吉西他滨联合顺铂/卡铂方案辅助化疗治疗上尿路尿路上皮癌的安全性研究

Safety of gemcitabine combined with platinum-based adjuvant chemotherapy for upper urinary tract urothelial carcinoma

目的探讨吉西他滨联合顺铂(GC)/卡铂(GCa)方案辅助化疗治疗上尿路尿路上皮癌患者的安全性。方法回顾性分析2012年6月—2018年1月首都医科大学附属北京友谊医院收治的80例上尿路尿路上皮癌(UTUC)术后行4周期内GC或GCa方案化疗的患者的临床和随访资料。。其中男性39例,女性41例,中位年龄64.0岁,年龄范围36~81岁。按照化疗方案分为GC组(n=54)和GCa组(n=26)。采用SPSS25.0软件统计两组患者化疗不良反应发生率,总结化疗不良反应情况;分析发生严重不良反应的独立危险因素;探究肾功能不全患者严重不良反应发生率和化疗期间肾功能安全性情况。结果化疗不良反应:GC组出现严重骨髓抑制20例(37.0%),出现严重非血液学毒性有9例(16.4%),因严重化疗不良反应而延迟化疗3例(5.6%),因不能耐受化疗毒性反应提前退出化疗12例(22.2%)。GCa组出现严重骨髓抑制有12例(46.2%),出现严重非血液学毒性有5例(19.2%),因严重化疗不良反应而延迟化疗6例(23.1%),因不能耐受化疗毒性反应提前退出化疗6例(23.1%)。化疗前估算肾小球滤过率eGFR<60 ml·(min·1.73 m2)-1(OR=5.074,95%CI: 1.222~21.068)是GC组发生严重骨髓抑制的独立危险因素(P<0.05)。两组在严重不良反应方面差异无统计学意义(P<0.05)。两组肾功能不全患者化疗期间肌酐和eGFR有一定程度降低(P<0.05),但肾功能下降的数值和程度差异均无统计学意义(P<0.05)。结论GC和GCa方案均存在一定的化疗不良反应,化疗过程需严密监测,及时对症处理,多数患者可最终耐受化疗;对肾功能不全的患者,在严密监测和充分水化的前提下,4周期内GC和GCa方案可能是同等安全水平的化疗方案。

Objective To investigate the safety of gemcitabine combined with cisplatin (GC)/ carboplatin (GCa) regimen in adjuvant chemotherapy for upper urinary tract urothelial carcinoma. Methods The clinical and follow-up data of 80 patientswho underwent GC or GCa chemotherapy withinfourcycles of upper tract urothelial carcinoma (UTUC) admitted to Beijing Friendship Hospital, Capital Medical University from June 2012 to January 2018 were analyzed retrospectively, including 39 males and 41 females, aged 36 to 81 years, with a median age of 64.0 years. According to the chemotherapy regimen, all patients were divided into GC group (n=54) and GCa group (n=26). The software of SPSS 22.0 was used to calculate the incidence of adverse reactions of chemotherapy. The independent risk factors for serious adverse reactions were analyzed. The incidence of serious adverse reactions and the safety of renal function in patients with renal insufficiency during chemotherapy were explored. Results For adverse reactions to chemotherapy, GC group had 20 patients(37.0%) with severe myelosuppression, 9 patients(16.4%) with non-hematological toxicity, 3 patients (5.6%) with delayed chemotherapy due to serious chemotherapy adverse reactions, and 12 patients (22.2%) withdrawn chemotherapy early due to inability to tolerate chemotherapy toxicity. In GCa group, 12 patients(46.2%) had severe myelosuppression, 5 patients(19.2%) had severe non-hematologic toxicity, 6 patients(23.1%) had delayed chemotherapy due to serious chemotherapy adverse reactions, and 6 patients (23.1%) had withdrawn chemotherapy early due to inability to tolerate chemotherapy toxicity. Pre-chemotherapye GFR<60 ml·(min·1.73 m2)-1(OR=5.074, 95%CI: 1.222-21.068) was an independent risk factor for severe myelosuppression in GC group (P<0.05). There was no significant difference in severe adverse reactions between the two groups (P<0.05). For the renal function decline between the two groups, Cr and eGFR decreased to a certain extent in the two groups during chemotherapy (P<0.05), but there was no significant difference in the extent and degree during chemotherapy (P<0.05). Conclusions Both GC and GCa adjuvant chemotherapy have certain toxicity and side effects. The process of chemotherapy needs to be closely monitored and timely symptomatic treatment if needed. Most patients can eventually endure chemotherapy.For patients with renal insufficiency, under the precondition of strict monitoring and adequate hydration, GC and GCa regimens adjuvant chemotherapy within four cycles may be the same safe level ofchemotherapy.