PMID- 29893055 OWN - NLM STAT- MEDLINE DCOM- 20190325 LR - 20190325 IS - 1759-7714 (Electronic) IS - 1759-7706 (Print) IS - 1759-7706 (Linking) VI - 9 IP - 8 DP - 2018 Aug TI - Phase I safety and pharmacokinetic study of cipatinib, an original dual tyrosine kinase inhibitor. PG - 1041-1047 LID - 10.1111/1759-7714.12784 [doi] AB - BACKGROUND: Cipatinib is a novel tyrosine kinase inhibitor against both EGFR and HER2/neu. This phase I trial was conducted to assess the safety, dose-limiting toxicities (DLTs), and maximum-tolerated dose of cipatinib in HER2-positive patients with advanced breast cancer. METHODS: Eligible adults with advanced breast cancer were administered cipatinib 200 mg/day (n = 3) as an initial dose, with escalating dosages of 400 mg (n = 4), 800 mg (n = 2), 1200 mg (n = 3), 1400 mg (n = 3), 1600 mg (n = 3), and 1800 mg (n = 2) in 21 day cycles. DLTs were monitored until the end of cycle 2. Physical examinations, vital signs, blood sampling for hematology, clinical chemistry, and pharmacokinetics were performed throughout the trial. RESULTS: Of the 26 subjects enrolled, 23 completed the trial. A total of 143 adverse events (AEs) were reported, of which 87 were associated with cipatinib treatment and comprised: neutropenia (38%), hypertriglyceridemia (15%), fatigue (15%), nausea (12%), fever (19%), and myocardial ischemia (19%). Six AEs were graded 3-4 (neutropenia, increases in aspartate aminotransferase, and total bilirubin, fatigue, dizziness and nodal tachycardia), but none of the AEs observed were considered to be DLTs. CONCLUSION: This tolerability study revealed that despite a mild toxicity profile, cipatinib was well tolerated up to the anticipated maximum dosage of 1800 mg/m(2) . Further clinical trials are warranted. CI - (c) 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. FAU - Wang, Jiayu AU - Wang J AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Han, Yiqun AU - Han Y AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Shi, Xiuqing AU - Shi X AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Li, Qing AU - Li Q AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Zhang, Pin AU - Zhang P AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Yuan, Peng AU - Yuan P AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Ma, Fei AU - Ma F AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Luo, Yang AU - Luo Y AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Cai, Ruigang AU - Cai R AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Fan, Ying AU - Fan Y AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Chen, Shanshan AU - Chen S AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Li, Qiao AU - Li Q AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Xu, Binghe AU - Xu B AUID- ORCID: 0000-0002-0234-2747 AD - Department of Medical Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. LA - eng PT - Clinical Trial, Phase I PT - Journal Article DEP - 20180612 PL - Singapore TA - Thorac Cancer JT - Thoracic cancer JID - 101531441 RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) SB - IM MH - Adult MH - Breast Neoplasms/blood/*drug therapy MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Female MH - Humans MH - Maximum Tolerated Dose MH - Middle Aged MH - Protein Kinase Inhibitors/*administration & dosage/adverse effects/*pharmacokinetics MH - Quinazolines/*administration & dosage/adverse effects/*pharmacokinetics MH - Random Allocation MH - Treatment Outcome PMC - PMC6068438 OTO - NOTNLM OT - HER2 OT - Advanced breast cancer OT - RTKs OT - cipatinib OT - phase I trial EDAT- 2018/06/13 06:00 MHDA- 2019/03/26 06:00 PMCR- 2018/08/01 CRDT- 2018/06/13 06:00 PHST- 2018/04/13 00:00 [received] PHST- 2018/05/14 00:00 [revised] PHST- 2018/05/15 00:00 [accepted] PHST- 2018/06/13 06:00 [pubmed] PHST- 2019/03/26 06:00 [medline] PHST- 2018/06/13 06:00 [entrez] PHST- 2018/08/01 00:00 [pmc-release] AID - TCA12784 [pii] AID - 10.1111/1759-7714.12784 [doi] PST - ppublish SO - Thorac Cancer. 2018 Aug;9(8):1041-1047. doi: 10.1111/1759-7714.12784. Epub 2018 Jun 12.