online August 2. DOI:10.1200/JCO.2016.71.6183
Manjulika Das
www.thelancet.com/oncology Published online August 10, 2017 http://dx.doi.org/10.1016/S1470-2045(17)30595-8
1