Phase I and II study of azacitidine in Japanese patients with myelodysplastic syndromes

Toshiki Uchida, Yoshiaki Ogawa, Yukio Kobayashi, Takayuki Ishikawa, Haruhiko Ohashi, Tomoko Hata, Noriko Usui, Masafumi Taniwaki, Kazunori Ohnishi, Hideki Akiyama, Keiya Ozawa, Kazuma Ohyashiki, Shinichiro Okamoto, Akihiro Tomita, Shinji Nakao, Kensei Tobinai, Michinori Ogura, Kiyoshi Ando, Tomomitsu Hotta

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40 Citations (Scopus)


Azacitidine, an inhibitor of DNA methyltransferase, is reported to have antileukemic efficacy and is approved for the treatment of myelodysplastic syndromes in Western countries. We have conducted a Phase I/II study of azacitidine in Japanese patients with myelodysplastic syndromes to evaluate its pharmacokinetics, efficacy, and safety. In all, 53 patients received 75mg/m2 azacitidine subcutaneously or intravenously once daily for seven consecutive days on a 28-day cycle. The Cmax following intravenous administration was approximately 3.7-fold higher than that following subcutaneous administration, whereas the area under the plasma concentration-time curve from time zero to infinity was comparable for subcutaneous and intravenous administration. The bioavailability of azacitidine following subcutaneous administration was 91.1%, indicating that azacitidine is nearly completely absorbed after subcutaneous administration. The hematologic improvement and hematologic response rates were 54.9% (28/51) and 28.3% (15/53), respectively, and there were no differences between the two routes of administration. Azacitidine was generally well tolerated and clinically manageable in Japanese patients with myelodysplastic syndromes. Adverse events occurred in ≥20% of patients included hematologic toxicity, gastrointestinal events, and general disorders, such as malaise. Grade 3/4 adverse events that occurred in ≥50% of patients were all due to hematologic toxicity. The safety profile of azacitidine was generally similar for both routes of administration, with the exception of injection site reactions observed following subcutaneous administration. These results indicate that azacitidine can be expected to be a useful therapeutic agent in Japanese patients with myelodysplastic syndromes.

Original languageEnglish
Pages (from-to)1680-1686
Number of pages7
JournalCancer science
Issue number9
Publication statusPublished - 2011 Sept
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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