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Cancer Chemother Pharmacol. 2020 Feb 01;:
Authors: Li X, Qiu M, Wang S, Zhu H, Feng B, Zheng L
Abstract
PURPOSE: This Phase I study evaluated the safety, tolerability, food effects, pharmacodynamics, and pharmacokinetics of donafenib in patients with advanced solid tumours.
METHODS: Eligible patients received a single dose of donafenib (50 mg, 100 mg, 200 mg, 300 mg, or 400 mg) and were then observed over a 7-day period; thereafter, each patient received the corresponding dose of donafenib twice daily for at least 4 weeks. Safety assessment and pharmacokinetic sampling were performed for all patients at the given time points; preliminary tumour response was also assessed.
RESULTS: Twenty-five patients were enrolled in this study. Gastrointestinal reactions were the most common treatment-related adverse event, followed by skin toxicity. The maximum tolerated dose (MTD) was 300 mg bid. The dose-limiting toxicities (DLTs) were grade 3 diarrhoea and fatigue at 300 mg bid and grade 3 skin toxicity at 400 mg bid. In the dose range of 100 ~ 400 mg, T1/2 and AUC0-t after multiple doses were 26.9 ~ 30.2 h and 189 ~ 356 h*μg/mL, respectively. Food did not have a significant effect on the pharmacokinetics of donafenib. Twenty-one patients were assessed for efficacy, and two patients achieved a partial response according to Response Evaluation Criteria in Solid Tumors (RECIST), with a disease control rate of 57.1%.
CONCLUSION: Oral donafenib was generally well tolerated and appeared to provide some clinical benefits; adverse events were manageable. Based on the results of this study, oral donafenib at 200 mg ~ 300 mg twice daily is recommended for further studies.
PMID: 32008115 [PubMed - as supplied by publisher]
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