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A Phase I/II study of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph+ CML or relapsed/refractory Ph+ ALL |
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| Authors: | Arinobu Tojo Kensuke Usuki Akio Urabe Yasuhiro Maeda Yukio Kobayashi Itsuro Jinnai Kazuma Ohyashiki Miki Nishimura Tatsuya Kawaguchi Hideo Tanaka Koichi Miyamura Yasushi Miyazaki Timothy Hughes Susan Branford Shinichiro Okamoto Jun Ishikawa Masaya Okada Noriko Usui Hiromi Tanii Taro Amagasaki Hiroko Natori Tomoki Naoe |
| Affiliation: | 1. The Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo, Japan 2. NTT Kanto Medical Center, Tokyo, Japan 3. Kinki University School of Medicine, Osaka, Japan 4. National Cancer Center Hospital, Tokyo, Japan 5. International Medical Center, Saitama Medical University, Saitama, Japan 6. Tokyo Medical University Hospital, Tokyo, Japan 7. Chiba University Hospital, Chiba, Japan 8. Kumamoto University Hospital, Kumamoto, Japan 9. Hiroshima University Hospital, Hiroshima, Japan 10. Japanese Red Cross Nagoya First Hospital, Nagoya, Japan 11. Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan 12. Hanson Institute Centre for Cancer, Adelaide, Australia 13. Keio University Hospital, Tokyo, Japan 14. Osaka University Hospital, Osaka, Japan 15. The Hospital of Hyogo College of Medicine, Hyogo, Japan 16. Jikei University Hospital, Tokyo, Japan 17. Novartis Pharma Japan, Tokyo, Japan 18. Nagoya University Hospital, Aichi, Japan |
| Abstract: | 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. |
| Keywords: | Nilotinib CML BCR-ABL Imatinib resistant Ph+ ALL |
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