舒尼替尼治疗晚期肾细胞癌存活期超过3年病例分析:单中心11例报告

Sunitinib for metastatic renal cell carcinoma(mRCC)patients with over three years survival:initial report of 11 cases

目的：回顾性分析11例生存期超过3年的经舒尼替尼治疗的晚期肾癌患者的病史、靶向治疗效果及临床转归特征等，探索与舒尼替尼疗效相关的预测因子。方法：收集存活期超过3年的11例患者的自然信息、疾病特征及接受靶向治疗后的临床疗效及不良反应发生情况，对其rs307826（VEGFR3基因）和rs776746（CYP3A5基因）的单核苷酸多态性（SNP）进行检测，并与国内外文献对照，探讨获得较长生存期的可能因素。结果：11例患者中男10例，女1例，平均年龄57岁。10例接受根治性肾切除术，1例行肾穿刺活检；其中透明细胞癌10例、嫌色细胞癌1例TNM分期T1b8例、T2．3例lFurman分级1级2例、1～2级6例、2级1例、2～3级2例。4例患者在发病时巳出现转移，7例患者在肾根治性切除术后平均31个月出现转移。6例患者为单纯肺转移，3例患者为腹膜后淋巴结转移，甲状腺及皮下转移各1例。舒尼替尼初始给药剂量均为50mg4／2给药方案，平均接受治疗时间41．5个月，中位疾病无进展生存期（PFS）31个月。主要不良反应包括血小板减少症、白细胞减少症、手足皮肤反应及高血压等。rs307826（VEGFR3基因）位点均为A／A型，rs776746（CYP3A5基因）位点G／G型10例，G／A型1例。结论：舒尼替尼治疗晚期肾细胞癌具有良好的有效性和安全性。对于病理分期T1～T2．、Furman分级1～2级、单纯肺转移或淋巴结转移、曾行肾癌根治术及转移发生在肾根治性切除术后较长时间的中青年男性患者，接受舒尼替尼治疗后有望获得更长的存活期。

Objective： A retrospective analysis was made for metastatic renal cell carcinoma （mRCC） patients treated with sunitinib with over three years survival. The history, disease characteristics, efficacy and side effects of targeted therapy and clinical outcomes were studied, and possible predictive factors of response to sunitinib were explored. Method~ Eleven patients had been alive for over three years postoperatively. The history, disease char- acteristics, efficacy and side effects of targeted therapy, clinical outcomes and single nucleotide polymorphism （SNP） were collected. We tried to find the possible predictive factors of response to sunitinib by comparing with the reported in the literature. Result： Ten male and one female patients were analyzed. Average age was 57 years old. Ten eases received radical nephrectomies and one received puncture biopsy. Pathological examination showed clear cell carcinoma in ten eases and chromophobe carcinoma in one ease. Eight eases were Tlb and three were T2x. Two eases were Furman grading 1, and six were grading 1-2. Moreover, Furman grading 2 was found in one case and grading 2-3 were observed in two cases. Metastasis occurred in seven eases at an average of 31 months after radical nephrectomy. Six eases were discovered only pulmonary metastasis and three patients were found retroper- itoneal lymph node metastasis. Thyroid gland metastasis and subcutaneous metastasis were noticed in one case re- spectively. All patients received sunitinib 50rag Qd, 4/2 weeks schedule primarily. Average treatment time was 41.5 months and mPFS was 31 months. The main adverse reactions （AEs） included thrombopenia, leucopenia, hand-foot reaction and hypertension. SNP examination showed that rs307826 （VEGFR3）： A/A was all found in 11 cases! rs776746 （CYP3AS） ~ G/G was shown in ten cases and G/A in one case. Conclusion： The results of this study demonstrate that sunitinib is effective and safe for treatment of mRCC. Middle or young male patients with pathological stage T1-T2,, Furman grading 1-2, pure lung metastasis or lymph node metastasis and metastasis occurring a long interval after nephrectomy, may experience a prolonged survival time under sunitinib treatment.