吉西他滨联合奥沙利铂方案在顺铂不耐受尿路上皮癌患者术后辅助治疗中的疗效和安全性

Efficacy and safety of gemcitabine combined with oxaliplatin chemotherapy regimen in cisplatinintolerant uroepithelial carcinoma

目的评估吉西他滨联合奥沙利铂(GEMOX)方案在顺铂不耐受尿路上皮癌患者术后辅助治疗中的疗效和安全性。方法回顾性分析2017年8月至2022年10月于南京大学医学院附属鼓楼医院接受根治手术后不耐受顺铂化疗的98例尿路上皮癌患者的临床资料。根据患者术后是否行辅助化疗分为辅助化疗组和观察组,辅助化疗组术后接受GEMOX方案化疗(吉西他滨1000 mg/m^(2)静脉滴注,第1、8天;奥沙利铂130mg/m^(2)静脉滴注,第2天;每3周为1个周期);观察组术后未进行辅助化疗,术后常规行影像学观察。辅助化疗组43例,男33例,女10例;年龄(67.8±7.3)岁;33例估算肾小球滤过率(eCFR)≤60ml/(min·1.73m^(2)),10例美国东部肿瘤协作组(ECOG)评分>1分;术后病理T_(3)期39例,T_(4)期4例;淋巴结阳性(N+)10例。观察组55例,男42例,女13例;年龄(70.7±7.7)岁;其中42例eCFR≤60ml/(min·1.73m^(2)),13例ECOG评分>1分;48例患者术后病理T_(3)期48例,T_(4)期7例;N+13例。观察辅助化疗组肾功能及ECOG评分的变化和不良反应。采用Kaplan-Meier法估算生存率,组间生存率的比较采用log-rank检验。多因素Cox回归分析年龄、淋巴结、是否联合辅助化疗等与患者生存的相关情况。结果本研究所有患者随访3~75个月,中位随访时间22(14,34)个月,观察组和辅助化疗组复发率分别为83.6%(46/55)和65.1%(28/43),病死率分别为52.7%(29/55)和27.9%(12/43)。Kaplan-Meier生存分析结果显示,辅助化疗组1、2、3年无病生存率分别为62.8%、48.6%和41.1%,1、2、3年总生存率分别为86.0%、79.0%和76.4%;观察组1、2、3年无病生存率分别为58.2%、22.6%和9.6%,1、2、3年总生存率分别为78.2%、49.4%和42.8%,辅助化疗组较观察组的无病生存率和总生存率均有优势(P<0.05)。多因素Cox回归分析结果提示ECOG评分及是否伴淋巴结阳性、糖尿病、联合辅助化疗是影响患者生存的独立危险因素(P<0.05)。43例辅助化疗1~6个疗程,中位值为4(2,4)个疗程。安全性方面,胃肠道最常见的不良反应是食欲减退(53.4%,23/43);血液系统最常见的1~2级不良反应为血红蛋白下降(51.2%,22/43),最常见的3~4级不良反应为血小板减少(9.3%,4/43)。辅助化疗组33例肾功能不全的患者在各用药周期后的eGFR均高于用药前(P<0.05),且肾功能并未随着用药周期增加而恶化。10例ECOG评分为2分的患者化疗后评分仍为2分。结论在顺铂不耐受的尿路上皮癌患者中,GEMOX方案可提高患者的总生存率,同时其耐受性良好且未增加肾毒性,是顺铂不耐受的尿路上皮癌患者可选择的术后辅助治疗方式。

