Olanzapine Versus Haloperidol for Treatment of Delirium in Patients with Advanced Cancer: A Phase III Randomized Clinical Trial

The oncologist

article

Maurice J.D.L. van der Vorst¹  Wouter W.A. Zuurmond³  Henk M.W. Verheul¹  Elisabeth C.W. Neefjes¹  Manon S.A. Boddaert⁵  Bea A.T.T. Verdegaal¹  Aart Beeker²  Saskia C.C. Teunissen⁶  Aartjan T.F. Beekman⁸  Janneke A. Wilschut⁹  Johannes Berkhof⁹ 

[1] Department of Medical Oncology, Cancer Center Amsterdam, Vrije Universiteit Amsterdam;Department of Internal Medicine, Rijnstate Hospital;Department of Anesthesiology, Vrije Universiteit;Hospice Kuria;Netherlands Comprehensive Cancer Organisation (IKNL);Department of General Practice, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht;Academic Hospice Demeter;Department of Psychiatry, Vrije Universiteit Amsterdam;Department of Epidemiology and Biostatistics, Vrije Universiteit Amsterdam

关键词: Delirium;    Advanced cancer;    Haloperidol;    Olanzapine;    Efficacy;    Safety;    Phase III;   

DOI  :  10.1634/theoncologist.2019-0470

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background Treatment of delirium often includes haloperidol. Second-generation antipsychotics like olanzapine have emerged as an alternative with possibly fewer side effects. The aim of this multicenter, phase III, randomized clinical trial was to compare the efficacy and tolerability of olanzapine with haloperidol for the treatment of delirium in hospitalized patients with advanced cancer. Materials and Methods Eligible adult patients (≥18 years) with advanced cancer and delirium (Delirium Rating Scale-Revised-98 [DRS-R-98] total score ≥17.75) were randomized 1:1 to receive either haloperidol or olanzapine (age-adjusted, titratable doses). Primary endpoint was delirium response rate (DRR), defined as number of patients with DRS-R-98 severity score <15.25 and ≥4.5 points reduction. Secondary endpoints included time to response (TTR), tolerability, and delirium-related distress. Results Between January 2011 and June 2016, 98 patients were included in the intention-to-treat analysis. DRR was 45% (95% confidence interval [CI], 31–59) for olanzapine and 57% (95% CI, 43–71) for haloperidol (Δ DRR −12%; odds ratio [OR], 0.61; 95% CI, 0.2–1.4; p = .23). Mean TTR was 4.5 days (95% CI, 3.2–5.9 days) for olanzapine and 2.8 days (95% CI, 1.9–3.7 days; p = .18) for haloperidol. Grade ≥3 treatment-related adverse events occurred in 5 patients (10.2%) and 10 patients (20.4%) in the olanzapine and haloperidol arm, respectively. Distress rates were similar in both groups. The study was terminated early because of futility. Conclusion Delirium treatment with olanzapine in hospitalized patients with advanced cancer did not result in improvement of DRR or TTR compared with haloperidol. Clinical trial identification number . NCT01539733. Dutch Trial Register . NTR2559. Implications for Practice Guidelines recommend that pharmacological interventions for delirium treatment in adults with cancer should be limited to patients who have distressing delirium symptoms. It was suggested that atypical antipsychotics, such as olanzapine, outperform haloperidol in efficacy and safety. However, collective data comparing the efficacy and safety of typical versus atypical antipsychotics in patients with cancer are limited. If targeted and judicious use of antipsychotics is considered for the treatment of delirium in patients with advanced cancer, this study demonstrated that there was no statistically significant difference in response to haloperidol or olanzapine. Olanzapine showed an overall better safety profile compared with haloperidol, although this difference was not statistically significant.

【 授权许可】

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