伊曲康唑注射液治疗血液恶性肿瘤继发真菌感染的近期疗效和安全性观察

目的观察伊曲康唑注射液治疗血液恶性肿瘤患者继发真菌感染的近期疗效和安全性。方法选择60例临床诊断的血液恶性肿瘤继发真菌感染患者作为研究对象,随机分为观察组和对照组,每组30例,观察组患者给予常规对症治疗加伊曲康唑注射液,对照组患者给予常规对症治疗加两性霉素B治疗,疗程14d。观察两组患者近期疗效和不良反应情况。结果观察组和对照组患者总有效率分别为80.0%和53.3%,两组比较差异有统计学意义(P<0.05)。两组患者各项不良反应差异均无统计学意义(P>0.05);对照组患者不良反应发生率(66.7%)高于观察组(43.3%),但差异无统计学意义(P>0.05)。结论相对两性霉素B,应用伊曲康唑治疗血液恶性肿瘤继发真菌感染的近期疗效更好,推荐在临床上应用。不良反应有待于进一步研究。     

伏立康唑和伊曲康唑治疗老年恶性肿瘤合并肺部真菌感染的疗效观察

目的评价伏立康唑和伊曲康唑治疗老年恶性肿瘤合并肺部真菌感染的临床疗效和安全性。方法回顾性分析60例老年恶性肿瘤合并肺部真菌感染患者的临床资料,其中29例患者采用伏立康唑注射液治疗(伏立康唑组),31例患者采用伊曲康唑注射液治疗(伊曲康唑组),比较两种治疗方式的临床有效率和不良反应。结果伏立康唑组患者的有效率和不良反应率发生率分别为82.8%和13.8%,伊曲康唑组患者的有效率和不良反应发生率分别为70.9%和25.8%,两组患者比较,差异有统计学意义(P<0.05)。结论伏立康唑治疗老年恶性肿瘤合并肺部真菌感染的临床疗效优于伊曲康唑,安全性好,值得临床进一步推广。     

两种药物对儿童急性白血病合并真菌感染的临床疗效观察

目的探讨泊沙康唑和伊曲康唑预防及治疗儿童急性白血病合并侵袭性真菌感染的疗效。方法回顾性分析接受常规化疗的57例白血病患儿,分别应用口服伊曲康唑及泊沙康唑预防及治疗侵袭性真菌感染,分别对两组的不良反应及临床疗效进行比较。结果泊沙康唑组CR率和总有效率均高于伊曲康唑组,但差异无统计学意义(P>0.05);泊沙康唑组不良反应发生率较伊曲康唑组增高,差异无统计学意义(P>0.05),具体不良反应方面,泊沙康唑组肝功能损害发生率明显高于伊曲康唑组,差异有统计学意义(P<0.05),而在神经毒性、视觉障碍、肾功能损害及消化道反应方面,两组间差异无统计学意义(P>0.05)。结论泊沙康唑预防及治疗侵袭性真菌感染有效率高于伊曲康唑,其肝功能损害的不良反应同时也高于伊曲康唑。     

伊曲康唑注射液治疗恶性血液病侵袭性真菌感染的临床研究

目的研究伊曲康唑注射液治疗血液恶性病患者合并侵润性真菌感染的疗效。方法对30例按标准诊断患者应用伊曲康唑注射液,剂量200~400mg/d第1天,以后200mg/d用药14天。结果临床总有效率为66.7%,确诊病例、临床诊断病例与拟诊病例有效率分别为71.3%、86.3%、25.0%。确诊病例、临床诊断病例与拟诊病例有效率之间相比,有统计学差异(P<0.05);粒细胞减少,应用广谱抗生素及糖皮质激素是发病的主要危险因素;伊曲康唑注射液起效时间3天~7天,中位时间4天。结论伊曲康唑注射液对恶性血液病合并侵袭性真菌感染疗效显著,对存在危险因素的患者早期诊断,积极治疗,可取得良好效果。     

