A randomized comparison of caspofungin versus antifungal prophylaxis according to investigator policy in acute leukaemia patients undergoing induction chemotherapy (PROFIL-C study)

Chiara Cattaneo ,Alessandro Levis ,Leonardo Campiotti ,Caterina Fanizza ,Rachele Giuliani ,Alessandra Algarotti ,Roberta Rocconi ,Gianni Tognoni ,Flavia Salvi ,Erika Borlenghi ,Giorgio Lambertenghi Deliliers ,Simona Monte ,Enrico Maria Pogliani ,Anna Salvi ,Luisa Verga ,Caterina Micò ,Elisa Cerqui ,Alessandro Rambaldi ,Ernesta Audisio ,Giuseppe Rossi

doi:10.1093/jac/dkr271

Abstract

Invasive fungal infections (IFIs) are considered a major problem among patients undergoing acute leukaemia (AL) induction treatment. PROphylaxis of Fungal invasive Infections in Leukaemia-Caspofungin (PROFIL-C) is a multicentre study aiming to assess the comparative yield of using caspofungin versus standard policy (SP) regimens and the overall impact of IFI in routine clinical care conditions. All AL patients receiving IFI prophylaxis according to local SP were prospectively included in the study by Northern Italy Leukaemia Group (NILG) centres. To allow the comparison of caspofungin versus SP regimens as prophylaxis strategies, caspofungin treatment was assigned via a centralized randomized procedure. The study was registered at http://www.clinicaltrial.gov (NCT00501098). Over a 2 year period, 175 patients were included. The overall incidence of IFI was 32/175 (18.3%) [10/175 (5.7%) probable/proven and 22/175 (12.6%) possible], with no statistically significant differences between caspofungin-based versus SP-based regimens [overall: 15/93 (16.1%) versus 17/82 (20.7%), relative risk (RR) 0.78, 95% confidence interval (CI) 0.42-1.46; probable/proven: 7/93 (7.5%) versus 3/82 (3.7%), RR 2.06, 95% CI 0.55-7.7; possible: 8/93 (8.6%) versus 14/82 (17.1%), RR 0.5, 95% CI 0.22-1.14]. Only one IFI-related death was recorded (10%). The incidence and mortality of IFI were lower than expected in this strictly sequential cohort representative of the routine care in the NILG network. The efficacy and safety of caspofungin were similar to other prophylactic regimens.

Highlights

The need for antifungal prophylaxis to prevent invasive fungal infections (IFIs) in haematological patients is still debatable, considering its potential role in inducing resistant strains and impairing the diagnostic accuracy of Aspergillus galactomannan (GM) antigen detection and its cost – efficacy ratio.[1,2] On the other hand, a recent meta-analysis[3] showed a reduction of mortality among cancer patients receiving antifungal prophylaxis
The safety and tolerability of caspofungin have been proven both as empirical therapy during neutropenia by Walsh et al.[11] and as primary prophylaxis in patients undergoing haematopoietic stem cell transplantation (HSCT) by Chou et al.[12]
The PROFIL-C study was implemented from January 2007 to January 2009 as a multicentre Phase II parallel group study with a randomized comparison (1:1) between caspofungin and standard policy (SP) regimens

Summary

Introduction

The need for antifungal prophylaxis to prevent invasive fungal infections (IFIs) in haematological patients is still debatable, considering its potential role in inducing resistant strains and impairing the diagnostic accuracy of Aspergillus galactomannan (GM) antigen detection and its cost – efficacy ratio.[1,2] On the other hand, a recent meta-analysis[3] showed a reduction of mortality among cancer patients receiving antifungal prophylaxis. The interest of focusing on caspofungin as a prophylactic agent was motivated by its spectrum of action against Candida spp. and Aspergillus spp., its safety record and the lack of Invasive mycoses during acute leukaemia induction. Invasive fungal infections (IFIs) are considered a major problem among patients undergoing acute leukaemia (AL) induction treatment. PROphylaxis of Fungal invasive Infections in Leukaemia-Caspofungin (PROFIL-C) is a multicentre study aiming to assess the comparative yield of using caspofungin versus standard policy (SP) regimens and the overall impact of IFI in routine clinical care conditions

Methods

Results

Conclusion