Objective To evaluate the efficacy and safety of the gemcitabine combined with oxaliplatin(GEMOX)regimen in the postoperative adjuvant treatment for the patients with cisplatinintolerant uroepithelial cancer.Methods The clinical data of 98 patients with uroepithelial carcinoma intolerant to cisplatin chemotherapy who underwent radical surgery from August 2017 to October 2022 at Drum Tower Hospital of Nanjing University School of Medicine were retrospectively analysed.The patients were divided into the adjuvant chemotherapy group and the observation group according to whether or not they underwent adjuvant chemotherapy after surgery.The adjuvant chemotherapy group received postoperative chemotherapy with the CEMOX regimen(gemcitabine 1000 mg/m^(2)intravenously on days 1 and 8,oxaliplatin 130 mg/m^(2)intravenously on day 2,every 3 weeks as a cycle),and the observation group did not undergo postoperative adjuvant chemotherapy.In the adjuvant chemotherapy group,there were 33 males and 10 females,the patients'age was(67.8±7.3)years old,33 cases with estimated glomerular filtration rate(eGFR)≤60 ml/(min·1.73m^(2)),and 10 cases with a Eastern Cooperative Oncology Group(ECOG)functional status score of>1.The postoperative pathology showed 39 cases were in stage T_(3),4 cases in stage T_(4),and lymph node positivity(N+)was found in 10 cases.There were 55 cases in the observation group,with 42 males and 13 females and the age of(70.7±7.7)years old.Forty-two of them had an eGFR≤60 ml/(min·1.73m^(2)),and 13 of them had a ECOG score of>1.The postoperative pathology showed 48 cases were in stage T_(3),7 cases in stage T_(4),and 13 cases of N+.The changes in renal function,ECOG scores,and adverse reactions were observed in adjuvant chemotherapy group.Kaplan-Meier method was used to estimate the survival rate,and the log-rank test was used to compare the survival rate between groups.Multifactorial Cox regression was used to analyse the correlation between age,lymph nodes,whether or not to combine with adjuvant chemotherapy and the survival of patients.Results All patients in this study were followed up for 3 to 75 months,with a median follow-up time of 22(14,34)months.The recurrence rates were 83.6%(46/55)and 65.1%(28/43)in the observation and adjuvant chemotherapy groups,respectively,and the disease mortality rates were 52.7%(29/55)and 27.9%(12/43),respectively.The results of the Kaplan-Meier survival analyses showed that the 1-,2-and 3-year disease-free survival rates in the adjuvant chemotherapy group were 62.8%,48.6% and 41.1%,respectively,and the 1-,2-and 3-year overall survival rates were 86.0%,79.0%and 76.4%,respectively.The 1-,2-and 3-year disease-free survival rates of the observation group were 58.2%,22.6% and 9.6%,respectively,and the 1-,2-and 3-year overall survival rates were 78.2%,49.4%and 42.8%,respectively.The adjuvant chemotherapy group had an advantage over the observation group regarding disease-free and overall survival rates(all P<0.05).The results of multifactorial Cox regression analysis suggested that the functional status score and the presence or absence of positive lymph nodes,diabetes mellitus,and co-adjuvant chemotherapy were independent risk factors affecting the survival of the patients(P<0.05).Forty-three cases had 1 to 6 courses of adjuvant chemotherapy,with a median course of 4(2,4).In terms of safety,the most common adverse reaction in the gastrointestinal tract was loss of appetite(53.4%,23/43),the most common grade 1 to 2 adverse reaction in myelosuppression was a decrease in haemoglobin(51.2%,22/43),and the most common grade 3 to 4 adverse reaction was thrombocytopenia(9.3%,4/43).The eGFR of 33 patients with renal insufficiency in the adjuvant chemotherapy group was higher after each administration cycle than before(P<0.05),and renal function did not deteriorate with the increase in administration cycles.Ten patients with a ECOG score of 2 remained with a score of 2 after chemotherapy.Conclusions In patients with cisplatin-intolerant uroepithelial cancer,gemcitabine in combination with an oxaliplatin regimen improves the overall survival of patients.At the same time,it is well tolerated without increasing nephrotoxicity,making it an optional postoperative adjuvant treatment for patients with cisplatin-intolerant uroepithelial cancer.