肺癌患者化疗期间肺部真菌感染病原菌分布及使用伊曲康唑的疗效观察

目的探讨肺癌患者化疗期间肺部真菌感染病原菌分布及使用伊曲康唑的治疗效果。方法选取2016年8月至2018年12月间延安市人民医院收治的397例肺癌患者的临床资料进行回顾性分析,临床资料包括患者感染发生情况、感染病原菌及其耐药性、治疗前后中性粒细胞、炎症因子水平和肺功能等资料,并进行统计学分析。结果肺癌患者化疗期间肺部真菌感染病原菌以烟曲霉菌、新生隐球菌以及白色假丝酵母菌的感染概率最高,在感染患者中的占比分别是26. 2%、23. 8%和23. 8%。热带假丝酵母菌、光滑假丝酵母菌及毛霉菌的感染概率均较小。两性霉素B的耐药率总体高于伊曲康唑,尤其是主要感染菌烟曲霉菌、新生隐球菌以及白色假丝酵母菌对两性霉素的耐药率分别为18. 2%、10. 0%和30. 0%,均高于对伊曲康唑的耐药率,差异均有统计学意义(均P <0. 05)。患者治疗后中性粒细胞计数明显少于治疗前,而超敏C反应蛋白(hs-CRP)、降钙素原(PCT)以及白介素-6(IL-6)水平在治疗后明显比治疗前高,差异均有统计学意义(均P <0. 05)。患者治疗后最大呼气第一秒呼出气体量容积(FEV1)、用力呼气量(FVC)和FEV1/FVC各指标水平均较治疗前有大幅度提升,差异均有统计学意义(均P <0. 05)。结论肺癌患者化疗后真菌感染率较高,尤其是烟曲霉菌、新生隐球菌以及白色假丝酵母菌,且患者采用伊曲康唑治疗效果较好,可以推广应用。     

伊曲康唑序贯治疗恶性血液病合并侵袭性真菌感染的疗效分析

目的分析伊曲康唑序贯治疗恶性血液病合并侵袭性真菌感染(IFI)的疗效及安全性。方法应用伊曲康唑序贯治疗47例恶性血液病合并IFI患者,观察其有效率、退热率、肺部影像学表现及毒副反应。结果伊曲康唑序贯治疗恶性血液病合并IFI的总有效率为61.7%,临床诊断、拟诊病例的有效率分别为64.3%、62.5%;其中发热患者35例,退热率77.1%;肺部CT表现阳性者43例,炎症较前吸收者占67.4%。毒副反应主要为低钾血症、肝损伤、黄疸、恶心、味觉异常、寒战。结论伊曲康唑序贯治疗恶性血液病合并IFI疗效确切,安全性好,可作为抢先治疗和经验治疗的选择。     

恶性血液病并发呼吸道真菌感染68例诊治分析

目的 探讨恶性血液病化疗后并发呼吸道真菌感染的原因、诊治及预防。方法 对６８例合并呼吸道真菌感洒患者观察临床症状、体征、通过痰培养确诊，分析其原因。并以酮康唑、伊曲康唑、氟康唑治疗，比较疗效。结果 ６８例患者中合并念珠菌感染５８例，曲菌２例，毛霉菌８例，经用抗真菌药物治疗后，酮康唑组治愈率３８．５％，伊曲康唑组８８．９％，氟康唑组９７．３％。结论对呼吸道真菌染应注意早期预防、早期诊断、选用高效低毒     

伊曲康唑注射液治疗血液病合并侵袭性真菌病临床分析

目的：探讨伊曲康唑注射液对血液病患者合并侵袭性真菌病分层治疗的疗效及安全性。方法回顾性分析160例血液病合并侵袭性真菌病患者接受伊曲康唑注射液分层治疗的疗效和安全性,并对相关影响因素进行回顾性分析。结果伊曲康唑对全部患者的总有效率为58.12%（93／160）,其中经验治疗、诊断驱动治疗和目标治疗的有效率分别为65.82%（52／160）、53.57%（30／160）、44.00%（11／160）,三组间的疗效差异无统计学意义（P＝0.054）。相关不良事件发生率为8.13%（13／160）,主要为肝功能损害。多因素分析显示伊曲康唑注射液治疗侵袭性真菌病的疗效不受年龄、真菌感染病史、是否存在粒细胞缺乏、是否初治等因素的影响。结论伊曲康唑注射液对血液病患者合并侵袭性真菌病的各个分层治疗均有良好的疗效,且安全可靠。     

