Négrier Sylvie, Moriceau Guillaume, Attignon Valéry, Haddad Véronique, Pissaloux Daniel, Guerin Nicole, Carrie Christian
Univ Lyon, Université Claude Bernard Lyon 1, Lyon, France.
Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
J Med Case Rep. 2018 Nov 25;12(1):351. doi: 10.1186/s13256-018-1875-9.
Renal cell carcinoma represents 3-5% of adult malignant tumors. Metastases are found in 30-40% of patients and brain metastases occurred in more than 10% of them. Despite significant progress in medical treatment, patients with brain metastases still have a limited survival. Cabozantinib, a tyrosine kinase inhibitor directed against vascular endothelial growth factor receptors, was recently registered for the treatment of metastatic renal cell carcinoma. Almost no data are, however, available on patients with brain metastases.
Case 1 is a 51-year-old man of North African origin; Case 2 is a 55-year-old European man. Case 1 and Case 2 had metastases of renal carcinoma at initial diagnosis and were treated with vascular endothelial growth factor receptors tyrosine kinase inhibitors. Case 1 had clear cell renal carcinoma and underwent nephrectomy; he then received several lines of tyrosine kinase inhibitor directed against vascular endothelial growth factor receptors and the mTor complex. During the second treatment a brain metastasis was diagnosed and treated with radiosurgery with rapid efficacy. Two years later he received nivolumab, an antibody directed against the programmed death-1 and programmed death-ligand 1 complex, but disease progression was observed with the reappearance of the brain metastasis together with neurologic symptoms. Cabozantinib was administered and induced a rapid clinical improvement as well as tumor regression in all sites including his brain. Sequencing of his tumor evidenced a mutation of the MET gene. Case 2 had a papillary renal carcinoma with brain metastases at time of diagnosis. After radiation of the brain tumors, a vascular endothelial growth factor receptor tyrosine kinase inhibitor was administered for 3 years. The disease was under control in all sites except in his brain; several new brain metastases requiring new radiation treatments developed. The disease finally progressed at all metastatic sites including his brain and he had several neurological symptoms. Cabozantinib was administered and rapidly induced a clinical improvement; a further computed tomography scan and brain magnetic resonance imaging showed significant tumor regressions. No MET gene mutation or amplification was observed in the tumor analysis.
These case reports indicate that cabozantinib was able, first, to reach brain tumors and second, to induce significant regressions in renal carcinoma brain metastases that were resistant to radiation as well as to previous systemic vascular endothelial growth factor receptor tyrosine kinase inhibitors.
肾细胞癌占成人恶性肿瘤的3% - 5%。30% - 40%的患者会发生转移，其中超过10%会出现脑转移。尽管在医学治疗方面取得了显著进展，但脑转移患者的生存期仍然有限。卡博替尼是一种针对血管内皮生长因子受体的酪氨酸激酶抑制剂，最近已获批用于治疗转移性肾细胞癌。然而，关于脑转移患者的数据几乎没有。
病例1是一名51岁的北非男性；病例2是一名55岁的欧洲男性。病例1和病例2在初诊时就有肾癌转移，并接受了血管内皮生长因子受体酪氨酸激酶抑制剂治疗。病例1患有透明细胞肾细胞癌，接受了肾切除术；随后他接受了几线针对血管内皮生长因子受体和mTor复合物的酪氨酸激酶抑制剂治疗。在第二次治疗期间，诊断出脑转移并接受了放射外科治疗，疗效迅速。两年后，他接受了纳武单抗治疗，这是一种针对程序性死亡受体1和程序性死亡配体1复合物的抗体，但观察到疾病进展，脑转移复发并伴有神经症状。给予卡博替尼后，临床症状迅速改善，包括脑部在内的所有部位肿瘤均消退。对其肿瘤进行测序发现MET基因突变。病例2在诊断时患有乳头状肾细胞癌并伴有脑转移。在对脑肿瘤进行放疗后，给予血管内皮生长因子受体酪氨酸激酶抑制剂治疗3年。除脑部外，所有部位的疾病均得到控制；出现了几个新的脑转移灶，需要再次进行放射治疗。疾病最终在包括脑部在内的所有转移部位进展，他出现了多种神经症状。给予卡博替尼后，临床症状迅速改善；进一步的计算机断层扫描和脑磁共振成像显示肿瘤明显消退。在肿瘤分析中未观察到MET基因突变或扩增。
这些病例报告表明，卡博替尼首先能够到达脑肿瘤，其次能够使对放疗以及先前的全身血管内皮生长因子受体酪氨酸激酶抑制剂耐药的肾癌脑转移灶显著消退。
