A Phase I/II study of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph plus CML or relapsed/refractory Ph plus ALL

被引：37

作者：

Tojo, Arinobu ^{[1
]}

Usuki, Kensuke ^{[2
]}

Urabe, Akio ^{[2
]}

Maeda, Yasuhiro ^{[3
]}

Kobayashi, Yukio ^{[4
]}

Jinnai, Itsuro ^{[5
]}

Ohyashiki, Kazuma ^{[6
]}

Nishimura, Miki ^{[7
]}

Kawaguchi, Tatsuya ^{[8
]}

Tanaka, Hideo ^{[9
]}

Miyamura, Koichi ^{[10
]}

Miyazaki, Yasushi ^{[11
]}

Hughes, Timothy ^{[12
]}

Branford, Susan ^{[12
]}

Okamoto, Shinichiro ^{[13
]}

Ishikawa, Jun ^{[14
]}

Okada, Masaya ^{[15
]}

Usui, Noriko ^{[16
]}

Tanii, Hiromi ^{[17
]}

Amagasaki, Taro ^{[17
]}

Natori, Hiroko ^{[17
]}

Naoe, Tomoki ^{[18
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo, Japan

[2] Nippon Telegraph & Tel Corp, Kanto Med Ctr, Tokyo, Japan

[3] Kinki Univ, Sch Med, Osaka 589, Japan

[4] Natl Canc Ctr, Tokyo, Japan

[5] Saitama Med Univ, Int Med Ctr, Saitama, Japan

[6] Tokyo Med Univ Hosp, Tokyo, Japan

[7] Chiba Univ Hosp, Chiba, Japan

[8] Kumamoto Univ Hosp, Kumamoto, Japan

[9] Hiroshima Univ Hosp, Hiroshima, Japan

[10] Japanese Red Cross Nagoya First Hosp, Nagoya, Aichi, Japan

[11] Nagasaki Univ, Hosp Med & Dent, Nagasaki 852, Japan

[12] Hanson Inst Ctr Canc, Adelaide, SA, Australia

[13] Keio Univ Hosp, Tokyo, Japan

[14] Osaka Univ Hosp, Osaka 553, Japan

[15] Hosp Hyogo, Coll Med, Hyogo, Japan

[16] Jikei Univ Hosp, Tokyo, Japan

[17] Novartis Pharma Japan, Tokyo, Japan

[18] Nagoya Univ Hosp, Aichi, Japan

来源：

INTERNATIONAL JOURNAL OF HEMATOLOGY | 2009年 / 89卷 / 05期

关键词：

Nilotinib; CML; BCR-ABL; Imatinib resistant; Ph plus ALL; CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; FORMERLY AMN107;

D O I：

10.1007/s12185-009-0327-0

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Nilotinib is a second-generation BCR-ABL kinase inhibitor with improved potency and selectivity compared to imatinib. A Phase I/II dose-escalation study was designed to evaluate the efficacy, safety, and pharmacokinetics of nilotinib in Japanese patients with imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL). A total of 34 patients were evaluated in this analysis and had a median duration of drug exposure of 293 (range 13-615) days. All 6 CML-CP patients without complete hematologic response (CHR) at baseline rapidly achieved CHR. A major cytogenetic response was achieved in 94% of patients with CML-CP, including a complete cytogenetic response in 69%. A major molecular response was achieved by 56%. These responses were also observed in patients with CML in advanced stages and Ph+ ALL. Non-hematologic adverse events were mostly mild to moderate. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 50 and 28% of patients, respectively. Overall, the results of this study suggest that nilotinib induced significant responses in imatinib-resistant or -intolerant patients with CML-CP and CML in advanced stages and Ph+ ALL. The results of this study confirmed the efficacy and safety of nilotinib in Japanese patients.

引用

页码：679 / 688

页数：10

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