Ltraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants
Ltraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants
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DOI：
10.1182/blood-2003-08-2644
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发表时间：
2004-02-15
期刊：
影响因子：
20.3
通讯作者：
Corey, L
中科院分区：
文献类型：
--
作者：
Marr, KA;Crippa, F;Corey, L
预防性氟康唑可预防念珠菌病;然而，这种药物对霉菌没有活性。我们进行了一项随机试验，以确定是否预防性伊曲康唑预防侵袭性霉菌感染（IMIs）。共有304例接受异基因干细胞移植（SCT）的患者随机接受氟康唑（400 mg/d）或伊曲康唑（口服溶液2.5 mg/kg，每日3次，或静脉注射200 mg/d），SC移植后180天，或直至移植物抗宿主病（GVHD）治疗停止后4周。通过意向治疗分析和“治疗中”分析评估潜在或可能的侵袭性真菌感染（IR）。伊曲康唑组更多的患者发生肝毒性，更多的患者因毒性或胃肠道（GI）不耐受而停用伊曲康唑（36%对16%，P <0.001）。意向治疗分析显示，在预期研究期间，IFI的发生率无差异（氟康唑16% vs伊曲康唑13%，P = 0.46）;然而，伊曲康唑组治疗期间发生IFI的患者较少（氟康唑15% vs伊曲康唑7%，P = 0.03）。伊曲康唑对IMI的保护作用更好（氟康唑12%对伊曲康唑5%，P = 0.03），但对念珠菌病的保护作用相似（3%对2%，P = 0.69）。在总体或无真菌生存期方面没有差异。伊曲康唑似乎在耐受该药物的患者亚组中预防IMI;然而，毒性和耐受性差限制了其作为预防性治疗的成功。
Prophylactic fluconazole prevents candidiasis; however, this drug has no activity against molds. We performed a randomized trial to determine whether prophylactic itraconazole prevents invasive mold infections (IMIs). A total of 304 patients receiving allogeneic stem cell transplants (SCT) were randomized to receive fluconazole (400 mg/d) or itraconazole (oral solution 2.5 mg/kg 3 times daily, or intravenous 200 mg daily) for 180 days after SC transplantation, or until 4 weeks after discontinuation of graft-versus-host disease (GVHD) therapy. Proven or probable invasive fungal infections (IR) were evaluated by intent-to-treat and "on-treatment" analyses. More patients in the itraconazole arm developed hepatotoxicities, and more patients were discontinued from itraconazole because of toxicities or gastrointestinal (GI) intolerance (36% versus 16%, P < .001). Intent-to-treat analysis demonstrated no difference in the incidence of IFI during the intended study period (fluconazole 16% versus itraconazole 13%, P = .46); however, fewer patients in the itraconazole arm developed IFI on treatment (fluconazole 15% versus itraconazole 7%, P = .03). ltraconazole provided better protection against IMI (fluconazole 12% versus itraconazole 5%, P = .03), but similar protection against candidiasis (3% versus 2%, P = .69). There was no difference in overall or fungal-free survival. ltraconazole appears to prevent IMI in the subset of patients who tolerate the drug; however, toxicities and poor tolerability limit its success as prophylactic therapy.