Neoadjuvant Clinical Trial With Sorafenib for Patients With Stage II or Higher Renal Cell Carcinoma
Neoadjuvant Clinical Trial With Sorafenib for Patients With Stage II or Higher Renal Cell Carcinoma
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DOI：
10.1200/jco.2009.24.7759
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发表时间：
2010-03-20
影响因子：
45.3
通讯作者：
Rathmell, W. Kimryn
中科院分区：
文献类型：
--
作者：
Cowey, C. Lance;Amin, Chirag;Rathmell, W. Kimryn
目的应用多靶点酪氨酸激酶抑制剂索拉非尼治疗晚期肾细胞癌。然而，该药物在术前的安全性和有效性还有待评估，在术前可能有潜在的优势，包括肿瘤分期降低。这项前瞻性试验评估了索拉非尼在术前的安全性和可行性。患者和方法30例临床II期及以上肾肿块患者，根据其是否适合行肾切除术，接受索拉非尼术前治疗。监测毒性、手术并发症和肿瘤反应。结果入选的30例患者中，17例有局限性疾病，13例有转移性疾病。经过一个疗程的索拉非尼治疗（中位持续时间，33天），还观察到原发肿瘤大小的减少（中位，9.6%）和肿瘤内强化消失的影像学证据，使用与Choi标准相似的方法进行量化（中位，13%）。根据实体瘤应答评价标准，28例可评价应答的患者中，2例部分应答，26例病情稳定，治疗无进展。索拉非尼的毒性与这类药物的预期相似。所有患者都能进行肾切除术，没有观察到与索拉非尼给药相关的手术并发症。结论术前给予索拉非尼治疗可以影响原发肿瘤的大小和密度，是安全可行的。需要进一步的研究来确定术前全身治疗是否能改善肾细胞癌患者行肾切除术的预后。
PurposeThe multitargeted tyrosine kinase inhibitor sorafenib is used for the treatment of advanced-stage renal cell carcinoma. However, the safety and efficacy of this agent have yet to be evaluated in the preoperative period, where there may be potential advantages including tumor downstaging. This prospective trial evaluates the safety and feasibility of sorafenib in the preoperative setting.Patients and MethodsThirty patients with clinical stage II or higher renal masses, selected based on their candidacy for nephrectomy, underwent preoperative treatment with sorafenib. Toxicities, surgical complications, and tumor responses were monitored.ResultsOf the thirty patients enrolled, 17 patients had localized disease and 13 had metastatic disease. After a course of sorafenib therapy (median duration, 33 days), a decrease in primary tumor size (median, 9.6%) and radiographic evidence of loss of intratumoral enhancement, quantified using a methodology similar to Choi criteria (median, 13%), was also observed. According to Response Evaluation Criteria in Solid Tumors, of the 28 patients evaluable for response, two patients had a partial response and 26 had stable disease, with no patients progressing on therapy. Toxicities from sorafenib were similar to that expected with this class of medication. All patients were able to proceed with nephrectomy and no surgical complications related to sorafenib administration were observed.ConclusionThe administration of preoperative sorafenib therapy can impact the size and density of the primary tumor and appears safe and feasible. Further studies are required to determine if preoperative systemic therapy improves outcomes in patients undergoing nephrectomy for renal cell carcinoma.