Title |
A phase 1/2 study of bosutinib in Japanese adults with Philadelphia chromosome-positive chronic myeloid leukemia
|
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Published in |
International Journal of Hematology, December 2014
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DOI | 10.1007/s12185-014-1722-8 |
Pubmed ID | |
Authors |
Chiaki Nakaseko, Naoto Takahashi, Kenichi Ishizawa, Yukio Kobayashi, Kazuteru Ohashi, Yasunori Nakagawa, Kazuhito Yamamoto, Koichi Miyamura, Masafumi Taniwaki, Masaya Okada, Tatsuya Kawaguchi, Atsushi Shibata, Yosuke Fujii, Chiho Ono, Kazunori Ohnishi |
Abstract |
This phase 1/2 study evaluated the safety and pharmacokinetics (part 1) and efficacy and safety (part 2) of bosutinib in Japanese Philadelphia chromosome-positive (Ph+) chronic-phase (CP) or advanced-phase chronic myeloid leukemia (CML) patients resistant/intolerant to previous imatinib (2L) or imatinib+dasatinib/nilotinib (3L). Based on dose-limiting toxicities and previous studies, the part 2 bosutinib starting dose was 500 mg/day (n = 63). For CP CML 2L (n = 28), the cumulative major cytogenetic response (MCyR) rate by week 24 was 36 % (primary endpoint); the cumulative major molecular response (MMR) rate through the study was 43 %. Transformation to accelerated/blast phase (AP/BP) was observed in one patient. Progression-free survival (PFS) and overall survival (OS) rates at 96 weeks were 94 and 96 %, respectively. Of seven advanced-phase 2L patients, one had confirmed complete hematologic response at week 84, and one had AP/BP transformation. PFS and OS rates at week 96 were 21 and 43 %. For 3L (n = 11), cumulative MCyR rate by week 24 was 18 %; cumulative MMR rate was 18 %; no transformations occurred. Common non-hematologic adverse events (AEs) were diarrhea (95 %), rash (57 %), and nasopharyngitis (51 %). Sixteen patients discontinued due to adverse events; no deaths occurred within 30 days of the last dose. Bosutinib 500 mg/day demonstrated efficacy and manageable toxicity in Japanese Ph+ CML patients resistant/intolerant to imatinib. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 34 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Other | 5 | 15% |
Researcher | 4 | 12% |
Professor | 4 | 12% |
Student > Bachelor | 3 | 9% |
Student > Doctoral Student | 2 | 6% |
Other | 9 | 26% |
Unknown | 7 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 12 | 35% |
Biochemistry, Genetics and Molecular Biology | 5 | 15% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
Agricultural and Biological Sciences | 2 | 6% |
Unspecified | 1 | 3% |
Other | 3 | 9% |
Unknown | 9 | 26% |