title: Phase I/II study of decitabine in patients with myelodysplastic syndrome: a multi-center study in Japan.
abstract: The management of myelodysplastic syndrome (MDS) remains challenging. We performed a phase I/II study to evaluate the safety and efficacy of decitabine in patients with MDS in Japan. Patients with MDS with red cell transfusion dependence or 5-30% blasts in marrow and with an International Prognostic Scoring System score of intermediate-1 or higher were eligible. Patients received intravenous decitabine at 15 or 20 mg/m(2) daily for 5 days every 4 weeks. A total of 37 patients were enrolled. Three patients received 15 mg/m(2) and experienced no dose limiting toxicity during the first cycle. Thirty-four patients received 20 mg/m(2) . Grade 3 or greater non-hematologic toxicities included cerebral infarction (n = 1), subdural hematoma (n = 1), elevated blood glucose (n = 1), and pulmonary hypertension (n = 1). At 20 mg/m(2) , complete response, partial response, and hematologic improvement were observed in 7 (20.6%), 2 (5.9%), and 7 (20.6%) patients, respectively. Complete cytogenetic response was observed in 30% of evaluable 20 patients. The median number of cycles to clinical response was 4 (range 4-8), and duration of remission was 474+ days (range 294-598+). The 2-year rate of acute myeloid leukemia-free survival was 52%. Correlative studies revealed hypomethylation in multiple genes in peripheral blood cells after treatment. Hypomethylation was generally more profound in CD15 + peripheral blood cells, which reflects myeloid cells, than in peripheral blood mononuclear cells. In summary, decitabine was safe and demonstrated efficacy in Japanese patients with high-risk MDS. This trial was registered at ClinicalTrials.gov (NCT00796003).
authors: Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan. yoki@mdanderson.org
authors: Yasuhiro
authors: Y
authors: Oki
authors: Yutaka
authors: Y
authors: Kondo
authors: Kazuhito
authors: K
authors: Yamamoto
authors: Michinori
authors: M
authors: Ogura
authors: Masanobu
authors: M
authors: Kasai
authors: Yukio
authors: Y
authors: Kobayashi
authors: Takashi
authors: T
authors: Watanabe
authors: Naokuni
authors: N
authors: Uike
authors: Kazuma
authors: K
authors: Ohyashiki
authors: Shin-ichiro
authors: S
authors: Okamoto
authors: Kazunori
authors: K
authors: Ohnishi
authors: Akihiro
authors: A
authors: Tomita
authors: Yasushi
authors: Y
authors: Miyazaki
authors: Kaoru
authors: K
authors: Tohyama
authors: Harumi Y
authors: HY
authors: Mukai
authors: Tomomitsu
authors: T
authors: Hotta
authors: Masao
authors: M
authors: Tomonaga
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine