title: Phase 1/2 clinical study of dasatinib in Japanese patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia.
abstract: A phase 1/2 study was conducted to assess the safety and efficacy of dasatinib in Japanese patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) resistant or intolerant to imatinib. In phase 1, 18 patients with chronic phase (CP) CML were treated with dasatinib 50, 70, or 90 mg twice daily to evaluate safety. Dasatinib <or= 90 mg twice daily was well tolerated. In phase 2, dasatinib 70 mg was given twice daily to CP-CML patients for 24 weeks and to CML patients in accelerated phase (AP)/blast crisis (BC) or Ph(+) ALL for 12 weeks. In the CP-CML group (n = 30) complete hematologic response was 90% and major cytogenetic response (MCyR) 53%. In the AP/BC-CML group (n = 11) major hematologic response (MaHR) was 64% and MCyR 27%, whereas in the Ph(+) ALL group (n = 13) MaHR was 38% and MCyR 54%. Dasatinib was well tolerated and most of the nonhematologic toxicities were mild or moderate. Dasatinib therapy resulted in high rates of hematologic and cytogenetic response, suggesting that dasatinib is promising as a new treatment for Japanese CML and Ph(+) ALL patients resistant or intolerant to imatinib.
authors.affiliation: Department of Hematology, Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. sakamaki@cick.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sakamaki
authors.affiliation: Tohoku University, Sendai, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Ishizawa
authors.affiliation: Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.affiliation: Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Fujisawa
authors.affiliation: Aichi Cancer Center, Nagoya, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.affiliation: National Cancer Center, Tokyo, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.affiliation: Hyogo Medical University, Nishinomiya, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Okada
authors.affiliation: Tokai University, Isehara, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.affiliation: Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Usui
authors.affiliation: Saiseikai Maebashi Hospital, Maebashi, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Miyawaki
authors.affiliation: Jiaikai Imamura Hospital Branch Hospital, Kagoshima, Japan.
authors.forename: Atae
authors.initials: A
authors.lastname: Utsunomiya
authors.affiliation: Matsushita Memorial Hospital, Moriguchi, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Uoshima
authors.affiliation: Jichi Medical School, Shimotsuke, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Nagoya University, Nagoya, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
authors.affiliation: Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Motoji
authors.affiliation: Saitama Medical University, Iruma, Japan.
authors.forename: Itsuro
authors.initials: I
authors.lastname: Jinnai
authors.affiliation: Okayama University, Okayama, Japan.
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.affiliation: Nagasaki University, Nagasaki, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohnishi
authors.affiliation: Nagoya City University, Nagoya, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
authors.affiliation: Keio University, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Bristol-Myers K.K., Tokyo, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Seriu
authors.affiliation: Aichi Shukutoku University, Nagoya, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ohno
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D044466:Asian People; D000069439:Dasatinib; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D013844:Thiazoles; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib