Phase I/II study of decitabine in patients with myelodysplastic syndrome: A multi‐center study in Japan

• Published in: Cancer science Vol. 103; no. 10; pp. 1839 - 1847
• Main Authors: Oki, Yasuhiro, Kondo, Yutaka, Yamamoto, Kazuhito, Ogura, Michinori, Kasai, Masanobu, Kobayashi, Yukio, Watanabe, Takashi, Uike, Naokuni, Ohyashiki, Kazuma, Okamoto, Shin‐ichiro, Ohnishi, Kazunori, Tomita, Akihiro, Miyazaki, Yasushi, Tohyama, Kaoru, Mukai, Harumi Y., Hotta, Tomomitsu, Tomonaga, Masao
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.10.2012
• Subjects: Aged; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - pharmacokinetics; Azacitidine - administration & dosage; Azacitidine - adverse effects; Azacitidine - analogs & derivatives; Azacitidine - pharmacokinetics; Dose-Response Relationship, Drug; Female; Humans; Japan; Male; Middle Aged; Myelodysplastic Syndromes - drug therapy; Original; Treatment Outcome; Japan
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2012.02386.x

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/m2 daily for 5 days every 4 weeks. A total of 37 patients were enrolled. Three patients received 15 mg/m2 and experienced no dose limiting toxicity during the first cycle. Thirty‐four patients received 20 mg/m2. 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/m2, 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).