Safety and activity of temsirolimus and bevacizumab in patients with advanced renal cell carcinoma previously treated with tyrosine kinase inhibitors: a phase 2 consortium study.
Safety and activity of temsirolimus and bevacizumab in patients with advanced renal cell carcinoma previously treated with tyrosine kinase inhibitors: a phase 2 consortium study.
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替西罗莫司和贝伐单抗在先前接受酪氨酸激酶抑制剂治疗的晚期肾细胞癌患者中的安全性和活性：一项 2 期联合研究。
DOI：
10.1007/s00280-014-2668-5
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发表时间：
2015
影响因子：
3
通讯作者：
Erlichman,Charles
中科院分区：
文献类型：
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作者：
Merchan,JaimeR;Qin,Rui;Pitot,Henry;Picus,Joel;Liu,Glenn;Fitch,Tom;Maples,WilliamJ;Flynn,PatrickJ;Fruth,BriantF;Erlichman,Charles
目的贝伐单抗或替西罗莫司方案一线治疗晚期肾细胞癌（RCC）具有临床疗效。进行I/II期试验以确定联合两种药物的安全性及其在至少一种先前抗VEGF受体酪氨酸激酶抑制剂（RTKI）药物进展的RCC患者中的疗效。（每周25 mg IV）和每隔一周IV贝伐珠单抗递增剂量（水平1 = 5 mg/kg;水平2 = 10 mg/kg）。II期部分（RTKI耐药患者）的主要终点是6个月无进展率。次要终点反应率，毒性评价，PFS和OS.ResultsMaximum耐受剂量没有达到在12个I期患者的最大剂量。40例可评价患者接受II期推荐剂量（替西罗莫司25 mg IV每周一次和贝伐珠单抗10 mg/kg IV每2周一次）治疗。6个月无进展率为40%（16/40例患者）。中位PFS为5.9（4-7.8）个月，中位OS为20.6（11.5-23.7）个月。部分缓解、疾病稳定和疾病进展分别见于23%、63%和14%的患者。最常见的3-4级AE包括疲乏（17.8%）、高血糖（11.1%）、口腔炎（8.9%）、蛋白尿（8.9%）、腹痛（6.7%）和贫血（6.7%）。血清sFLT-1和VEGF-A的基线水平呈负相关，PFS和OS，respectively.ConclusionsTemsirolimus和贝伐单抗是一个可行的组合在晚期肾癌患者以前暴露于口服抗VEGF药物。安全性和有效性结果需要在该患者人群中进行进一步的确证性研究。
PurposeBevacizumab or temsirolimus regimens have clinical activity in the first-line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent.MethodsIn the phase I portion, eligible patients were treated with temsirolimus (25 mg IV weekly) and escalating doses of IV bevacizumab (level 1 = 5 mg/kg; level 2 = 10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression-free rate. Secondary endpoints were response rate, toxicity evaluation, and PFS and OS.ResultsMaximum tolerated dose was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (temsirolimus 25 mg IV weekly and bevacizumab 10 mg/kg IV every 2 weeks). The 6-month progression-free rate was 40 % (16/40 pts). Median PFS was 5.9 (4–7.8) months, and median OS was 20.6 (11.5–23.7) months. Partial response, stable disease, and progressive disease were seen in 23, 63, and 14 % of patients, respectively. Most common grade 3–4 AEs included fatigue (17.8 %), hypertriglyceridemia (11.1 %), stomatitis (8.9 %), proteinuria (8.9 %), abdominal pain (6.7 %), and anemia (6.7 %). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively.ConclusionsTemsirolimus and bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population.