A clinical trial of voriconazole for deep-seated mycosis. An Uncontrolled Multicenter Study

Yoshihito Niki, Minoru Yoshida, Kaoru Shimada, Shigeru Kohno, Tohru Masaoka, Hideyo Yamaguchi, Naoki Aikawa, Takeshi Mori, Masahiro Andoh, Koichiro Nakata, Koichiro Kudo, Yukihiro Arai, Jin Takeuchi, Hideaki Mizoguchi, Kou Uchida, Hiroshige Mikamo, Katsunori Yanagihara, Yoshitsugu Miyazaki, Hideyuki Ikematsu, Rokuro MatsuokaKoichiro Yoshida, Akiyoshi Miwa, Shinichi Oka, Masafumi Taniwaki, Masato Watanabe, Shinji Motojima, Mitsuru Konishi, Shinichiro Okamoto, Takahide Matsuda, Takehisa Murakami, Yukata Nakashima, Tomomitsu Hotta, Yoshikazu Ito, Nobuhiko Emi, Yoshitomo Mutoh, Miki Nishimura, Kazuhiro Kimura, Tetsu Mizutani, Kensuke Usuki, Yasushi Takamatsu, Junichi Kadota, Osamu Miura, Hisashi Sakamaki, Masahiro Kami, Osamu Yamada, Hideho Wada, Noriko Usui, Masami Nagai, Yoshio Takesue, Minoru Tanaka, Fumihiko Kimura, Atsuyuki Kurashima, Masahiro Abe, Hidetoshi Igari, Takayuki Takahashi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

This was an uncontrolled multicenter study to assess the clinical usefulness (efficacy and safety) of voriconazole (VRCZ) for deep-seated mycosis. Efficacy was assessed in 65 of 100 subjects given the study drug, while safety was assessed in 100 subjects. For oral therapy, 300 mg of VRCZ was administered twice as the loading dose on Day 1, and patients then received 150-200 mg twice daily on subsequent treatment days. For intravenous therapy, 6 mg/kg of VRCZ was administered twice as the loading dose on Day 1, and the maintenance dose for subsequent treatment days was 3 mg/kg twice daily or in the case of severe mycosis, 4 mg/kg twice a day. When plasma VRCZ concentrations were equal to or greater than 2.5 μg/mL on Day 3 of oral and intravenous administration, dosages were decreased on Days 5-7. A switch from intravenous to oral formulation (switch therapy) was allowed after intravenous therapy had been given for at least 3 days. Treatment lasted 12 weeks. Global efficacy was 68.3% (28/41) for aspergillosis, 91.7% (11/12) for candidiasis, and 100% (8/8) for cryptococcosis. Global efficacy for primary therapy was 91.2% (31/34) and that for salvage therapy 61.3% (19/31). Eradication in the 65 cases evaluated for efficacy was 69.2% (9/13) for Aspergillus spp. and 91.7% (11/12) for Candida spp.. Treatment-related adverse events were reported in 78 of 100 cases. The most common adverse events were photophobia (25.0%), visual disturbance (24.0%), vomiting (8.0%), hepatic function abnormalities (8.0%), headache (8.0%), and increased γ-GTP (7.0%). Vision-related adverse events were transient and reversible in all cases. Most treatment-related adverse events were mild to moderate in severity. No relationship was seen between plasma VRCZ concentrations and either the efficacy or safety of this drug. These results indicate that VRCZ is useful for the treatment of severe or intractable deep-seated mycosis.

Original languageEnglish
Pages (from-to)32-50
Number of pages19
JournalJapanese Journal of Chemotherapy
Volume53
Issue numberSUPPL. 2
Publication statusPublished - 2005 Nov

Fingerprint

Mycoses
Multicenter Studies
Clinical Trials
Therapeutics
Safety
Voriconazole
Cryptococcosis
Salvage Therapy
Photophobia
Aspergillosis
Candidiasis
Aspergillus
Guanosine Triphosphate
Candida
Pharmaceutical Preparations
Intravenous Administration
Vomiting
Headache
Oral Administration

Keywords

  • Aspergillosis
  • Candidiasis
  • Cryptococcosis
  • Triazole antifungal agent
  • Voriconazole

ASJC Scopus subject areas

  • Pharmacology

Cite this

Niki, Y., Yoshida, M., Shimada, K., Kohno, S., Masaoka, T., Yamaguchi, H., ... Takahashi, T. (2005). A clinical trial of voriconazole for deep-seated mycosis. An Uncontrolled Multicenter Study. Japanese Journal of Chemotherapy, 53(SUPPL. 2), 32-50.

