Phichayut Phinyo1,2, Jayanton Patumanond3, Saranya Pongudom4. 1. Department of Family Medicine and Center for Clinical Epidemiology and Clinical Statistics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. phichayutphinyo@gmail.com. 2. Faculty of Medicine, Center for Clinical Epidemiology and Clinical Statistics, Chiang Mai University, Chiang Mai, Thailand. phichayutphinyo@gmail.com. 3. Faculty of Medicine, Center for Clinical Epidemiology and Clinical Statistics, Chiang Mai University, Chiang Mai, Thailand. 4. Department of Medicine, Udon Thani Medical Education Center, Udon Thani Hospital, Udon Thani, Thailand.
Abstract
OBJECTIVES: To examine the presence of the time-dependent effect of metronomic chemotherapy for the treatment of older patients with acute myeloid leukemia (AML) who were unfit forstandard chemotherapy and to reanalyze the data using an appropriate statistical approach in the presence of non-proportional hazards, the restricted mean survival time (RMST). RESULTS: This was a secondary analysis of a multi-center, open-label, randomized controlled trial, which was conducted in seven tertiary care hospitals across Thailand. A total of 81 unfit AML patients were randomized into two treatment groups, metronomic chemotherapy and palliative treatment. The hazard ratio of metronomic chemotherapy over palliative treatment was time-dependent. At three landmark time points of 90, 180, 365 days, the restricted mean survival time differences were 13.3 (95% CI 1.9-24.7) days, 28.9 (95% CI 3.3-54.4) days, and 40.4 (95% CI - 1.3 to 82.0) days, respectively. With non-proportional hazards modeling and RMST analysis, we were able to conclude that metronomic chemotherapy is a potentially effective alternative treatment for elderly AML patients who were medically unfit for intensive chemotherapy. In the future clinical trials, non-proportional hazards should be carefully inspected and properly handled with appropriate statistical methods. Trial registration Randomized clinical trial TCTR20150918001; registration date: 15/09/2015. Retrospectively registered.
RCT Entities:
OBJECTIVES: To examine the presence of the time-dependent effect of metronomic chemotherapy for the treatment of older patients with acute myeloid leukemia (AML) who were unfit for standard chemotherapy and to reanalyze the data using an appropriate statistical approach in the presence of non-proportional hazards, the restricted mean survival time (RMST). RESULTS: This was a secondary analysis of a multi-center, open-label, randomized controlled trial, which was conducted in seven tertiary care hospitals across Thailand. A total of 81 unfit AMLpatients were randomized into two treatment groups, metronomic chemotherapy and palliative treatment. The hazard ratio of metronomic chemotherapy over palliative treatment was time-dependent. At three landmark time points of 90, 180, 365 days, the restricted mean survival time differences were 13.3 (95% CI 1.9-24.7) days, 28.9 (95% CI 3.3-54.4) days, and 40.4 (95% CI - 1.3 to 82.0) days, respectively. With non-proportional hazards modeling and RMST analysis, we were able to conclude that metronomic chemotherapy is a potentially effective alternative treatment for elderly AMLpatients who were medically unfit for intensive chemotherapy. In the future clinical trials, non-proportional hazards should be carefully inspected and properly handled with appropriate statistical methods. Trial registration Randomized clinical trial TCTR20150918001; registration date: 15/09/2015. Retrospectively registered.
Authors: John Gregson; Linda Sharples; Gregg W Stone; Carl-Fredrik Burman; Fredrik Öhrn; Stuart Pocock Journal: J Am Coll Cardiol Date: 2019-10-22 Impact factor: 24.094