Efficacy and Safety of Metronomic Chemotherapy Versus Palliative Hydroxyurea in Unfit Acute Myeloid Leukemia Patients: A Multicenter, Open-Label Randomized Controlled Trial

Document Type: Research Articles

Authors

1 Division of Hematology, Department of Internal Medicine, Udon Thani Hospital, Udon Thani, Thailand.

2 Center for Clinical Epidemiology and Clinical Statistics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

3 Division of Hematology, Department of Internal Medicine, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand.

4 Division of Hematology, Department of Internal Medicine, Si Sa Ket Hospital, Si Sa Ket, Thailand.

5 Division of Hematology, Department of Internal Medicine, Buddhachinaraj, Hospital, Phitsanulok,Thailand.

6 Division of Hematology, Department of Internal Medicine, Sawanpracharak Hospital, Nakhon Sawan,Thailand.

7 Division of Hematology, Department of Internal Medicine, Maharaj Nakhon Si Thammarat Hospital, Nakhon Si Thammarat,Thailand.

8 Division of Hematology, Department of Internal Medicine, Chonburi Hospital, Chon Buri, Thailand.

9 Division of Hematology, Department of Internal Medicine, Sanprasithiprasong Hospital, Ubon Ratchathani, Thailand.

Abstract

Background: Management of unfit AML patients is a therapeutic challenge. Most hematologists tend to avoid aggressive treatment leaving patients with a choice of best supportive care. We hypothesized that metronomic chemotherapy could be an alternative treatment for unfit AML patients. Methods: A multi-center randomized controlled trial was conducted in seven university-affiliated hospitals in Thailand. Unfit AML patients were recruited and followed up from December 2014 to December 2017. Patients were randomly assigned to receive either metronomic chemotherapy or palliative hydroxyurea. Overall survival rates were compared using Cox’s proportional hazard survival analysis.Results: A total of 81 eligible patients were randomly allocated and included for ITT analysis. The OS rate was higher in group receiving metronomic chemotherapy than in group receiving palliative treatment at 6 and 12 months with borderline significance (6 months HR 0.60; 95%CI 0.36, 1.02; p-value 0.060; 12 months: HR 0.66; 95%CI 0.41, 1.08; p-value 0.097). Conclusion: Metronomic chemotherapy could prolong survival time of unfit AML patients, especially in the first 12 months after diagnosis without increasing treatment-associated adverse events.

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