老年恶性血液病患者并发侵袭性真菌感染的临床分析

 目的　探讨老年恶性血液病患者侵袭性真菌感染（IFI）的临床特点。方法　对2000 年 1 月至2007 年10月老年恶性血液病患者IFI的临床和实验室资料进行回顾性分析。结果　7 年间共诊断老年恶性血液病患者并发IFI 38 例。IFI发病与中性粒细胞缺乏症持续时间>5 d、广谱抗生素使用时间>7 d、合并糖尿病、住院天数>20 d、使用含激素的化疗方案等因素相关。IFI临床表现随感染部位的不同和感染真菌菌种不同而异,肺部是最常见的感染部位（25例,65.8 %）。菌种主要为白色念珠菌（14株,38.9 %）、曲霉菌（7株,19.4 %）。虽经两性霉素B和伊曲康唑等抗真菌药治疗,但仍有10例患者因难以控制的呼吸衰竭死亡。结论　老年恶性血液病患者IFI发病率高、预后差,发病与多种因素有关,应及早进行预防性治疗或早期经验性抗真菌治疗。     

氟康唑预防恶性血液病患者侵袭性真菌感染疗效的Meta分析

目的:系统评价氟康唑预防恶性血液病并真菌感染的疗效。方法:计算机检索中国知网(CNKI)、万方、Pubmed、EmBase数据库,采取RevMan 5.3软件进行Meta分析。结果:共纳入研究14篇,共3 767例,氟康唑组预防真菌感染失败率高于伊曲康唑组（P＝0.001）、伏立康唑组（P＝0.009）、泊沙康唑组（P＜0.001）,较空白对照组低（P=0.006）,且差异均有统计学意义。其中氟康唑组同伊曲康唑组和泊沙康唑组进行亚组分析,分别比较了白色念珠菌、曲霉菌感染率,其中泊沙康唑组曲霉菌感染率较氟康唑组低（P＜0.000 1）,且差异有显著统计学意义。伊曲康唑组白色念珠菌感染率、曲霉菌感染率及泊沙康唑组白色念珠菌感染率差异均无显著统计学意义。结论:氟康唑能有效预防恶性血液病并真菌感染发生率,但疗效低于伊曲康唑、伏立康唑、泊沙康唑。     

Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy

BACKGROUND: The optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population. METHODS: Newly diagnosed patients with AML or high-risk MDS who were undergoing induction chemotherapy received prophylactic ABLC 2.5 mg/kg intravenously 3 times weekly. This treatment group was compared with a historical control group that had similar baseline characteristics and received prophylactic liposomal amphotericin B (L-AmB) 3 mg/kg 3 times weekly. The primary endpoint was the incidence of documented or suspected fungal infections during and up to 4 weeks after cessation of prophylaxis. Reported adverse events were used to assess tolerability. RESULTS: The overall efficacy of antifungal prophylaxis was similar in patients who received ABLC and patients who received L-AmB (P=0.95). Among 131 ABLC-treated patients and 70 L-AmB-treated patients who were assessed for efficacy and safety, 49% of patients in each group completed therapy without developing a documented or suspected fungal infection. Documented fungal infections occurred in 5% of ABLC-treated patients and in 4% of L-AmB-treated patients. Alternative antifungal strategies were required because of persistent fever or pneumonia of unknown pathogen in 28% and 32% of ABLC-treated and L-AmB-treated patients, respectively. Grade 3 and 4 adverse events, therapy discontinuations due to adverse events, and survival rates also were similar between treatment groups. CONCLUSIONS: ABLC and L-AmB appeared to have similar efficacy and were tolerated well as antifungal prophylaxis in patients with AML and high-risk MDS who were undergoing induction chemotherapy.     

Antifungal prophylaxis with itraconazole oral solution in neutropenic patients

The role of itraconazole in anti-fungal prophylaxis has been limited by the low bioavailability of the capsule formulation but the bioavailability of the oral solution is much improved. Three multi-centre studies using itraconazole solution (5 mg/kg/day) have recently been completed. The UK trial compared itraconazole solution with fluconazole suspension (100 mg/day). No invasive aspergillosis occurred in the itraconazole arm and there were more fungal deaths due to proven/suspected infection in the fluconazole group than in the itraconazole group (0 versus 7, p = 0.024). An Italian study compared itraconazole solution with placebo. Proven, suspected and superficial fungal infections were fewer in the itraconazole arm compared with placebo, with significant differences in proven and suspected systemic fungal infections (itraconazole 24% versus placebo 33%, p = 0.035). The third study compared itraconazole with amphotericin B capsules (2 g/day). There were more invasive fungal infections, Aspergillus infections and fungal deaths in the amphotericin B arm than with itraconazole but none of these differences were statistically significant. Azole prophylaxis in neutropenic patients may reduce the incidence of Candida infections, empirical amphotericin B usage, and the incidence of proven fungal infections. Itraconazole may be more effective than fluconazole in preventing invasive aspergillosis. All of these effects are more pronounced in high risk patients.     

