Efficacy and safety of short- and long-term treatment of itraconazole on chronic necrotizing pulmonary aspergillosis in multicenter study

Abstract

In the respiratory field, chronic pulmonary aspergillosis, such as chronic necrotizing pulmonary aspergillosis (CNPA) or aspergilloma, is important. We examined the efficacy and safety of short- and long-term itraconazole (ITCZ) administration, involving a switch from injection to an oral preparation, in patients with CNPA. In all hospitals participating in this study, the protocol was approved by the ethics review board. This study started after UMIN registration (UMIN000001727). Subjects enrolled in this study were patients who were clinically or definitively diagnosed with CNPA in the respiratory field, according to the diagnostic criteria of the Japanese “Guidelines for management of deep-seated mycosis 2007,” in 16 hospitals that participated in this study between May 2008 and March 2011. Treatment was started with ITCZ injection. Subsequently, the agent was switched to an oral preparation. Efficacy was evaluated with major items (clinical symptoms, fever, imaging findings) and minor items (nutritional status, inflammatory markers). Twenty-nine patients were enrolled; safety was evaluated in 24 and efficacy in 23. Of the 23 patients, 10 (43.5 %) responded. With respect to the administration period, the response rates in 8 patients treated for a short period and 15 treated for a long period were 25.0 % and 53.3 %, respectively. Trough blood concentration of ITCZ reached a level at which ITCZ may be effective for aspergillosis at 3 days after the start of ITCZ injection therapy. After changing to high-dose capsules, its level was also maintained. Adverse events such as liver dysfunction and heart failure were observed in 9 of the 24 patients. Furthermore, 6 patients died. However, there was no relationship between these events and ITCZ. Step-down therapy from ITCZ injection to oral administration may be a useful treatment option in CNPA patients requiring long-term treatment.

Appendix: Participating institutions and chief investigator of this study

Japanese Red Cross Medical Center (Tsunehiro Ando), JR Tokyo General Hospital (Tetsuo Yamaguchi), Kanto Central Hospital (Yoshio Sakamoto), Mishuku Hospital (Yoshitaka Nakamori), Mita Hospital, International University of Health and Welfare (Tetsuo Sato), National Hospital Organization Tokyo Medical Center (Yoshitaka Oyamada), Nissan Koseikai Tamagawa Hospital (Kohei Cho), Omori Red Cross Hospital (Hiroshi Tomoyasu), Showa University School of Medicine (Mitsuru Adachi, Tsukasa Ohnishi), Toho University Ohashi Medical Center (Shinya Kusachi, Ken Sanno), Toho University Omori Medical Center (Sakae Honma), Tokyo Kyosai Hospital (Jun Takagiwa), Tokyo Metropolitan Ebara Hospital (Munehide Noda), Tokyo Metropolitan Hiroo Hospital (Seiichi Nakamura), Tokyo Saiseikai Central Hospital (Fumio Sakamaki), and Toranomon Hospital (Kazuma Kishi), all in Tokyo, Japan.