A clinical trial of voriconazole for deep-seated mycosis. An Uncontrolled Multicenter Study. / Niki, Yoshihito; Yoshida, Minoru; Shimada, Kaoru; Kohno, Shigeru; Masaoka, Tohru; Yamaguchi, Hideyo; Aikawa, Naoki; Mori, Takeshi; Andoh, Masahiro; Nakata, Koichiro; Kudo, Koichiro; Arai, Yukihiro; Takeuchi, Jin; Mizoguchi, Hideaki; Uchida, Kou; Mikamo, Hiroshige; Yanagihara, Katsunori; Miyazaki, Yoshitsugu; Ikematsu, Hideyuki; Matsuoka, Rokuro; Yoshida, Koichiro; Miwa, Akiyoshi; Oka, Shinichi; Taniwaki, Masafumi; Watanabe, Masato; Motojima, Shinji; Konishi, Mitsuru; Okamoto, Shinichiro; Matsuda, Takahide; Murakami, Takehisa; Nakashima, Yukata; Hotta, Tomomitsu; Ito, Yoshikazu; Emi, Nobuhiko; Mutoh, Yoshitomo; Nishimura, Miki; Kimura, Kazuhiro; Mizutani, Tetsu; Usuki, Kensuke; Takamatsu, Yasushi; Kadota, Junichi; Miura, Osamu; Sakamaki, Hisashi; Kami, Masahiro; Yamada, Osamu; Wada, Hideho; Usui, Noriko; Nagai, Masami; Takesue, Yoshio; Tanaka, Minoru; Kimura, Fumihiko; Kurashima, Atsuyuki; Abe, Masahiro; Igari, Hidetoshi; Takahashi, Takayuki.

In: Japanese Journal of Chemotherapy, Vol. 53, No. SUPPL. 2, 11.2005, p. 32-50.

