摘要
目的 探讨奥拉帕利与含铂类药物方案治疗的对铂类药物敏感的BRCA突变卵巢癌复发患者肿瘤特异性生长因子、细胞免疫功能及疗效的差异.方法 回顾性队列研究.回顾性选取2017年9月至2020年3月保定市第二中心医院100例对铂类药物敏感的BRCA突变卵巢癌复发患者,分析患者临床资料.根据治疗方案分为奥拉帕利组(以奥拉帕利片治疗)和含铂方案组(紫杉类药物+铂类药物治疗6个周期后服用奥拉帕利片维持治疗),各50例.比较两组临床疗效及治疗前、治疗2、4、6个周期后肿瘤特异性生长因子[糖类抗原(CA)125、CA199、人附睾蛋白4(HE4)]水平、细胞免疫功能相关指标[T细胞亚群(CD3+细胞、CD4+细胞比例)、CD4+细胞与CD8+细胞比值(CD4+/CD8+)]、生命质量评分及安全性.获得随访3年的数据,采用Kaplan-Meier法分析两组患者无进展生存(PFS)情况,组间比较采用log-rank检验.结果 奥拉帕利组和含铂方案组患者年龄分别为(53±7)岁、(56±7)岁.两组间年龄、体质量指数及美国东部肿瘤协作组(ECOG)体能状态评分、原发肿瘤位置、病灶大小、病理分期、病理类型、胚系BRCA突变、既往化疗反应患者构成差异均无统计学意义(均P＞0.05).治疗结束后,奥拉帕利组客观缓解率(ORR)[58.0％(29/50)比 38.0％(19/50)]、疾病控制率(DCR)[80.0％(40/50)比 56.0％(28/50)]均高于含铂方案组,差异均有统计学意义(均P＜0.05).两组治疗前、治疗2、4、6个周期血清CA125、CA199及HE4水平均逐渐降低(均P＜0.05),且治疗2、4、6个周期后奥拉帕利组这3个指标水平均低于含铂方案组,差异均有统计学意义(均P＜0.05).奥拉帕利组治疗前、治疗2、4、6个周期CD3+细胞比例、CD4+细胞比例及CD4+/CD8+均逐渐升高(均P＜0.05),而含铂方案组均逐渐降低(均P＜0.05);治疗2、4、6个周期后奥拉帕利组这3个指标均高于含铂方案组,差异均有统计学意义(均P＜0.05).两组治疗前、治疗2、4、6个周期后生命质量评分均逐渐升高(均P＜0.05),且治疗2、4、6个周期后奥拉帕利组生命质量评分均高于含铂方案组,差异均有统计学意义(均P＜0.05).奥拉帕利组各级恶心、疲劳和乏力、呕吐、贫血、腹泻发生率均低于含铂方案组,差异均有统计学意义(均P＜0.05).随访3年,奥拉帕利组与含铂方案组PFS差异无统计学意义(P＞0.05).结论 奥拉帕利治疗对铂类药物敏感的BRCA突变卵巢癌复发患者效果优于含铂方案,且其提高患者T细胞水平、抑制肿瘤特异性生长因子表达效果更强,提高生命质量,对提高治疗安全性具有积极作用.
Abstract
Objective To explore the differences in tumor-specific growth factors,cellular immune function and efficacy of olaparib and platinum-containing regimen for treatment of platinum-sensitive relapsed ovarian cancer patients with BRCA mutation.Methods A retrospective cohort study was conducted.A total of 100 platinum-sensitive relapsed BRCA-mutant ovarian cancer patients in Baoding Second Central Hospital from September 2017 to March 2020 were retrospectively selected.The clinical data of the patients were analyzed,and they were divided into the olaparib group(treated with olaparib tablets)and the platinum-containing regimen group(treated with paclitaxel and platinum drugs for 6 cycles,followed by olaparib tablets maintenance therapy),with 50 patients in each group.The clinical efficacy,tumor specific growth factor[carbohydrate antigen(CA)125,CA199,human epididymal protein 4(HE4)]levels,cellular immune function-related indicators[T-cell subsets(proportions of CD3+cells and CD4+cells),CD4+cells/CD8+cells ratio(CD4+/CD8+)],and quality of life scores before treatment and after 2,4 and 6 cycles of treatment of the two groups were compared,as well as the safety of the two groups.The data of three years of follow-up were obtained,Kaplan-Meier method was used to analyze the progression-free survival(PFS)of patients in the two groups,and log-rank test was used for comparison between groups.Results The age of patients in the olaparib and platinum-containing regimen groups was(53±7)years old and(56±7)years old,respectively.The differences in compositions of patients with different age,body mass index,Eastern Cooperative Oncology Group(ECOG)performance status score,primary tumor location,lesion size,pathological stage,pathological type,germline BRCA mutation,and previous chemotherapy response between the two groups were not statistically significant(all P＞0.05).The objective response rate(ORR)[58.0％(29/50)vs.38.0％(19/50)]and disease control rate(DCR)[80.0％(40/50)vs.56.0％(28/50)]of the olaparib group after treatment were higher than those of the platinum-containing regimen group,and the differences were statistically significant(both P＜0.05).Serum CA125,CA199 and HE4 levels were gradually decreased in both groups before treatment and after 2,4 and 6 cycles of treatment(all P＜0.05);serum CA125,CA199 and HE4 levels in the olaparib group after 2,4 and 6 cycles of treatment were lower than those in the platinum-containing regimen group,and the differences were statistically significant(all P＜0.05).The CD3+cells ratio,CD4+cell ratio and CD4+/CD8+in the olaparib group gradually increased before treatment and after 2,4 and 6 cycles of treatment(all P＜0.05),while those in the platinum-containing regimen group all gradually decreased(all P＜0.05);the CD3+cells ratio,CD4+cells ratio and CD4+/CD8+in the olaparib group were higher than those in the platinum-containing regimen group after 2,4 and 6 cycles of treatment,and the differences were statistically significant(all P＜0.05).The quality of life scores of both groups increased before treatment and after 2,4 and 6 cycles of treatment(all P＜0.05),and the quality of life scores of the olaparib group were higher than those of the platinum-containing regimen group after 2,4 and 6 cycles of treatment,and the differences were statistically significant(all P＜0.05).The incidence of nausea,fatigue and malaise,vomiting,anemia,and diarrhea at all levels in the olaparib group was lower than those in the platinum-containing regimen group(all P＜0.05).By follow-up for 3 years,there was no statistically significant difference in PFS between the olaparib group and the platinum-containing regimen group(P＞0.05).Conclusions The efficacy of olaparib treatment in platinum-sensitive relapsed ovarian cancer patients with BRCA mutation is superior to platinum-containing regimen,and it can increase the level of T cells,inhibit the expression of tumor-specific growth factors,improve the quality of life,and have a positive effect on improving the safety of treatment.
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