Vehreschild Jörg J, Böhme Angelika, Buchheidt Dieter, Arenz Dorothee, Harnischmacher Urs, Heussel Claus P, Ullmann Andrew J, Mousset Sabine, Hummel Margit, Frommolt Peter, Wassmer Gernot, Drzisga Ivonne, Cornely Oliver A
Klinikum der Universität zu Köln, Klinik I für Innere Medizin, Studienzentrum Infektiologie II, 50937 Köln, Germany.
J Infect. 2007 Nov;55(5):445-9. doi: 10.1016/j.jinf.2007.07.003. Epub 2007 Sep 6.
Invasive fungal infections remain a frequent cause of morbidity and mortality in long-term neutropenic patients. The availability of tolerable broad-spectrum antifungals like voriconazole stimulated the discussion about optimal timing of antifungal therapy. 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).
This was a prospective, randomised, double-blind, placebo-controlled phase III trial in AML patients undergoing remission induction chemotherapy. Oral voriconazole 200 mg twice daily or placebo was administered until detection of a lung infiltrate or end of neutropenia. Primary efficacy parameter was the incidence of lung infiltrates until day 21 after initiation of chemotherapy. Secondary objectives were incidence of infections, length of stay in hospital, time to antifungal treatment, time to first fever, and drug safety.
A total of 25 patients were randomly assigned to receive voriconazole (N=10) or placebo (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). Average length of stay in hospital was shorter in the voriconazole group (mean 31.9 days) than in the placebo group (mean 37.3 days, P=0.09). Four patients were diagnosed with hepatosplenic candidiasis until a 4 week follow-up, all in the placebo group (P=0.11). Adverse events and toxicity did not differ between the two treatment groups. The trial was stopped prematurely when another trial demonstrated reduced mortality by antifungal prophylaxis with posaconazole, thus rendering further randomisation against placebo unethical.
In AML patients undergoing induction chemotherapy, prophylactic oral voriconazole 200 mg twice daily resulted in trends towards reduced incidences of lung infiltrates and hepatosplenic candidiasis. Voriconazole was safe and well tolerated.
侵袭性真菌感染仍是长期中性粒细胞减少患者发病和死亡的常见原因。伏立康唑等耐受性良好的广谱抗真菌药物的出现引发了关于抗真菌治疗最佳时机的讨论。我们进行了一项试验，以分析伏立康唑在预防急性髓性白血病（AML）诱导化疗期间肺部浸润方面的疗效和安全性。
这是一项针对接受缓解诱导化疗的AML患者的前瞻性、随机、双盲、安慰剂对照III期试验。口服伏立康唑200mg，每日两次，或给予安慰剂，直至检测到肺部浸润或中性粒细胞减少结束。主要疗效参数是化疗开始后至第21天肺部浸润的发生率。次要目标是感染发生率、住院时间、抗真菌治疗时间、首次发热时间和药物安全性。
共有25例患者被随机分配接受伏立康唑（N = 10）或安慰剂（N = 15）。伏立康唑组至第21天肺部浸润的发生率为0（0%），安慰剂组为5例（33%）（P = 0.06）。伏立康唑组的平均住院时间（平均31.9天）比安慰剂组（平均37.3天，P = 0.09）短。在4周随访期间，有4例患者被诊断为肝脾念珠菌病，均在安慰剂组（P = 0.11）。两个治疗组之间的不良事件和毒性没有差异。当另一项试验表明泊沙康唑预防性抗真菌治疗可降低死亡率时，该试验提前终止，因此继续与安慰剂进行随机对照被认为是不道德的。
在接受诱导化疗的AML患者中，每日两次口服200mg预防性伏立康唑有降低肺部浸润和肝脾念珠菌病发生率的趋势。伏立康唑安全且耐受性良好。