Research output: Contribution to journalArticle

Niki, Y, Yoshida, M, Shimada, K, Kohno, S, Masaoka, T, Yamaguchi, H, Aikawa, N, Mori, T, Andoh, M, Nakata, K, Kudo, K, Arai, Y, Takeuchi, J, Mizoguchi, H, Uchida, K, Mikamo, H, Yanagihara, K, Miyazaki, Y, Ikematsu, H, Matsuoka, R, Yoshida, K, Miwa, A, Oka, S, Taniwaki, M, Watanabe, M, Motojima, S, Konishi, M, Okamoto, S, Matsuda, T, Murakami, T, Nakashima, Y, Hotta, T, Ito, Y, Emi, N, Mutoh, Y, Nishimura, M, Kimura, K, Mizutani, T, Usuki, K, Takamatsu, Y, Kadota, J, Miura, O, Sakamaki, H, Kami, M, Yamada, O, Wada, H, Usui, N, Nagai, M, Takesue, Y, Tanaka, M, Kimura, F, Kurashima, A, Abe, M, Igari, H & Takahashi, T 2005, 'A clinical trial of voriconazole for deep-seated mycosis. An Uncontrolled Multicenter Study', Japanese Journal of Chemotherapy, vol. 53, no. SUPPL. 2, pp. 32-50.
Niki Y, Yoshida M, Shimada K, Kohno S, Masaoka T, Yamaguchi H et al. A clinical trial of voriconazole for deep-seated mycosis. An Uncontrolled Multicenter Study. Japanese Journal of Chemotherapy. 2005 Nov;53(SUPPL. 2):32-50.
Niki, Yoshihito ; Yoshida, Minoru ; Shimada, Kaoru ; Kohno, Shigeru ; Masaoka, Tohru ; Yamaguchi, Hideyo ; Aikawa, Naoki ; Mori, Takeshi ; Andoh, Masahiro ; Nakata, Koichiro ; Kudo, Koichiro ; Arai, Yukihiro ; Takeuchi, Jin ; Mizoguchi, Hideaki ; Uchida, Kou ; Mikamo, Hiroshige ; Yanagihara, Katsunori ; Miyazaki, Yoshitsugu ; Ikematsu, Hideyuki ; Matsuoka, Rokuro ; Yoshida, Koichiro ; Miwa, Akiyoshi ; Oka, Shinichi ; Taniwaki, Masafumi ; Watanabe, Masato ; Motojima, Shinji ; Konishi, Mitsuru ; Okamoto, Shinichiro ; Matsuda, Takahide ; Murakami, Takehisa ; Nakashima, Yukata ; Hotta, Tomomitsu ; Ito, Yoshikazu ; Emi, Nobuhiko ; Mutoh, Yoshitomo ; Nishimura, Miki ; Kimura, Kazuhiro ; Mizutani, Tetsu ; Usuki, Kensuke ; Takamatsu, Yasushi ; Kadota, Junichi ; Miura, Osamu ; Sakamaki, Hisashi ; Kami, Masahiro ; Yamada, Osamu ; Wada, Hideho ; Usui, Noriko ; Nagai, Masami ; Takesue, Yoshio ; Tanaka, Minoru ; Kimura, Fumihiko ; Kurashima, Atsuyuki ; Abe, Masahiro ; Igari, Hidetoshi ; Takahashi, Takayuki. / A clinical trial of voriconazole for deep-seated mycosis. An Uncontrolled Multicenter Study. In: Japanese Journal of Chemotherapy. 2005 ; Vol. 53, No. SUPPL. 2. pp. 32-50.
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abstract = "This was an uncontrolled multicenter study to assess the clinical usefulness (efficacy and safety) of voriconazole (VRCZ) for deep-seated mycosis. Efficacy was assessed in 65 of 100 subjects given the study drug, while safety was assessed in 100 subjects. For oral therapy, 300 mg of VRCZ was administered twice as the loading dose on Day 1, and patients then received 150-200 mg twice daily on subsequent treatment days. For intravenous therapy, 6 mg/kg of VRCZ was administered twice as the loading dose on Day 1, and the maintenance dose for subsequent treatment days was 3 mg/kg twice daily or in the case of severe mycosis, 4 mg/kg twice a day. When plasma VRCZ concentrations were equal to or greater than 2.5 μg/mL on Day 3 of oral and intravenous administration, dosages were decreased on Days 5-7. A switch from intravenous to oral formulation (switch therapy) was allowed after intravenous therapy had been given for at least 3 days. Treatment lasted 12 weeks. Global efficacy was 68.3{\%} (28/41) for aspergillosis, 91.7{\%} (11/12) for candidiasis, and 100{\%} (8/8) for cryptococcosis. Global efficacy for primary therapy was 91.2{\%} (31/34) and that for salvage therapy 61.3{\%} (19/31). Eradication in the 65 cases evaluated for efficacy was 69.2{\%} (9/13) for Aspergillus spp. and 91.7{\%} (11/12) for Candida spp.. Treatment-related adverse events were reported in 78 of 100 cases. The most common adverse events were photophobia (25.0{\%}), visual disturbance (24.0{\%}), vomiting (8.0{\%}), hepatic function abnormalities (8.0{\%}), headache (8.0{\%}), and increased γ-GTP (7.0{\%}). Vision-related adverse events were transient and reversible in all cases. Most treatment-related adverse events were mild to moderate in severity. No relationship was seen between plasma VRCZ concentrations and either the efficacy or safety of this drug. These results indicate that VRCZ is useful for the treatment of severe or intractable deep-seated mycosis.",
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T1 - A clinical trial of voriconazole for deep-seated mycosis. An Uncontrolled Multicenter Study

