低剂量奥拉帕利联合贝伐珠单抗对老年复发性铂敏感型卵巢癌患者的疗效和安全性研究

Efficacy and safety of low-dose olaparib combined with bevacizumab in elderly patients with recurrent platinum-sensitive ovarian cancer

摘要:

目的 探讨低剂量奥拉帕利联合贝伐珠单抗对老年复发性铂敏感型卵巢癌患者的疗效和安全性。方法 选取2021年1月—2023年1月南阳市第一人民医院收治的102例复发性铂敏感型卵巢癌老年患者，并按随机数字表法分为对照组、低剂量组和高剂量组，各34例。患者均接受贝伐珠单抗维持治疗，低剂量组在此基础上联合口服奥拉帕利150 mg/次、2次/d，高剂量组联合口服奥拉帕利300 mg/次、2次/d。4周/疗程，维持治疗6个疗程。比较两组的临床疗效，以及治疗前后的肿瘤标志物水平［人附睾上皮分泌蛋白4（HE4）、糖类抗原125（CA125）、CA199］和免疫功能（CD3^＋、CD4^＋、CD8^＋），并通过生活质量问卷（QLQ-C30）评估患者治疗前后的生活质量，记录不良反应情况。结果 低剂量组、高剂量组客观缓解率均高于对照组（P <0.05）。高剂量组治疗后HE4、CA125、CA199水平均低于低剂量组、对照组（P <0.05）。治疗后各组HE4、CA125、CA199均较治疗前降低（P <0.05）。高剂量组治疗前后HE4、CA125、CA199水平的差值均大于低剂量组和对照组（P <0.05）。低剂量组治疗后的CD3⁺、CD4⁺水平高于高剂量组和对照组（P <0.05），CD8⁺水平低于高剂量组和对照组（P <0.05）。治疗后各组CD3⁺、CD4⁺水平均较治疗前降低（P <0.05），CD8⁺水平升高（P <0.05）。低剂量组治疗前后CD3⁺、CD4⁺、CD8⁺水平的差值均小于高剂量组和对照组（P <0.05）。低剂量组治疗后运动、健康状态、活动、生活行为评分高于高剂量组和对照组（P <0.05）。治疗后各组运动、健康状态、活动、生活行为评分均较治疗前升高（P <0.05）。低剂量组治疗前后运动、健康状态、活动、生活行为评分的差值均大于高剂量组和对照组（P <0.05）。结论 低剂量奥拉帕利联合贝伐珠单抗与高剂量方案疗效相当，且在免疫功能、生活质量改善及安全性方面更具优势。

Abstract:

Objective To investigate the efficacy and safety of low-dose olaparib combined with bevacizumab in elderly patients with recurrent platinum-sensitive ovarian cancer.Methods A total of 102 elderly patients with recurrent platinum-sensitive ovarian cancer admitted to our hospital from January 2021 to January 2023 were selected and divided into 3 groups using the random number table method, with 34 cases in each of the control group, low-dose group and high-dose group. All patients in the three groups received bevacizumab maintenance therapy. On this basis, patients in the low-dose group received oral olaparib at 150 mg twice daily, whereas those in the high-dose group received oral olaparib at 300 mg twice daily. Treatment was administered in 4-week cycles for a total of six maintenance cycles. Clinical efficacy was compared between the two groups, along with changes in tumor marker levels and immune function indices (CD3⁺, CD4⁺, and CD8⁺) before and after treatment. Quality of life was evaluated using the QLQ-C30 questionnaire before and after treatment, and adverse events were recorded.Results The objective response rate (ORR) in both the low-dose and high-dose groups was higher than that in the control group (P < 0.05). After treatment, serum levels of HE4, CA125, and CA199 in the high-dose group were lower than those in the low-dose and control groups (P < 0.05). In all groups, HE4, CA125, and CA199 levels decreased significantly compared with baseline (P < 0.05). Moreover, the reductions in HE4, CA125, and CA199 levels were greater in the high-dose group than in the low-dose and control groups (P < 0.05). Post-treatment CD3⁺ and CD4⁺ levels in the low-dose group were higher than those in the high-dose and control groups (P < 0.05), whereas CD8⁺ levels were lower (P < 0.05). After treatment, CD3⁺ and CD4⁺ levels decreased and CD8⁺ levels increased in all groups compared with baseline (P < 0.05). The magnitude of change in CD3⁺, CD4⁺, and CD8⁺ levels was smaller in the low-dose group than in the high-dose and control groups (P < 0.05). Following treatment, scores for physical functioning, global health status, activity, and daily living behavior in the low-dose group were higher than those in the high-dose and control groups (P < 0.05). All groups showed significant improvements in these scores compared with baseline (P < 0.05). Furthermore, the increases in these scores were greater in the low-dose group than in the high-dose and control groups (P < 0.05).Conclusion Low-dose olaparib combined with bevacizumab exhibits comparable efficacy to the high-dose regimen in elderly patients with recurrent platinum-sensitive ovarian cancer, and is superior in improving immune function and quality of life while maintaining a favorable safety profile.