Objective: To evaluate the efficacy and safety of itraconazole for secondary prophylaxis of previous proven or probable invasive fungal infection (IFI) in patients undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) in agranulocytosis state.
Methods: A phase IV prospective, open-label, multicenter trial was conducted to evaluate itraconazole (200 mg q12h intravenously d1-2, 200 mg/d) as secondary antifungal prophylaxis in patients (18-65 years old) undergoing chemotherapy or HSCT with previous proven or probable IFI. Itraconazole was started when patients' neutrophils＜1.5 × 10⁹/L, and stopped when chemotherapy patients' neutrophils ＞0.5 × 10⁹/L and stem cell transplant recipients' neutrophils＞1.0 × 10⁹/L. The primary end-point of the study was the incidence of proven, probable or possible IFI.
Results: Seventy one patients from November 2008 to September 2010 were enrolled in the trial. The median duration of itraconazole prophylaxis was 14 (4-35) days. No patients died of drug-related toxicity within trial. Five cases occurred IFI during the trial. The cumulative incidence of invasive fungal disease was 7.0%. One patient was withdrawn from the study due to treatment-related adverse events (liver malfunction and severe phlebitis).
Conclusion: Itraconazole appears to be safe and effective for secondary prophylaxis of systemic fungal infection after chemotherapy and allogeneic HSCT. The observed incidence of 7.0% is considerably lower than the relapse rate reported in historical controls, suggesting that itraconazole is a promising prophylactic agent in this population.
目的 对有侵袭性真菌感染（IFI）病史的血液系统疾病患者在接受化疗或造血干细胞移植处于粒细胞缺乏（粒缺）状态时予以伊曲康唑二次预防，以评估其疗效及安全性。方法 研究对象均为血液系统疾病接受化疗或造血干细胞移植患者，入组年龄18~65 岁，并在以往治疗过程中存在IFI、有现症真菌感染、严重脏器功能受损者均予以排除。所有患者均在中性粒细胞＜1.5×10⁹/L开始予以伊曲康唑二次预防，伊曲康唑静脉滴注200 mg，每日2次，第1、2天作为负荷剂量，第3天起伊曲康唑静脉针剂200 mg，每日1次，直到真菌感染危险期结束（化疗患者中性粒细胞＞0.5×10⁹/L，骨髓移植患者中性粒细胞＞1.0×10⁹/L）。主要终点是在二次预防结束时及结束7 d后突破性真菌感染的发生率。结果 2008年11月至2010年9月共有71例确诊及临床诊断的患者入组。伊曲康唑中位用药时间为14（4~35）d。5例（7.0%）预防失败，发生突破性真菌感染，感染发生率明显低于以往文献报道中无二次预防的发生率，仅1例患者因药物相关不良反应（肝功能异常及严重静脉炎）退出试验，无一例患者因药物相关不良反应死亡。结论 对既往有IFI病史的血液系统疾病患者化疗或造血干细胞移植粒缺期予以伊曲康唑二次预防是安全有效的。