AU - Niki, Yoshihito

AU - Yoshida, Minoru

AU - Shimada, Kaoru

AU - Kohno, Shigeru

AU - Masaoka, Tohru

AU - Yamaguchi, Hideyo

AU - Aikawa, Naoki

AU - Mori, Takeshi

AU - Andoh, Masahiro

AU - Nakata, Koichiro

AU - Kudo, Koichiro

AU - Arai, Yukihiro

AU - Takeuchi, Jin

AU - Mizoguchi, Hideaki

AU - Uchida, Kou

AU - Mikamo, Hiroshige

AU - Yanagihara, Katsunori

AU - Miyazaki, Yoshitsugu

AU - Ikematsu, Hideyuki

AU - Matsuoka, Rokuro

AU - Yoshida, Koichiro

AU - Miwa, Akiyoshi

AU - Oka, Shinichi

AU - Taniwaki, Masafumi

AU - Watanabe, Masato

AU - Motojima, Shinji

AU - Konishi, Mitsuru

AU - Okamoto, Shinichiro

AU - Matsuda, Takahide

AU - Murakami, Takehisa

AU - Nakashima, Yukata

AU - Hotta, Tomomitsu

AU - Ito, Yoshikazu

AU - Emi, Nobuhiko

AU - Mutoh, Yoshitomo

AU - Nishimura, Miki

AU - Kimura, Kazuhiro

AU - Mizutani, Tetsu

AU - Usuki, Kensuke

AU - Takamatsu, Yasushi

AU - Kadota, Junichi

AU - Miura, Osamu

AU - Sakamaki, Hisashi

AU - Kami, Masahiro

AU - Yamada, Osamu

AU - Wada, Hideho

AU - Usui, Noriko

AU - Nagai, Masami

AU - Takesue, Yoshio

AU - Tanaka, Minoru

AU - Kimura, Fumihiko

AU - Kurashima, Atsuyuki

AU - Abe, Masahiro

AU - Igari, Hidetoshi

AU - Takahashi, Takayuki

PY - 2005/11

Y1 - 2005/11

N2 - This was an uncontrolled multicenter study to assess the clinical usefulness (efficacy and safety) of voriconazole (VRCZ) for deep-seated mycosis. Efficacy was assessed in 65 of 100 subjects given the study drug, while safety was assessed in 100 subjects. For oral therapy, 300 mg of VRCZ was administered twice as the loading dose on Day 1, and patients then received 150-200 mg twice daily on subsequent treatment days. For intravenous therapy, 6 mg/kg of VRCZ was administered twice as the loading dose on Day 1, and the maintenance dose for subsequent treatment days was 3 mg/kg twice daily or in the case of severe mycosis, 4 mg/kg twice a day. When plasma VRCZ concentrations were equal to or greater than 2.5 μg/mL on Day 3 of oral and intravenous administration, dosages were decreased on Days 5-7. A switch from intravenous to oral formulation (switch therapy) was allowed after intravenous therapy had been given for at least 3 days. Treatment lasted 12 weeks. Global efficacy was 68.3% (28/41) for aspergillosis, 91.7% (11/12) for candidiasis, and 100% (8/8) for cryptococcosis. Global efficacy for primary therapy was 91.2% (31/34) and that for salvage therapy 61.3% (19/31). Eradication in the 65 cases evaluated for efficacy was 69.2% (9/13) for Aspergillus spp. and 91.7% (11/12) for Candida spp.. Treatment-related adverse events were reported in 78 of 100 cases. The most common adverse events were photophobia (25.0%), visual disturbance (24.0%), vomiting (8.0%), hepatic function abnormalities (8.0%), headache (8.0%), and increased γ-GTP (7.0%). Vision-related adverse events were transient and reversible in all cases. Most treatment-related adverse events were mild to moderate in severity. No relationship was seen between plasma VRCZ concentrations and either the efficacy or safety of this drug. These results indicate that VRCZ is useful for the treatment of severe or intractable deep-seated mycosis.

AB - This was an uncontrolled multicenter study to assess the clinical usefulness (efficacy and safety) of voriconazole (VRCZ) for deep-seated mycosis. Efficacy was assessed in 65 of 100 subjects given the study drug, while safety was assessed in 100 subjects. For oral therapy, 300 mg of VRCZ was administered twice as the loading dose on Day 1, and patients then received 150-200 mg twice daily on subsequent treatment days. For intravenous therapy, 6 mg/kg of VRCZ was administered twice as the loading dose on Day 1, and the maintenance dose for subsequent treatment days was 3 mg/kg twice daily or in the case of severe mycosis, 4 mg/kg twice a day. When plasma VRCZ concentrations were equal to or greater than 2.5 μg/mL on Day 3 of oral and intravenous administration, dosages were decreased on Days 5-7. A switch from intravenous to oral formulation (switch therapy) was allowed after intravenous therapy had been given for at least 3 days. Treatment lasted 12 weeks. Global efficacy was 68.3% (28/41) for aspergillosis, 91.7% (11/12) for candidiasis, and 100% (8/8) for cryptococcosis. Global efficacy for primary therapy was 91.2% (31/34) and that for salvage therapy 61.3% (19/31). Eradication in the 65 cases evaluated for efficacy was 69.2% (9/13) for Aspergillus spp. and 91.7% (11/12) for Candida spp.. Treatment-related adverse events were reported in 78 of 100 cases. The most common adverse events were photophobia (25.0%), visual disturbance (24.0%), vomiting (8.0%), hepatic function abnormalities (8.0%), headache (8.0%), and increased γ-GTP (7.0%). Vision-related adverse events were transient and reversible in all cases. Most treatment-related adverse events were mild to moderate in severity. No relationship was seen between plasma VRCZ concentrations and either the efficacy or safety of this drug. These results indicate that VRCZ is useful for the treatment of severe or intractable deep-seated mycosis.

KW - Aspergillosis

KW - Candidiasis

KW - Cryptococcosis

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