Review of comparative studies between conventional and liposomal amphotericin B (Ambisome) in neutropenic patients with fever of unknown origin and patients with systemic mycosis

Fungal infections are an important cause of morbidity and mortality in immunocompromised patients. Treatment with amphotericin B is the main therapeutic approach. However, this treatment is limited by the substantial toxicity. We present the data of the first randomized prospective comparative trial in adults (134 patients with fever of unknown origin) with conventional amphotericin B and a liposomal formulation of amphotericin B (AmBisome, published in 1997 by Prentice et al. (Br. J. Haematol. 98, 711-718) and the data of adults with documented fungal infections (59 patients), treated in this trial. Patients received either conventional amphotericin B 1 mg kg-1 per day, liposomal amphotericin B 1 mg kg-1 per day or liposomal amphotericin B 3 mg kg-1 per day. Patients were entered if they had fever of unknown origin (FUO), defined as temperature of 38 degrees C or more, not responding to 96 h of systemic broad-spectrum antibiotic treatment, and neutropenia (< 0.5 x 10(9) l-1). Efficacy of treatment was assessed, with success defined as resolution of fever for three consecutive days (< 38 degrees C) in the group of patients with FUO and the freedom of clinical signs and/or the elimination of fungus in the group of patients with documented fungal infections. The safety of treatment and renal and hepatic toxicity of liposomal and conventional amphotericin B were compared. No statistically significant difference was found in the treatment efficacy in the three study arms. However, there is a tendency of better treatment results in the two groups of patients, who received liposomal amphotericin B. Thirty-five per cent of patients with documented fungal infections and 46% of patients with FUO responded to amphotericin B. In the patients group, that received 1 mg kg-1 liposomal amphotericin B it was 63 and 49%, in the group of patients that received 3 mg kg-1 liposomal amphotericin B it was 47 and 64%. Evidence of toxicity due to amphotericin B was seen in 50 patients (83%), toxicity due to liposomal amphotericin B, 1 mg kg-1, was seen in 35 patients (50%), and due to liposomal amphotericin B 3 mg kg-1 in 34 patients (54%). This was a statistically significant difference (P = 0.001). It was concluded that liposomal amphotericin B was safer than conventional amphotericin B, but both formulations are equivalent in treatment efficacy. The prophylactic use of amphotericin B in these immunocompromised patients is discussed.     

Prophylaxis of Fungal Infections with Itraconazole during Remission-Induction Therapy

Summary: Deep fungal infections are an increasing problem in the treatment of acute leukemias and malignant lympho-mas. Risk factors are known but unavoidable. Because of diagnostic difficulties most patients are treated empirically with intravenous amphotericin B. This drug's toxicity increases morbidity and mortality. An orally absorbable triazole derivative, itraconazole, may offer effective and safe prophylaxis against deep candidosis and aspergillosis in these patients.
Such infections have been treated successfully with oral itraconazole even when resistant to intravenous amphotericin B. In retrospective comparative studies there are significantly less deep fungal infections in patients given itraconazole. The significance of the difference varies between studies. Pharmaco-kinetic data confirm therapeutic plasma levels of itraconazole but with wide variation within and between patients.
The current large, multi-centre, randomised, double-blind, prospective trial of oral itraconazole versus placebo in the U.K. will test its prophylactic efficacy against deep fungal infections during treatment of haematological malignancies.     

Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta analysis of randomized-controlled clinical trials

BACKGROUND: The overall clinical efficacy of the azoles antifungal agents and low-dose intravenous amphotericin B for antifungal chemoprophylaxis in patients with malignant disease who have severe neutropenia remains unclear. METHODS: Randomized-controlled trials of azoles (fluconazole, itraconazole, ketoconazole, and miconazole) or intravenous amphotericin B formulations compared with placebo/no treatment or polyene-based controls in severely neutropenic chemotherapy recipients were evaluated using meta-analytical techniques. RESULTS: Thirty-eight trials that included 7014 patients (study agents, 3515 patients; control patients, 3499 patients) were analyzed. Overall, there were reductions in the use of parenteral antifungal therapy (prophylaxis success: odds ratio [OR], 0.57; 95% confidence interval [95% CI], 0.48-0.68; relative risk reduction [RRR], 19%; number requiring treatment for this outcome [NNT], 10 patients), superficial fungal infection (OR, 0.29; 95% CI, 0.20-0.43; RRR, 61%; NNT, 12 patients), invasive fungal infection (OR, 0.44; 95% CI, 0.35-0.55; RRR, 56%; NNT, 22 patients), and fungal infection-related mortality (OR, 0.58; 95% CI, 0.41-0.82; RRR, 47%; NNT, 52 patients). Invasive aspergillosis was unaffected (OR, 1.03; 95% CI, 0.62-1.44). Although overall mortality was not reduced (OR, 0.87; 95% CI, 0.74-1.03), subgroup analyses showed reduced mortality in studies of patients who had prolonged neutropenia (OR, 0.72; 95% CI, 0.55-0.95) or who underwent hematopoietic stem cell transplantation (HSCT) (OR, 0.77; 95% CI, 0.59-0.99). The multivariate metaregression analyses identified HSCT, prolonged neutropenia, acute leukemia with prolonged neutropenia, and higher azole dose as predictors of treatment effect. CONCLUSIONS: Antifungal prophylaxis reduced morbidity, as evidenced by reductions in the use of parenteral antifungal therapy, superficial fungal infection, and invasive fungal infection, as well as reducing fungal infection-related mortality. These effects were most pronounced in patients with malignant disease who had prolonged neutropenia and HSCT recipients.     

Cost-effectiveness analysis of antifungal treatment for patients on chemotherapy

Invasive fungal infections are fatal complications for patients on chemotherapy, and antifungal prophylactic treatment has been commonly recommended. Because its clinical and economic impact is not well known, we evaluated cost-effectiveness of anti-fungal treatment for patients who were neutropoenic as a result of chemotherapy. We constructed a hypothetical cohort of 40-year-old patients with acute myelogenic leukemia to evaluate years of life survived (YLS), costs (US$), and incremental cost-effectiveness ratio (US$/YLS). The following treatment strategies for fungal infections were compared: (1) prophylactic fluconazole strategy: oral fluconazole administration concurrently with chemotherapy; (2) empirical amphotericin B strategy: empirical intravenous amphotericin B administration at the point where fever is detected; and (3) no prophylaxis strategy: intravenous micafangin administration at the point where fungal infections is diagnosed. Baseline analyses showed that prophylactic fluconazole strategy involved higher costs but also longer YLSs (25,900 US$ and 24.08 YLS). The incremental cost-effectiveness ratio of prophylactic fluconazole strategy was 625 US$/YLS compared to no prophylaxis strategy, and 652 US$/YLS compared to empirical amphotericin B strategy. Baseline result was found to be robust through sensitivity analyses. Our study showed that concurrent administration of oral fluconazole during induction chemotherapy appears to ensure clinical benefits together with acceptable cost-effectiveness.     

Acute myelogenous leukemia complicated by acute necrotizing ulcerative gingivitis due to Aspergillus terreus

Infections caused by Aspergillus terreus are rare but have been associated with a poor outcome in immunocompromised patients due to frequent resistance to conventional antifungal therapy. This report describes a case of a woman who developed acute necrotizing ulcerative gingivitis (ANUG) due to A. terreus during induction chemotherapy for acute myelogenous leukemia. She initially failed to respond to treatment with amphotericin B but the infection resolved following the introduction of oral itraconazole. Opportunistic infections caused by A. terreus are an emerging problem and can be associated with a high mortality rate. Early microbiological diagnosis is critical since resistance to amphotericin B is likely and itraconazole appears to be an effective treatment for this infection.     

