凡德他尼联合mFOLFOX6用于晚期结直肠癌患者的开放标签I期试验。
Open-label phase I trial of vandetanib in combination with mFOLFOX6 in patients with advanced colorectal cancer.
作者信息
Michael Michael, Gibbs Peter, Smith Robert, Godwood Alex, Oliver Stuart, Tebbutt Niall
机构信息
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria, 3002, Australia.
出版信息
Invest New Drugs. 2009 Jun;27(3):253-61. doi: 10.1007/s10637-008-9182-8. Epub 2008 Nov 11.
BACKGROUND
Vandetanib (ZACTIMA) is a once-daily oral inhibitor of vascular endothelial growth factor, epidermal growth factor and RET receptor tyrosine kinases. The safety and tolerability of vandetanib plus mFOLFOX6 was investigated in patients with advanced colorectal cancer (CRC).
METHODS
Patients eligible for first- or second-line chemotherapy received once-daily oral doses of vandetanib (100 or 300 mg) plus 14-day treatment cycles of mFOLFOX6.
RESULTS
Seventeen patients received vandetanib 100 mg (n = 9) or 300 mg (n = 8) plus mFOLFOX6. The protocol definition of a tolerable dose (vandetanib-related dose-limiting toxicity [DLT] in less than two patients) was met in both dose cohorts, with one DLT of diarrhoea reported in each. Overall, the most common adverse events were diarrhoea, nausea and lethargy (all n = 11). There was no pharmacokinetic interaction between vandetanib and mFOLFOX6. Preliminary efficacy results included one complete response and three confirmed partial responses.
CONCLUSIONS
In patients with advanced CRC, once-daily vandetanib (100 or 300 mg) with mFOLFOX6 was generally well tolerated.
背景
凡德他尼（ZACTIMA）是一种每日一次口服的血管内皮生长因子、表皮生长因子和RET受体酪氨酸激酶抑制剂。研究了凡德他尼联合mFOLFOX6方案在晚期结直肠癌（CRC）患者中的安全性和耐受性。
方法
符合一线或二线化疗条件的患者接受每日一次口服凡德他尼（100或300毫克）加为期14天的mFOLFOX6治疗周期。
结果
17例患者接受了凡德他尼100毫克（n = 9）或300毫克（n = 8）加mFOLFOX6治疗。两个剂量组均达到了可耐受剂量的方案定义（少于两名患者出现凡德他尼相关剂量限制性毒性[DLT]），每组均报告了1例腹泻DLT。总体而言，最常见的不良事件为腹泻、恶心和乏力（均n = 11）。凡德他尼与mFOLFOX6之间不存在药代动力学相互作用。初步疗效结果包括1例完全缓解和3例确认的部分缓解。
结论
在晚期CRC患者中，每日一次的凡德他尼（100或300毫克）联合mFOLFOX6通常耐受性良好。
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