TY - JOUR
T1 - Phase I and II study of azacitidine in Japanese patients with myelodysplastic syndromes
AU - Uchida, Toshiki
AU - Ogawa, Yoshiaki
AU - Kobayashi, Yukio
AU - Ishikawa, Takayuki
AU - Ohashi, Haruhiko
AU - Hata, Tomoko
AU - Usui, Noriko
AU - Taniwaki, Masafumi
AU - Ohnishi, Kazunori
AU - Akiyama, Hideki
AU - Ozawa, Keiya
AU - Ohyashiki, Kazuma
AU - Okamoto, Shinichiro
AU - Tomita, Akihiro
AU - Nakao, Shinji
AU - Tobinai, Kensei
AU - Ogura, Michinori
AU - Ando, Kiyoshi
AU - Hotta, Tomomitsu
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1349-7006.2011.01993.x
DO - 10.1111/j.1349-7006.2011.01993.x
M3 - Article
C2 - 21624006
AN - SCOPUS:80051818198
SN - 1347-9032
VL - 102
SP - 1680
EP - 1686
JO - Cancer science
JF - Cancer science
IS - 9
ER -