Article
Version 1
This version is not peer-reviewed
Hydroxyurea: An Old Drug in Need of New Clinical Trials in Myeloproliferative Neoplasms
Version 1
: Received: 3 August 2024 / Approved: 5 August 2024 / Online: 5 August 2024 (14:31:12 CEST)
How to cite: Manoharan, A.; Enggist, S. Hydroxyurea: An Old Drug in Need of New Clinical Trials in Myeloproliferative Neoplasms. Preprints 2024, 2024080323. https://doi.org/10.20944/preprints202408.0323.v1 Manoharan, A.; Enggist, S. Hydroxyurea: An Old Drug in Need of New Clinical Trials in Myeloproliferative Neoplasms. Preprints 2024, 2024080323. https://doi.org/10.20944/preprints202408.0323.v1
Abstract
ABSTRACT Hydroxyurea (Hu) has been a front-line therapeutic agent for myeloproliferative neoplasms (MPN) for many years and still enjoys the endorsement of experts in the field. However, several publications have reported sub-optimal response, the need for treatment interruption because of cytopenias and lack of sustained response. In all these studies, Hu was used as continuous therapy at a daily dose ranging from 500mg to 3000mg. At our Centre we have used Hu as intermittent therapy (akin to schedules used in patients with solid tumours) at 20-30mg/Kg doses, given as a single dose, twice or thrice weekly. We have consistently observed sustained responses without troublesome cytopenias. In this report we present our experience in 118 patients treated with intermittent Hu during the past 30 years (median follow-up 8.5 yrs): polycythemia vera – 29; essential thrombocythemia – 84; primary myelofibrosis – 5. Based on the pharmacokinetics of Hu and our experience, we speculate that the efficacy of intermittent Hu therapy without troublesome myelotoxicity over long periods of time is attributable to the following: i) higher plasma level from intake of Hu as a single dose; ii) higher uptake of Hu by cells with higher mitotic activity (i.e. the abnormal clone); and iii) unhindered, normal haemopoiesis on the drug free days each week. We hope that this article will generate interest and contemplation, leading to randomized clinical studies to compare the two dosage schedules (Continuous Vs Intermittent) in MPN patients.
Keywords
hydroxyurea; continuous therapy; intermittent therapy
Subject
Medicine and Pharmacology, Hematology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comments (0)
We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.
Leave a public commentSend a private comment to the author(s)
* All users must log in before leaving a comment