Safety, tolerability and pharmacokinetics of the fibroblast growth factor receptor inhibitor AZD4547 in Japanese patients with advanced solid tumours: a Phase I study
| العنوان: | Safety, tolerability and pharmacokinetics of the fibroblast growth factor receptor inhibitor AZD4547 in Japanese patients with advanced solid tumours: a Phase I study |
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| المؤلفون: | Chiyoe Kitagawa, Hideo Saka, Tamotsu Sagawa, Donal Landers, Yoshihito Kogure, Catherine Tchinou, Yasuhide Yamada, Koshi Fujikawa, Taro Fukao, Yasuo Takahashi, Satoru Iwasa, Naoki Takahashi |
| المصدر: | Investigational New Drugs Saka, H, Kitagawa, C, Kogure, Y, Takahashi, Y, Fujikawa, K, Sagawa, T, Iwasa, S, Takahashi, N, Fukao, T, Tchinou, C, Landers, D & Yamada, Y 2017, ' Safety, tolerability and pharmacokinetics of the fibroblast growth factor receptor inhibitor AZD4547 in Japanese patients with advanced solid tumours : a Phase I study ', Investigational new drugs, vol. 35, no. 4, pp. 451-462 . https://doi.org/10.1007/s10637-016-0416-xTest |
| بيانات النشر: | Springer US, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Receptors, Fibroblast Growth Factor/antagonists & inhibitors, Pharmacology, Gastroenterology, Piperazines, 0302 clinical medicine, Stable Disease, Phase I Studies, Neoplasms, Pharmacology (medical), Stomatitis, Manchester Cancer Research Centre, FGFR, Middle Aged, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Neoplasms/blood, Benzamides, AZD4547, Female, medicine.symptom, Safety, Half-Life, Asian Continental Ancestry Group, Adult, medicine.medical_specialty, Benzamides/adverse effects, Nausea, Antineoplastic Agents, Neutropenia, 03 medical and health sciences, Phase I, Pharmacokinetics, Asian People, Internal medicine, Pyrazoles/adverse effects, medicine, Humans, Dosing, Adverse effect, Aged, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Antineoplastic Agents/adverse effects, Piperazines/adverse effects, medicine.disease, Receptors, Fibroblast Growth Factor, Dysgeusia, 030104 developmental biology, Japanese, Pyrazoles, business |
| الوصف: | SummaryBackground AZD4547 is a potent, oral, highly selective fibroblast growth factor receptor (FGFR) inhibitor in clinical development for treating tumours with a range of FGFR aberrations, including FGFR mutations, amplifications and fusions. Methods This open-label, Phase I, multicentre study (NCT01213160) evaluated the safety, pharmacokinetics, and preliminary antitumour efficacy (RECIST v1.1) of AZD4547 monotherapy in Japanese patients with advanced solid tumours. Part A was a dose-escalation part; Part B was a dose-expansion part in patients with FGFR-amplified tumours, confirmed by fluorescence in situ hybridization. Results Thirty patients enrolled in Part A (dose range: 40 mg twice daily [bid] to 120 mg bid; 160 mg once daily [qd]), four in Part B (80 mg bid). No dose-limiting toxicities were observed and maximum tolerated dose was not determined. Most common adverse events (AEs; any grade) were: dysgeusia (50% of patients); stomatitis (41%); diarrhoea (38%); hyperphosphataemia (38%); dry mouth (35%). Common grade ≥3 AEs were nausea (12% of patients) and neutropenia (9%). No complete or partial responses were observed: 21/30 patients had stable disease ≥4 weeks in Part A, and 1/4 patients had stable disease ≥10 weeks in Part B. Following single and multiple dosing, absorption rate appeared moderate; peak plasma concentrations generally occurred 3–4 h post-dose, then declined biphasically with terminal half-life ~30 h. Steady state was reached by day 8. Compared with single dosing, plasma concentrations were, on average, 2.4- and 3.3- to 5.4-fold higher after qd and bid dosing, respectively. Conclusions AZD4547 was well tolerated in Japanese patients, with best response of stable disease ≥4 weeks. |
| اللغة: | English |
| تدمد: | 1573-0646 0167-6997 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f22f867fc4d8594943885f615cdac07dTest http://europepmc.org/articles/PMC5502072Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f22f867fc4d8594943885f615cdac07d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15730646 01676997 |
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