舒尼替尼相关性血液学不良反应与晚期肾癌预后的相关性分析

Correlation between sunitinib-induced hematological toxicities and prognosis in advanced renal cancer patients

目的：探讨舒尼替尼相关性血液学不良反应与晚期肾细胞癌的预后关系。方法：选取2010年6月-2014年6月上海长征医院泌尿外科收治的56例晚期肾癌患者,29例行肾脏原发病灶切除术,病理诊断为肾透明细胞癌。治疗方案：舒尼替尼50mg,1次/d,采用4/2方案,即每治疗4周停2周为1个周期;每治疗1个周期或2个周期通过CT或MRI评价药物疗效。每周期血常规、肝肾功能检查评价不良反应。结果：中性粒细胞减少组,完全缓解（CR）2例（5.5%）,部分缓解（PR）9例（25.0%）,疾病稳定（SD）11例（30.6%）,ORR为30.6%（8例）;中性粒细胞正常组,CR 1例（5.0%）,PR 2例（10.0%）,SD 8例（40.0%）,ORR为15.0%（3例）。中性粒细胞减少组患者的ORR高于中性粒细胞正常组患者的ORR,但差异无统计学意义。中性粒细胞减少组无进展生存期（12.2个月,95%CI：10.8-13.6）较正常组（8.7个月,95%CI：6.9-10.4）显著延长（P=0.007）。血小板下降组相较血小板正常组患者中位疾病无进展时间明显延长（P=0.011）,中性粒细胞/淋巴细胞比率（〈2）较中性粒细胞/淋巴细胞比率（≥2）的患者中位疾病无进展时间明显延长（P=0.008）。结论：在舒尼替尼治疗中出现一些血液学不良反应的晚期肾细胞癌患者的中位无疾病进展时间更长,这些血液学不良反应可以作为预测药物疗效的有效指标。

Objective：To evaluate correlation between sunitinib-induced hematological toxicities and prognosis in patients with advanced renal cell carcinoma.Method：Fifty-six patients with advanced renal cell carcinoma were enrolled from June 2010 to June 2014,including 38 males and 18 females with median age 53.5（range,40-78）years old.Twenty-nine patients received prior radical nephrectomy and were diagnosed as renal clear cell carcinoma in pathology.Sunitinib was started at a dose of 50mg/d orally on a four-week-on and two-week-off schedule.Treatment was given in six-week cycles until disease progression,lack of clinical benefit or unacceptable toxicity.CT or MRI scan were used to evaluate sunitinib efficacy every two cycles.Hematological toxicities were recorded regularly and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events（CTCAE）based on absolute neutrophil and platelet counts every cycle.Result：Neutropenia group had complete response（CR）2（5.5%）,partial response（PR）9（25.0%）,stable disease（SD）11（30.6%）and objective response rate（ORR）30.6%.Correspondingly,normal neutrophil group patients indicated CR 1（5.0%）,PR 2（10.0%）,SD 8（40.0%）and ORR 15.0%.The ORR of neutropenia group patients was higher than that of normal neutrophil group,but there was no significant difference between two groups.Notably,neutropenia group was significantly associated with longer median progression-free survival（PFS）compared to normal neutrophil group（12.2months,95%CI：10.8-13.6vs.8.7months,95%CI：6.9-10.4,P =0.007）.Besides,thrombocytopenia and ratio of neutrophil/lymphocytes（NLR2）were both correlated with longer median PFS compared to normal control group（P =0.011 and P =0.008,respectively）.Conclusion：Sunitinib-induced hematological toxicities indicate longer median PFS in advanced renal cell carcinoma,which may be exploited as predictive factors for assessment of sunitinib efficacy.