Phase 1 study of abemaciclib, an inhibitor of CDK 4 and 6, as a single agent for Japanese patients with advanced cancer
| Autor: | P. Kellie Turner, Edward M. Chan, Yuko Tanabe, Shunsuke Kondo, Noboru Yamamoto, Ken Ogasawara, Yutaka Fujiwara, Kenji Tamura, Hiroya Asou, Satoru Iwasa, Akihiko Shimomura, Joji Mori, Shigehisa Kitano |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_specialty Maximum Tolerated Dose Aminopyridines Antineoplastic Agents Pharmacology Toxicology QT interval 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Asian People Pharmacokinetics Cyclin-dependent kinase Neoplasms Internal medicine medicine Humans Pharmacology (medical) Abemaciclib Dose-Response Relationship Drug biology business.industry Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase 6 Middle Aged medicine.disease Treatment Outcome 030104 developmental biology chemistry Tolerability 030220 oncology & carcinogenesis Toxicity Cohort biology.protein Benzimidazoles Female business |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 78:281-288 |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | To confirm the safety and tolerability, evaluate the pharmacokinetics (PK), and investigate the antitumor activity of abemaciclib in Japanese patients with advanced cancer.We conducted a non-randomized, single-arm, open-label, dose-escalation phase 1 study of abemaciclib administered orally every 12 h (Q12H) on a 28-day cycle at doses of 100 mg (Cohort 1, n = 3), 150 mg (Cohort 2, n = 3), or 200 mg [Cohort 3, n = 6, maximum tolerated dose (MTD)]. Dose escalation was based on the frequency of dose-limiting toxicity (DLT). MTD, as established in the previous phase 1 study in non-Japanese patients, was the highest dose level at which33 % of patients experienced DLT.Eleven of the 12 patients who received treatment with abemaciclib discontinued: 10 patients due to progressive disease, and 1 due to a DLT (Cohort 3, grade 2 nausea). Diarrhea, the most common treatment-emergent adverse event (AE), was managed supportively and did not require study treatment discontinuation. There were no drug-related serious AEs and no patients with corrected QT (QTc) 480 ms or QTc change of60 ms from baseline. The abemaciclib PK profile was characterized by slow absorption and high PK variability after single or repeated doses. Two patients, one with breast cancer and one with neuroendocrine tumor, experienced30 % decrease in tumor size from baseline.In Japanese patients with advanced cancer, single-agent abemaciclib has an acceptable safety profile and demonstrates antitumor activity at a dose of 200 mg Q12H. These findings support ongoing development of abemaciclib for diverse populations with advanced cancer. |
| Databáze: | OpenAIRE |
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