预防性伏立康唑可减少白血病化疗期的真菌感染：一项双盲试验

A double-blind trial on prophylactic voriconazole (VRC) or placebo during induction chemotherapy for acute myelogenous leukaemia (AML).
急性髓细胞白血病化疗诱导阶段预防性应用伏立康唑的一项双盲对比试验
OBJECTIVES: Invasive fungal infections remain a frequent cause of morbidity and mortality in long-term neutropenic patients.
目的：侵袭性真菌感染是长期粒缺病人的多发病和死亡的常见原因
The availability of tolerable broad-spectrum antifungals like voriconazole stimulated the discussion about optimal timing of antifungal therapy.
使用像伏立康唑那样病人可以耐受的广谱抗真菌药会引起关于抗真菌治疗治疗时间窗的争论。
We conducted a trial to analyze the efficacy and safety of voriconazole in the prevention of lung infiltrates during induction chemotherapy for acute myelogenous leukaemia (AML).
我们进行了一项临床试验旨在分析伏立康唑在急性髓细胞白血病化疗诱导阶段预防肺部浸润的有效性和安全性。
METHODS: This was a prospective, randomised, double-blind, placebo-controlled phase III trial in AML patients undergoing remission induction chemotherapy.
方法：这是一项在急性髓细胞白血病化疗诱导缓解阶段的病人中开展的前瞻、随机、双盲、安慰剂控制的三期试验
Oral voriconazole 200mg twice daily or placebo was administered until detection of a lung infiltrate or end of neutropenia.
病人每日两次口服200mg伏立康唑直至检查出肺部浸润或粒细胞缺乏结束。
Primary efficacy parameter was the incidence of lung infiltrates until day 21 after initiation of chemotherapy.
主要的有效指标为化疗开始后21天肺部浸润的发病率 。
Secondary objectives were incidence of infections, length of stay in hospital, time to antifungal treatment, time to first fever, and drug safety.
次要目标为感染发病率、住院时间、抗真菌治疗时间、首次发热时间和药物的安全性。
RESULTS: A total of 25 patients were randomly assigned to receive voriconazole (N=10) or placebo (N=15).
结果：总计25个病人随机分组接受伏立康唑（n=10）和安慰剂（n=15）。
Incidence of lung infiltrates until day 21 was 0 (0%) in the voriconazole and 5 (33%) in the placebo group (P=0.06).
至21天肺部浸润的发病率试验组为0（0%），对照组为5（33%）（P=0.06）
Average length of stay in hospital was shorter in the voriconazole group (mean 31.9days) than in the placebo group (mean 37.3days, P=0.09).
平均住院天数试验组略短，伏立康唑组（中位数31.9天），安慰剂组（中位数37.3天，P=0.09）。Four patients were diagnosed with hepatosplenic candidiasis until a 4week follow-up, all in the placebo group (P=0.11).
4位在安慰剂组的病人在其后四周的随访中被诊断出肝脾念珠菌病（P=0.01）。
Adverse events and toxicity did not differ between the two treatment groups.
在两组中的不良事件和毒性无差异。
The trial was stopped prematurely when another trial demonstrated reduced mortality by antifungal prophylaxis with posaconazole, thus rendering further randomisation against placebo unethical.
这项试验由于另一项证明预防性泊沙康唑应用可以降低死亡率的试验而提前结束，因为在这种条件下继续进行随机试验对安慰剂组违反了医学伦理。
CONCLUSION: In AML patients undergoing induction chemotherapy, prophylactic oral voriconazole 200mg twice daily resulted in trends towards reduced incidences of lung infiltrates and hepatosplenic candidiasis. Voriconazole was safe and well tolerated.
结论：急性髓细胞白血病化疗诱导阶段预防性口服一日两次200mg伏立康唑可以减低肺部浸润和肝脾念珠菌病的发病率。伏立康唑是安全且较好耐受的。