滋燥养荣颗粒治疗非小细胞肺癌EGFRIs相关皮肤干燥症阴虚血燥证有效性及安全性的长期随访研究

The Effect and Safety of Zizao Yangrong Granules (滋燥养荣颗粒) for EGFRIs-related Skin Xerosis with Yin Deficiency and Blood Dryness Pattern: A Long-term Follow-up Study

目的 评估滋燥养荣颗粒对应用表皮生长因子受体抑制剂(EGFRIs)治疗的非小细胞肺癌患者出现相关皮肤干燥症的长期疗效及安全性。方法 基于前期临床试验研究对象,即非小细胞肺癌EGFRIs相关皮肤干燥症阴虚血燥证患者66例,其中治疗组与对照组各33例。对照组患者予维生素E乳外用联合安慰剂口服,治疗组患者给予维生素E乳外用联合滋燥养荣颗粒口服,两组均每日1剂,疗程为4周以上。本研究每3个月对患者进行电话随访,记录两组患者无进展生存期(PFS)。对治疗组口服滋燥养荣颗粒8周以上的患者进行问卷随访调查,分析长期服用滋燥养荣颗粒的症状疗效及安全性,采用皮肤生活质量量表(DLQI)评价生活质量。结果 成功随访54例患者,其中试验组30例,对照组24例。试验组患者中位PFS为41.6(0.60,1.75)个月,对照组为40.9 (0.57,1.67)个月,两组差异无统计学意义(HR=0.85,95%CI:0.48~1.51,P=0.586)。治疗组共有19例患者服用滋燥养荣颗粒超过8周,至随访截点19例患者中皮肤干燥总有效率84.2%(16/19),全身干燥总有效率89.5%(17/19),瘙痒总有效率72.2%(13/18)。随访截点时19例患者生活质量量表(DLQI)评分中位数为6 (5,8)分,相较于用药前中位数4 (2,5)分明显升高(P<0.01)。19例患者中发生不良反应11例,分析原因其中6例与滋燥养荣颗粒治疗无关,无3级以上治疗相关不良事件发生。结论 非小细胞肺癌EGFRIs相关皮肤干燥症阴虚血燥证患者使用滋燥养荣颗粒不会影响其PFS,长期口服可缓解EGFRIs所致皮肤干燥、瘙痒症状,提高患者生活质量,且安全性良好。

Objective To explore the long-term effect and safety of Zizao Yangrong Granules(ZYG,滋燥养荣颗粒)for skin xerosis in non-small cell lung cancer patients with previous treatment of epidermal growth factor receptor inhibitors(EGFRIs).Methods Sixty-six non-small cell lung cancer patients patients with EGFRIs-related skin xerosis in a previous trial were retrospectively included,with 33 patients each in the treatment and control group.Besides the external use of vitamin E emulsion,patients in the treatment group received oral ZYG,while those in the control group were given placebo of ZYG,one dose daily for at least four weeks.The patients were followed up by telephone every 3 months,and the progression-free survival(PFS)of the two groups were recorded.A follow-up questionnaire was conducted among patients who took ZYG for more than 8 weeks,and the clinical effect and safety of long-term ZYG were evaluated.The dermatology life quality index(DLQI)was used to assess the quality of life.Results Fifty-four patients were successfully followed,with 30 cases in the treatment group and 24 cases in the control group.Median PFS in the treatment group was 41.6(0.60,1.75)months,and that in control group was 40.9(0.57,1.67)months,with no statistical difference between groups(HR=0.85,95%CI 0.48 to 1.51,P=0.586).A total of 19 patients took ZYG for more than 8 weeks in the treatment group.The overall effective rate was 84.2%(16/19)in relieving skin xerosis,89.5%(17/19)in relieving body xerosis,and 72.2%(13/18)in relieving pruritus,respectively.Besides,the median DLQI score of the 19 patients was 6(5,8),significantly higher than 4(2,5)before treatment(P<0.001).Among the 19 patients,there were 11 cases of adverse reactions,and 6 cases were not related to the treatment of ZYG.And there were no treatment-related adverse events of grade 3 or above.Conclusions ZYG could not affect PFS of non-small cell lung cancer patients with EGFRIs-related skin xerosis of yin deficiency and blood dryness pattern,but long-term oral administration can relieve the dry skin and itching symptoms induced by EGFRIs and improve the quality of life,and is of good safety.