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Although hydroxyurea was associated with more dose-limiting toxicities than placebo, the agent was linked to a reduction in clinical AEs and improvements in hematological parameters, compared with placebo, in the phase 2 PIVOT trial. These results suggest hydroxyurea may be a disease-modifying therapy for patients with hemoglobin sickle cell disease (HbSC).
The phase 2 PIVOT trial randomly assigned 214 patients between 5 and 50 years of age with HbSC to hydroxyurea or a placebo. Hydroxyurea was administered at a starting dose of 20 mg/kg, with two opportunities for dose escalation during the 12-month study period. The occurrence of dose-limiting toxicities (DLTs) was the main outcome of the study. Yvonne Dei-Adomakoh, MBBS, from Korle-bu Teaching Hospital in Ghana, presented the findings1.
DLTs were more prevalent in participants on hydroxyurea than in those on placebo (33% vs 11%; Δ22%; 95% CI 11–34%), not meeting the non-inferiority threshold of 15%. Thrombocytopenia (19% vs 1%), neutropenia (13% vs 0%), and high hemoglobin (11% vs 11%) were the most reported DLTs in the study. “All cases were asymptomatic, mild, transient, and reversible,” emphasized Dr. Dei-Adomakoh. The research team observed that an older age at enrollment, a lower platelet count, and an increased spleen volume were associated with an elevated risk of developing DLTs. Interestingly, clinical AEs such as vaso occlusive pain, malaria, hospitalization, and sickle-related events were less common among patients on hydroxyurea (IRR 0.70; 95% CI 0.48–0.92).
“Although hydroxyurea was associated with more DLTs than a placebo, these events were all asymptomatic, mild, and reversible,” Dr. Dei-Adomakoh summarized in their findings. “Moreover, treatment with this drug led to fewer clinical AEs than treatment with a placebo. Since the PIVOT trial was not powered for efficacy, a phase 3 trial is needed to confirm the disease-modifying effect of hydroxyurea in HbSC.”
Medical writing support was provided by Robert van den Heuvel.
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