10 Estimations Around BGJ398 This Year

The present study thus involved a much higher risk group of patients than those included in most other EAFT studies, which could explain the high incidence of breakthrough IA reported here. The results obtained in the present Fluconazole study show that caspofungin was the preferred first-line EAFT at our institution because, overall, it was used in 41% of febrile neutropenic episodes, which is a much higher rate than in other European centers [12]. This wide use of caspofungin is likely a result of its favourable safety profile, especially its renal safety [7]. Indeed, in the present study, liposomal AmB was switched to caspofungin in six out of ten episodes because of renal toxicity. The high rate of renal toxicity with liposomal AmB compared to the studies conducted by Walsh et?al. [7,8,13] was probably related to the use of this drug with other nephrotoxic agents in HSCT recipients. No invasive Candida infection was found in the present study, which differs from the results of other large trials that have reported breakthrough invasive infections as a result of Candida in 0.5�C3.5% of patients [7,8,13]. This discrepancy can be explained, in part, by the small size of the present study and the use of prophylactic fluconazole in 47% of our patients before EAFT. The second important observation made in the present study is the very high rate of breakthrough IA (11%) among patients receiving EAFT. Although IA cases were only probable or possible according to the EORTC/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Paclitaxel Diseases Mycoses Study Group (MSG) definition, this rate of IA is much higher than that reported in recent comparative trials among patients receiving EAFT (BGJ398 nmr IFI rates of up to 9.2% with liposomal AmB but only 1.4% with voriconazole [8]. A subgroup analysis of patients with acute myeloid leukaemia treated empirically with liposomal AmB or caspofungin, also yielded a breakthrough IFI rate of 7% in the caspofungin group and 5% in the liposomal AmB group [7]. These data also suggest that not all antifungal agents may have the same efficacy in preventing breakthrough IFIs, with better results being obtained with voriconazole and potentially worse results with caspofungin. Caspofungin is only fungistatic against Aspergillus in vitro, whereas voriconazole and liposomal AmB are fungicidal, and this might translate into lower clinical efficacy [17]. We were surprised to see all breakthrough IA cases occurring when patients were receiving EAFT with caspofungin.