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A phase I/II study of decitabine in patients with myelodysplastic syndrome: a multi-center study in Japan.
MedLine Citation:
PMID:  22816487     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 mg/m(2) 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 to 8), and duration of remission was 474+ days (range 294-598+). The two-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:
Yasuhiro Oki; Yutaka Kondo; Kazuhito Yamamoto; Michinori Ogura; Masanobu Kasai; Yukio Kobayashi; Takashi Watanabe; Naokuni Uike; Kazuma Ohyashiki; Shin-Ichiro Okamoto; Kazunori Ohnishi; Akihiro Tomita; Yasushi Miyazaki; Kaoru Tohyama; Harumi Y Mukai; Tomomitsu Hotta; Masao Tomonaga
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-21
Journal Detail:
Title:  Cancer science     Volume:  -     ISSN:  1349-7006     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Japanese Cancer Association.
Affiliation:
Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan.
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