Empirical voriconazole therapy for febrile neutropenic patients with hematological disorders: a prospective multicenter trial in Japan

Hideo Koh,Masaki Iino,Tohru Masaoka,Kensuke Ohta,Akihisa Kanamaru,Kazuo Tamura,Minoru Yoshida,Kazuma Ohyashiki,Jun Yamanouchi,Masayuki Hino,Akio Urabe,Fumiaki Urase,Noriko Usui,Mitsune Tanimoto,Masaki Yamaguchi

doi:10.1007/s10156-013-0634-5

Abstract

An open-label, prospective, multicenter study was conducted between October 2006 and March 2010 to assess the efficacy and safety of intravenous voriconazole (VRCZ) as empirical therapy for antibiotic-refractory febrile neutropenia in Japanese patients with hematological disorders. In addition, to find the patient groups that may benefit from antifungal therapy, the definition of invasive fungal infection proposed by EORTC/MSG (2002) was assessed in this study. Plasma (1-3)-β-d-glucan and Aspergillus PCR in blood were also measured to improve the diagnostic accuracy. A total of 103 patients (median age, 59 years), including 25 undergoing induction chemotherapies and 19 allogeneic hematopoietic cell transplants, were evaluable. Sixty-nine percent of the patients achieved resolution of clinical symptoms and 31 % achieved treatment success, defined as fulfilling the previously described five-part composite endpoint. Although VRCZ was discontinued in 9.7 % of the patients because of adverse effects, all the patients recovered soon after discontinuation of VRCZ. The treatment success rate of VRCZ appeared to be higher in patients categorized as “not classified” compared with “possible invasive fungal disease” according to the EORTC/MSG criteria. Moreover, six “not classified” patients were positive for either plasma (1-3)-β-d-glucan (n = 5) or Aspergillus PCR in blood (n = 2). The present study demonstrates that empirical VRCZ therapy is safe and effective in Japanese patients. Additionally, (1-3)-β-d-glucan and Aspergillus PCR tests were expected to provide additional information on the diagnosis of invasive fungal infections.

Highlights

An open-label, prospective, multicenter study was conducted between October 2006 and March 2010 to assess the efficacy and safety of intravenous voriconazole (VRCZ) as empirical therapy for antibiotic-refractory febrile neutropenia in Japanese patients with hematological disorders
This study strongly suggested that VRCZ reduced the incidence of documented breakthrough invasive aspergillosis, candidemia, and dematiaceous fungal infections, especially in the high-risk group without antifungal prophylaxis compared with liposomal amphotericin B [11]
A significantly low rate of breakthrough fungal infections as well as lower toxicity profiles in the VRCZ arm, demonstrated in the same study, suggest that there is no significant disadvantage to the patients when VRCZ is used instead of other established antifungals

Summary

Introduction

An open-label, prospective, multicenter study was conducted between October 2006 and March 2010 to assess the efficacy and safety of intravenous voriconazole (VRCZ) as empirical therapy for antibiotic-refractory febrile neutropenia in Japanese patients with hematological disorders. To find the patient groups that may benefit from antifungal therapy, the definition of invasive fungal infection proposed by EORTC/MSG (2002) was assessed in this study. The treatment success rate of VRCZ appeared to be higher in patients categorized as ‘‘not classified’’ compared with ‘‘possible invasive fungal disease’’ according to the EORTC/ MSG criteria. The present study demonstrates that empirical VRCZ therapy is safe and effective in Japanese patients. (1-3)-b-D-glucan and Aspergillus PCR tests were expected to provide additional information on the diagnosis of invasive fungal infections. Because an early diagnosis of IFIs remains quite difficult while a delay in antifungal therapy increases mortality, empirical antifungal therapy, triggered by persistent fever refractory to broad-spectrum antibacterial therapy, has been the standard of care for many decades [5, 6]

Methods

Results

Conclusion