Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignanciesReportar como inadecuado




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BMC Cancer

, 10:529

Clinical oncology

Abstract

BackgroundYN968D1 Apatinib selectively inhibits phosphorylation of VEGFR-2 and tumor angiogenesis in mice model. The study was conducted to determine the maximum tolerated dose MTD, safety profile, pharmacokinetic variables, and antitumor activity in advanced solid malignancies.

MethodsThis dose-escalation study was conducted according to the Chinese State Food and Drug Administration SFDA recommendations in patients with advanced solid tumors to determine the MTD for orally administered apatinib. Doses of continuously administered apatinib were escalated from 250 mg. Treatment continued after dose-escalation phase until withdrawal of consent, intolerable toxicities, disease progression or death.

ResultsForty-six patients were enrolled. Hypertension and hand-foot syndrome were the two dose-limiting toxicities noted at dose level of 1000 mg. MTD was determined to be 850 mg once daily. Pharmacokinetic analysis showed early absorption with a half-life of 9 hours. The mean half-life was constant over all dose groups. Steady-state conditions analysis suggested no accumulation during 56 days of once-daily administration. The most frequently observed drug-related adverse events were hypertension 69.5%, 29 grade 1-2 and 3 grade 3-4, proteinuria 47.8%, 16 grade 1-2 and 6 grade 3-4, and hand-foot syndrome 45.6%, 15 grade 1-2 and 6 grade 3-4. Among the thirty-seven evaluable patients, PR was noted in seven patients 18.9%, SD 24 64.9%, with a disease control rate of 83.8% at 8 weeks.

ConclusionsThe recommended dose of 750 mg once daily was well tolerated. Encouraging antitumor activity across a broad range of malignancies warrants further evaluation in selected populations.

Trial registrationClinicalTrials.gov unique identifier: NCT00633490

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-10-529 contains supplementary material, which is available to authorized users.

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Autor: Jin Li - Xinmin Zhao - Lei Chen - Haiyi Guo - Fangfang Lv - Ka Jia - Ke Yv - Fengqing Wang - Chuan Li - Jun Qian - Chunl

Fuente: https://link.springer.com/







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