Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan.
Department of Gastroenterological Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan.
Onco Targets Ther. 2014 Feb 15;7:289-95. doi: 10.2147/OTT.S58089. eCollection 2014.
Renal cell carcinoma (RCC) with sarcomatoid differentiation is invasive, refractory to treatment, and has a higher mortality. Therefore, systemic therapy is still challenging, and the curative resection of localized or locally advanced RCC with sarcomatoid differentiation is very important. Axitinib is a potent and selective second-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor with improved safety and tolerability. Axitinib is generally recommended as second-line therapy for advanced RCC because the phase III axitinib versus sorafenib in advanced RCC (AXIS) trial demonstrated that it achieved longer progression-free survival than sorafenib in patients with metastatic RCC after failure of an approved first-line regimen.
We present a 73-year-old man who had a large (13 cm in diameter) right RCC with sarcomatoid differentiation that directly invaded the duodenum and inferior vena cava. The patient presented with gastrointestinal bleeding, was unable to eat solid food, and had become emaciated. Thus, his classification was poor risk with anemia, hypercalcemia, and poor performance status, according to the Memorial Sloan-Kettering Cancer Center criteria. He seemed unlikely to survive if radical nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed. To reduce the tumor burden and potential operative complications, we administered axitinib as first-line neoadjuvant therapy.
Six weeks of treatment reduced the tumor burden without causing severe toxicities. Subsequently, radical right nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed successfully. The pathological treatment effect of axitinib was grade 2 (two-thirds necrosis). The resected tumor showed a heterogeneous reaction for phosphorylated Akt (Ser-473) by Western blotting and immunohistochemistry, indicating that parts of the tumor were sensitive to axitinib and other parts were not.
Axitinib might be promising as preoperative or neoadjuvant therapy for locally advanced RCC (>cT3b or >cTanyN1).
具有肉瘤样分化的肾细胞癌（RCC）具有侵袭性、对治疗有抗性且死亡率较高。因此，全身治疗仍然具有挑战性，对于局部或局部晚期具有肉瘤样分化的 RCC 的治愈性切除非常重要。阿昔替尼是一种有效的、选择性的第二代血管内皮生长因子受体酪氨酸激酶抑制剂，具有更好的安全性和耐受性。阿昔替尼通常被推荐作为晚期 RCC 的二线治疗药物，因为 III 期阿昔替尼与索拉非尼治疗晚期 RCC（AXIS）试验表明，在接受批准的一线治疗方案失败后，转移性 RCC 患者的无进展生存期比索拉非尼更长。
我们报告了一位 73 岁男性患者，其右侧 RCC 直径为 13cm，具有肉瘤样分化，直接侵犯十二指肠和下腔静脉。患者出现胃肠道出血，无法进食固体食物，身体消瘦。因此，根据 Memorial Sloan-Kettering Cancer Center 标准，他的分类为贫血、高钙血症和一般状况较差的高危人群。如果进行根治性肾切除术、腔静脉切开取栓术和胰十二指肠切除术，他可能无法存活。为了降低肿瘤负担和潜在的手术并发症，我们给予阿昔替尼作为一线新辅助治疗。
6 周的治疗使肿瘤负担减轻，且未引起严重的毒性反应。随后，成功进行了根治性右肾切除术、腔静脉切开取栓术和胰十二指肠切除术。阿昔替尼的病理治疗效果为 2 级（三分之二坏死）。切除的肿瘤通过 Western blot 和免疫组化显示出对磷酸化 Akt（Ser-473）的异质性反应，表明肿瘤的部分部位对阿昔替尼敏感，而其他部位则不敏感。
阿昔替尼可能是局部晚期 RCC（>cT3b 或 >cTanyN1）的术前或新辅助治疗的有前途的选择。
