Sakamaki Hisashi, Ishizawa Ken-Ichi, Taniwaki Masafumi, Fujisawa Shin, Morishima Yasuo, Tobinai Kensei, Okada Masaya, Ando Kiyoshi, Usui Noriko, Miyawaki Shuichi, Utsunomiya Atae, Uoshima Nobuhiko, Nagai Tadashi, Naoe Tomoki, Motoji Toshiko, Jinnai Itsuro, Tanimoto Mitsune, Miyazaki Yasushi, Ohnishi Kazunori, Iida Shinsuke, Okamoto Shinichiro, Seriu Taku, Ohno Ryuzo
Department of Hematology, Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.
Tohoku University, Sendai, Japan.
Int J Hematol. 2009 Apr;89(3):332-341. doi: 10.1007/s12185-009-0260-2. Epub 2009 Mar 5.
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.
开展了一项1/2期研究，以评估达沙替尼对日本慢性髓性白血病（CML）或对伊马替尼耐药或不耐受的费城染色体阳性急性淋巴细胞白血病（Ph(+) ALL）患者的安全性和疗效。在1期研究中，18例慢性期（CP）CML患者接受每日两次50、70或90 mg达沙替尼治疗，以评估安全性。每日两次达沙替尼≤90 mg耐受性良好。在2期研究中，每日两次给予CP-CML患者70 mg达沙替尼，持续24周，给予加速期（AP）/急变期（BC）CML患者或Ph(+) ALL患者12周。在CP-CML组（n = 30）中，完全血液学缓解率为90%，主要细胞遗传学缓解（MCyR）率为53%。在AP/BC-CML组（n = 11）中，主要血液学缓解（MaHR）率为64%，MCyR率为27%，而在Ph(+) ALL组（n = 13）中，MaHR率为38%，MCyR率为54%。达沙替尼耐受性良好，大多数非血液学毒性为轻度或中度。达沙替尼治疗导致血液学和细胞遗传学缓解率较高，表明达沙替尼有望成为对伊马替尼耐药或不耐受的日本CML和Ph(+) ALL患者的一种新治疗方法。
