Princess Margaret Hospital, Phase II Consortium, 610 University Avenue, Suite 5-222, Toronto, Ontario M5G 2M9, Canada.
Invest New Drugs. 2011 Oct;29(5):1045-9. doi: 10.1007/s10637-010-9408-4. Epub 2010 Feb 27.
Sorafenib is an oral multikinase inhibitor that blocks cell proliferation via the ERK pathway and angiogenesis via the VEGF pathway. This phase II trial was conducted to determine the efficacy and tolerability of sorafenib for the treatment of patients with metastatic urothelial cancer (UC) who had not had prior chemotherapy for advanced disease.
Seventeen chemo-naïve UC patients with adequate performance status and organ function were treated with sorafenib 400 mg twice daily on a continuous basis until progression or unacceptable toxicity. The primary endpoint was objective tumor response rate as measured by RECIST criteria. Secondary endpoints included rate of prolonged stable disease (>3 months), time to progression, median and 1 yr survival and safety and tolerability.
There were no objective responses. Only one patient had stable disease by RECIST criteria and remained on treatment more than 3 months. Three patients had stable disease by RECIST criteria but were on treatment less than 3 months due to progressive disease (PD) or adverse events (AE). Eight patients had PD by RECIST criteria as their best overall response. Two patients had symptomatic PD prior to cycle 2 evaluation, and three patients were inevaluable (1 death, 1 AE, 1 withdrew consent).The time to progression was 1.9 months (range 0.7-8.7 months) and median survival was 5.9 months. The most common grade 3+ toxicities were abdominal pain, back pain, hand-foot reaction and bladder infection.
Sorafenib does not show sufficient activity as a single agent in first-line metastatic urothelial cancer to warrant further investigation.
索拉非尼是一种口服多激酶抑制剂，通过 ERK 通路阻断细胞增殖，通过 VEGF 通路阻断血管生成。本Ⅱ期试验旨在确定索拉非尼治疗未经化疗的转移性尿路上皮癌（UC）患者的疗效和耐受性，这些患者患有晚期疾病。
17 例化疗初治的 UC 患者，体力状况和器官功能良好，接受索拉非尼 400mg，每日 2 次，连续治疗，直至疾病进展或出现无法耐受的毒性。主要终点是根据 RECIST 标准测量的客观肿瘤缓解率。次要终点包括延长的稳定疾病（>3 个月）率、无进展生存期、中位生存期和 1 年生存率以及安全性和耐受性。
无客观缓解。只有 1 例患者根据 RECIST 标准稳定疾病，且持续治疗超过 3 个月。3 例患者根据 RECIST 标准稳定疾病，但因疾病进展（PD）或不良事件（AE）而治疗时间少于 3 个月。8 例患者根据 RECIST 标准最佳总缓解为 PD。2 例患者在第 2 周期评估前出现症状性 PD，3 例患者无法评估（1 例死亡、1 例 AE、1 例撤回同意）。无进展生存期为 1.9 个月（范围 0.7-8.7 个月），中位生存期为 5.9 个月。最常见的 3+级毒性是腹痛、背痛、手足皮肤反应和膀胱炎。
索拉非尼作为一线转移性尿路上皮癌的单一药物，其活性不足，不值得进一步研究。
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