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

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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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/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).

Original languageEnglish
Pages (from-to)1839-1847
Number of pages9
JournalCancer Science
Volume103
Issue number10
DOIs
Publication statusPublished - 01-10-2012

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decitabine
Myelodysplastic Syndromes
Japan
Blood Cells
Subdural Hematoma
Cerebral Infarction
Myeloid Cells

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Oki, Y., Kondo, Y., Yamamoto, K., Ogura, M., Kasai, M., Kobayashi, Y., ... Tomonaga, M. (2012). Phase I/II study of decitabine in patients with myelodysplastic syndrome: A multi-center study in Japan. Cancer Science, 103(10), 1839-1847. https://doi.org/10.1111/j.1349-7006.2012.02386.x
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. / Phase I/II study of decitabine in patients with myelodysplastic syndrome : A multi-center study in Japan. In: Cancer Science. 2012 ; Vol. 103, No. 10. pp. 1839-1847.
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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/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).",
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Oki, Y, Kondo, Y, Yamamoto, K, Ogura, M, Kasai, M, Kobayashi, Y, Watanabe, T, Uike, N, Ohyashiki, K, Okamoto, SI, Ohnishi, K, Tomita, A, Miyazaki, Y, Tohyama, K, Mukai, HY, Hotta, T & Tomonaga, M 2012, 'Phase I/II study of decitabine in patients with myelodysplastic syndrome: A multi-center study in Japan', Cancer Science, vol. 103, no. 10, pp. 1839-1847. https://doi.org/10.1111/j.1349-7006.2012.02386.x

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

In: Cancer Science, Vol. 103, No. 10, 01.10.2012, p. 1839-1847.

Research output: Contribution to journalArticle

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T1 - Phase I/II study of decitabine in patients with myelodysplastic syndrome

T2 - A multi-center study in Japan

AU - Oki, Yasuhiro

AU - Kondo, Yutaka

AU - Yamamoto, Kazuhito

AU - Ogura, Michinori

AU - Kasai, Masanobu

AU - Kobayashi, Yukio

AU - Watanabe, Takashi

AU - Uike, Naokuni

AU - Ohyashiki, Kazuma

AU - Okamoto, Shin Ichiro

AU - Ohnishi, Kazunori

AU - Tomita, Akihiro

AU - Miyazaki, Yasushi

AU - Tohyama, Kaoru

AU - Mukai, Harumi Y.

AU - Hotta, Tomomitsu

AU - Tomonaga, Masao

PY - 2012/10/1

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N2 - 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).

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