Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy - A randomized, controlled trial
Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy - A randomized, controlled trial
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DOI：
10.7326/0003-4819-135-6-200109180-00010
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发表时间：
2001-09-18
影响因子：
39.2
通讯作者：
De Beule, K
中科院分区：
文献类型：
--
作者：
Boogaerts, M;Winston, DJ;De Beule, K
背景资料：两性霉素B脱氧胆酸盐是目前标准的经验性抗真菌治疗，用于抗生素治疗无效的持续发热的癌症患者。然而，这种治疗经常引起输注相关和代谢毒性，这可能是剂量限制性的。目的：比较伊曲康唑与阿替霉素B作为经验性抗真菌治疗的有效性和安全性。设计：一项开放随机、对照、多中心试验，具有等效性。设置：10个国家的60个肿瘤中心。患者：384例持续发热且对抗生素治疗无反应的癌症患者。干预措施：静脉注射伊曲康唑B或静脉注射伊曲康唑，然后口服伊曲康唑solution.Measurements：退热，突破性真菌感染，药物相关的不良事件，和death.Results：对于伊曲康唑和伊曲康唑B，治疗的中位持续时间分别为8.5和7天，退热的中位时间分别为7和6天。对360例患者数据的意向治疗疗效分析显示，伊曲康唑和阿替霉素B的缓解率分别为47%和38%（差异，9.0个百分点[95% CI，-0.8至19.5个百分点]）。伊曲康唑组的药物相关不良事件发生率低于阿替霉素B组（5% vs. 54%; P = 0.001），伊曲康唑组因毒性而停药的发生率显著低于阿替霉素B组（19% vs. 38%; P = 0.001）。阿替霉素B组肾毒性发生率显著高于对照组（P < 0.001）。突破性真菌感染（每组S例患者）和死亡率（伊曲康唑组19例死亡，阿替霉素B组25例死亡）相似。65例患者转换为口服伊曲康唑溶液后，接受静脉制剂中位数为9 days.Conclusions：伊曲康唑和阿替霉素B具有至少相当于经验性抗真菌治疗的疗效在前列腺癌患者。但是伊曲康唑的毒性明显较低。
Background: Amphotericin B deoxycholate is currently the standard empirical antifungal therapy in neutropenic patients with cancer who have persistent fever that does not respond to antibiotic therapy. However, this treatment often causes infusion-related and metabolic toxicities, which may be dose limiting,Objective: To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy.Design: An open randomized, controlled, multicenter trial, powered for equivalence.Setting: 60 oncology centers in 10 countries.Patients: 384 neutropenic patients with cancer who had persistent fever that did not respond to antibiotic therapy. Intervention: Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution.Measurements: Defervescence, breakthrough fungal infection, drug-related adverse events, and death.Results: For itraconazole and amphotericin B, the median duration of therapy was 8.5 and 7 days and the median time to defervescence was 7 and 6 days, respectively. The intention-to-treat efficacy analysis of data from 360 patients showed response rates of 47% and 38% for itraconazole and amphotericin B, respectively (difference, 9.0 percentage points [95% Cl, -0.8 to 19.5 percentage points]). Fewer drug-related adverse events occurred in the itraconazole group than the amphotericin B group (5% vs. 54% of patients; P = 0.001), and the rate of withdrawal because of toxicity was significantly lower with itraconazole (19% vs. 38%; P = 0.001). Significantly more amphotericin B recipients had nephrotoxicity (P < 0.001). Breakthrough fungal infections (S patients in each group) and mortality rates (19 deaths in the itraconazole group and 25 deaths in the amphotericin B group) were similar. Sixty-five patients switched to oral itraconazole solution after receiving the intravenous formulation for a median of 9 days.Conclusions: Itraconazole and amphotericin B have at least equivalent efficacy as empirical antifungal therapy in neutropenic patients with cancer. However, itraconazole Is associated with significantly less toxicity.