Antifungal treatment by amphotericin B and 5-fluorocytosine delays the recovery of normal hematopoietic cells after intensive cytostatic therapy for acute myeloid leukemia

Systemic fungal infections are recognized at increasing frequency during the course of intensive therapy for acute leukemias and require parenteral antifungal treatment mostly by amphotericin B (ampho B) alone or in combination with 5-Fluorocytosine (5-FC). Because of the potential myelosuppressive side effects of 5-FC it was the aim of the current study to evaluate the recovery of hematopoietic cells after intensive antileukemic therapy in patients receiving ampho B and 5-FC treatment for proven or suspected systemic fungal infections. The study population comprised 87 patients who were treated by standard chemotherapy for acute myeloid leukemia (AML) at first diagnosis or relapse. Twenty-two patients underwent systemic antifungal therapy consisting of ampho B (3 to 10 mg/kg/d) and 5-FC (150 mg/kg/d) for 3 to 33 days (median, 12 days). The remaining 65 patients served as controls to assess the hematologic recovery time (TR) as defined by the interval between the onset of chemotherapy and the post-treatment rise of granulocyte levels to greater than 500 cmm and thrombocyte levels to greater than 20,000 cmm. In patients receiving antifungal therapy, a significant prolongation of TR was observed with a median TR of 29 days compared with a median TR of 24 days (P = 0.0016) for the control group. No correlation was found between TR and the total dose of either ampho B or 5-FC or the type of antileukemic regimen. A possibly direct myelosuppressive effect of a fungal infection was unlikely to explain the findings because the ampho B/5-FC treatment was started in patients with proven or only suspected fungal infections, causing a similar delay of TR in both groups. The present data strongly suggest a myelosuppressive effect of ampho B/5-FC antifungal treatment in patients after intensive chemotherapy for acute leukemias.     

Brief report: practicability and safety of amphotericin B deoxycholate as continuous infusion in neutropenic patients with hematological malignancies

Fungal infections are a major cause of morbidity and mortality in patients with hematological malignancies. Candida and Aspergillus species are the most important opportunistic fungal pathogens in this patient population. Amphotericin B is the treatment of choice, but its administration is often hampered by severe side-effects, which may be reduced by continuous infusion of this drug. We describe 17 consecutive patients with hematological malignancies, suffering from fever of unknown origin with possible fungal infections, treated with amphotericin B as continuous infusion compared with a control group of 10 patients treated with conventional rapid infusion of amphotericin B over 2 - 6 h. No acute side-effects or severe nephrotoxicity were observed during continuous infusion of amphotericin B. Target doses were reached faster in patients with continuous infusion of amphotericin B than in patients with rapid infusion. We conclude that continuous infusion of amphotericin B is safe in neutropenic patients with hematological malignancies.     

Intravenous itraconazole for prophylaxis of systemic fungal infections in patients with acute myelogenous leukemia and high-risk myelodysplastic syndrome undergoing induction chemotherapy

BACKGROUND: Systemic fungal infections remain the leading cause of mortality in patients with newly diagnosed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS). The objective of the current study was to determine whether intravenous itraconazole (i.v. ITRA) reduced the incidence of probable/proven fungal infections in this group of patients, and compare the results with those of a historic control group treated with fluconazole plus itraconazole capsules (F+I). METHODS: Patients with AML and high-risk MDS who underwent induction chemotherapy received 200 mg of i.v. itraconazole over 60 minutes every 12 hours during the first 2 days followed by 200 mg given i.v. once daily. RESULTS: One hundred patients were enrolled, 96 of whom were evaluable. Approximately 48% of the patients in the group of patients treated with i.v. ITRA as well as in the F+I group completed prophylaxis. Nine patients (9%) in the study group developed either proven/probable fungal infections (Candida glabrata in 5 patients, C. tropicalis in 1 patient, C krusei in 1 patient, and Fusarium in 2 patients) compared with 3 patients (4%) with proven fungal infection in the historic control group (C. tropicalis in 1 patient and Aspergillus in 2 patients). There were no significant differences noted between the two groups with regard to the percentage of patients who developed proven/probable or possible fungal infection as well as with regard to survival. These results also were obtained after adjusting for relevant prognostic factors (creatinine and bilirubin). The most common toxicity encountered with the use of i.v. ITRA was NCI Grade 3-4 hyperbilirubinemia (6%). CONCLUSIONS: Despite its theoretic advantages, the authors found no evidence that i.v. ITRA is superior to itraconazole capsules, at least when the latter is combined with fluconazole.