A prospective, randomized study of empirical antifungal therapy for the treatment of chemotherapy‐induced febrile neutropenia in children

Abstract

SummaryGiven that the rationale for empirical antifungal therapy in neutropenic children is limited and based on adult patient data, we performed a prospective, randomized, controlled trial that evaluated 110 neutropenic children with persistent fever. Those at high risk for invasive fungal infections (IFI) received caspofungin (Arm C) or liposomal amphotericinB (Arm B); those with a lower risk were randomized to receive Arm B, C, or no antifungal treatment (Arm A). Complete response to empirical antifungal therapy was achieved in 90/104 patients (86·5%): 48/56 at high risk (85·7%) [88·0% in Arm B; 83·9% in Arm C (P = 0·72)], and 42/48 at low risk (87·5%) [87·5% in control Arm A, 80·0% Arm B, 94·1% Arm C; (P = 0·41)]. None of the variables tested by multiple logistic regression analysis showed a significant effect on the probability to achieve complete response. IFI was diagnosed in nine patients (8·2%, 95% confidence interval, 3·8-15·0). This randomized controlled study showed that empirical antifungal therapy was of no advantage in terms of survival without fever and IFI in patients aged <18 years and defined with low risk of IFI. Higher risk patients, including those with relapsed cancer, appear to be the target for empirical antifungal therapy during protracted febrile neutropenia.

Efficacy and safety of caspofungin in children: systematic review and meta-analysis

“…The direction of the effect of two of them (Maertens 4 and Mohamed 7 ) suggests that caspofungin is more effective than amphotericin. However, in the study of Caselli et al, 5 the difference is almost null. The overall summary measure (RR 1.47) shows a direction of the effect favoring caspofungin, but without the necessary accuracy to be able to assert it (CI 95%: 0.78-2.79).…”

“…[1][2][3][4] This review is timely because it explains why the use of In one of them, caspofungin was more effective than amphotericin; 4 in another one, the direction of the effect favored caspofungin but without enough accuracy; 7 while in the third one, the direction was almost null. 5 The common summary measure keeps a direction of the effect in favor of caspofungin but with a significant uncertainty that does not allow to ascertain it.…”

“…3) A multicentric and randomized study published by Caselli et al, 5 analyzed 110 neutropenic children (undergoing chemotherapy or autologous bone marrow transplantation) with persistent fever on day 4 in spite of antibiotic treatment and, consequently, with risk of having an IFI. Follow-up was extended to at least 30 days.…”

“…It has been shown that caspofungin is effective in esophageal and in invasive candidiasis, as rescue therapy in aspergillosis and as empirical therapy of neutropenia and fever in adults. 5 It is important to point out that its resistance potential is low. Its apparent low toxicity and the lack of interactions make caspofungin a useful alternative in fungal infection prophylaxis and treatment.…”

“…In spite of having been approved by the Food and Drug Administration (FDA) for its use in children aged 3 months and older, the experience in children is still limited. 4,5 T h e n e e d t o h a v e t r e a t m e n t alternatives available, of proven effectiveness and safety, to manage IFIs among children, and the limited experience with the use of caspofungin in our setting, explains the objective of this study, in which a systematic review about caspofungin effectiveness a n d s a f e t y w a s c o n d u c t e d , i n comparison with standard antifungal agents, to manage the prophylaxis and/or treatment of proven, probable or possible IFIs in children.…”