Phase I safety and pharmacokinetic study of cipatinib, an original dual tyrosine kinase inhibitor. Issue 8 (12th June 2018)

• Record Type: Journal Article
• Authors: Wang, Jiayu; Han, Yiqun; Shi, Xiuqing; Li, Qing; Zhang, Pin; Yuan, Peng; Ma, Fei; Luo, Yang; Cai, Ruigang; Fan, Ying; Chen, Shanshan; Li, Qiao; Xu, Binghe
• Is Part Of: Thoracic cancer. Volume 9:Issue 8(2018)
• Page Start: 1041
• Page End: 1047
• Publication Date: 2018-06-12
• Subjects: Advanced breast cancer -- cipatinib -- HER2 -- phase I trial -- RTKs; Chest -- Cancer -- Periodicals; Chest -- Cancer -- Treatment -- Periodicals; Chest -- Surgery -- Periodicals; 616.99494005
• DOI: 10.1111/1759-7714.12784
• Languages: English
• ISSNs: 1759-7706

Abstract

Abstract : 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.