Phase 1/2 clinical study of dasatinib in Japanese patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia.
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.
Sakamaki
Hisashi
H
Department of Hematology, Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. sakamaki@cick.jp.
Ishizawa
Ken-Ichi
KI
Tohoku University, Sendai, Japan.
Taniwaki
Masafumi
M
Kyoto Prefectural University of Medicine, Kyoto, Japan.
Fujisawa
Shin
S
Yokohama City University Medical Center, Yokohama, Japan.
Morishima
Yasuo
Y
Aichi Cancer Center, Nagoya, Japan.
Tobinai
Kensei
K
National Cancer Center, Tokyo, Japan.
Okada
Masaya
M
Hyogo Medical University, Nishinomiya, Japan.
Ando
Kiyoshi
K
Tokai University, Isehara, Japan.
Usui
Noriko
N
Jikei University School of Medicine, Tokyo, Japan.
Miyawaki
Shuichi
S
Saiseikai Maebashi Hospital, Maebashi, Japan.
Utsunomiya
Atae
A
Jiaikai Imamura Hospital Branch Hospital, Kagoshima, Japan.
Uoshima
Nobuhiko
N
Matsushita Memorial Hospital, Moriguchi, Japan.
Nagai
Tadashi
T
Jichi Medical School, Shimotsuke, Japan.
Naoe
Tomoki
T
Nagoya University, Nagoya, Japan.
Motoji
Toshiko
T
Tokyo Women's Medical University, Tokyo, Japan.
Jinnai
Itsuro
I
Saitama Medical University, Iruma, Japan.
Tanimoto
Mitsune
M
Okayama University, Okayama, Japan.
Miyazaki
Yasushi
Y
Nagasaki University, Nagasaki, Japan.
Ohnishi
Kazunori
K
Hamamatsu University School of Medicine, Hamamatsu, Japan.
Iida
Shinsuke
S
Nagoya City University, Nagoya, Japan.
Okamoto
Shinichiro
S
Keio University, Tokyo, Japan.
Seriu
Taku
T
Bristol-Myers K.K., Tokyo, Japan.
Ohno
Ryuzo
R
Aichi Shukutoku University, Nagoya, Japan.
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*
D000970:Antineoplastic Agents; D011743:Pyrimidines; D013844:Thiazoles; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib