老年进展期非小细胞肺癌中西医结合个体化治疗方案的临床研究

【作者】 崔芳囡；

【导师】 贾立群；

【作者基本信息】 北京中医药大学 ， 中西医结合临床， 2012， 博士

【摘要】 背景及目的：老年进展期非小细胞肺癌目前尚无标准的化疗方案,MILES研究是至今为止全球最大的一个针对老年进展期非小细胞肺癌的前瞻性、多中心、随机、对照的Ⅲ期临床研究,该研究结果奠定了单药化疗的主导地位,但近年发表的SEER分析显示含铂双药化疗能够使老年患者最终获益。中医研究发现不同肿瘤患者常见某些偏颇的体质,老年肺癌患者最常见的体质为痰瘀体质和气阴两虚体质。中医药在肺癌的治疗中发挥出多样作用。我们根据老年进展期非小细胞肺癌患者的不同体质,给予不同的中西医结合治疗方案,希望能够提高患者的治疗完成率、客观缓解率,改善患者中医症状,提高生存质量,延长疾病无进展生存期和提高1年生存率。我们的目的是以中医体质辩证为基础,探讨老年进展期非小细胞肺癌的中西医结合个体化治疗方案。方法：我们通过前瞻性、开放性、多中心的临床研究原则开展了对进展期老年非小细胞肺癌的临床研究。纳入年龄65岁～80岁的老年进展期(Ⅲb、Ⅳ期)非小细胞肺癌患者,入组开始于2009年9月1日结束于2011年3月15日,随访截止日期为2012年3月15日。所有进入这项研究的患者都必须接受体质评估。气阴两虚体质患者接受单药化疗+益气养阴中药,痰瘀体质患者接受含铂双药化疗+化痰祛瘀中药。在治疗前,和接受第2个周期治疗后对患者进行影像学评价；同时在治疗前和每个治疗周期后对患者中医症状进行评分,并协助患者填写FACT-L4.0生存质量量表,以观察临床症状改善情况和患者的生存质量；治疗结束后,每3个月进行一次随访,直至随访至患者死亡或满一年,用K-M法计算疾病无进展生存期和1年生存率及中位生存时间。结果：本研究在3个研究中心共纳入研究的患者80例,剔除9例,其中因脑转移所致颅内高压2例,严重肾功能不全1例,拒绝服用中药1例,未经病理确诊的5例。最后接受治疗进入统计分析的患者共有71例。对患者进行体质评估,其中符合气阴两虚体质的患者为24例,符合痰瘀体质的患者为47例。气阴两虚体质患者的中位年龄为73.15岁,痰瘀体质患者的中位年龄为70岁,组间比较具有显著性差异(P<0.05)；71例患者平均接受3.50个周期的治疗,其中气阴两虚体质患者平均接受3.08个周期的治疗,痰瘀体质患者平均接受3.60个周期的治疗；71例患者的临床疗效为CR0例,PR17例、SD33例、PD21例,客观缓解率为23.94%,临床获益率为70.42%；其中气阴两虚体质患者,客观缓解率为12.50%,临床获益率为62.50%；痰瘀体质患者,客观缓解率为29.79%,临床获益率为74.47%；中医临床症状积分不同体质患者各疗程结束后与治疗前比较积分降低,差异均有显著性(P<0.05)。不同体质患者生存质量情况,生理状况、功能状况、情感状况、附加关注状况各疗程结束后与治疗前比较积分增加,差异显著(P<0.05),社会/家庭状况各疗程结束后与治疗前比较差异无显著性(P>0.05)。71位患者的中位疾病无进展生存期为171天(95%CI=126 to 187),1年疾病无进展率为14.19%,中位生存期为269天(95%CI=205 to 404),1年生存率为34.12%。其中气阴两虚体质患者的中位疾病无进展生存期为184天(95%CI=85 to 195),1年疾病无进展率为15.21%,中位生存期为286天(95%CI=206 to 633),1年生存率为38.095%；痰瘀体质患者的中位疾病无进展生存期为171天(95%CI=126 to 186),1年疾病无进展率为13.49%,中位生存期269天(95%CI=176 to 404),1年生存率为32.028%。不良反应轻微,最常见的为Ⅰ-Ⅱ°骨髓抑制,未出现研究相关性死亡。结论：在体质辨证的基础上,气阴两虚体质患者给予单药化疗+益气养阴中药,痰瘀体质患者给予含铂双药化疗+化痰祛瘀中药,能够提高老年晚期NSCLC患者的治疗完成率,改善了患者的临床症状,并能一定程度上提高患者的生存质量,在客观有效率,疾病无进展生存期和1年生存率,相对于文献报道的单纯化学治疗具有一定的优势。更多还原

【Abstract】 Background & Objective:There was no standard chemotherapy for elderly patients of non-small cell lung cancer. MILES research was the biggest clinic research for elderly patients of non-small cell lung cancer all over the world. The result of this research had shown single-agent efficacy with lower toxicity. However another SEER research showed cisplatin-containing regimens could make elderly patients get clinical benefit.From clinical research some pathological physique types are common in different tumor patients in TCM. The most common physiques of elderly patients with lung cancer are phlegm-stagnate type and qi-yin-deficincy type. We depended on the different physique types of advanced non-small cell lung cancer of elderly patients, and offered different combination of traditional Chinese and western medicine therapy. And we hoped these methods to get good clinical results.Patients & Methods:We conducted an open-label,prospective, multicenter trial.To be eligible, patients had to be aged between 65 years and 80 years; to have cytological ly or histologically confirmed NSCLC; to have stageⅢb (with pleural effusion or metastatic supraclavicular lymph nodes)or IV disease. Enrolled between septermber 1st 2009 and March 15th 2011.And fllow-up study closed on March 15th 2012.All patients enrolled this research had received a physique estimate. Patients of qi-yin-deficincy type received single chemotherapy plus herbs of tonifying qi and yin,and patients of phlegm-stagnate type received platinum-based combined chemotherapy plus herbs of dissipating phlegm and removing blood stasis.All treatments were delivered every 3 weeks for a maximum of four cycles.Before the study and after the second cycles of treatments,all patients have to receive radiographic inspection. The patients themselves assessed the functional Assessment of cancer therapy (FACT-L)and doctor assessed clinical syndroms at baseline and 3,6,9 and 12 weeks after the first visit.After treatment follow-up study carried on every 3 months until patients’death or after one year. The primary end point was to compare the cycles of receiving the treatments and response rate. Secondary end points were to compare clinical syndrome,quality of life, progression-free survival and 1 year survival rate with historical documents.Survival cuves were drawn using the Kaplan-Meier method and analyzed by the log-rank test. Results:Of seventy-one patients available for intenion-to-treat analysis, 24 were qi-yin-deficincy type and received single chemotherapy plus herbs of tonifying qi and yin,47 were phlegm-stagnate type and received platinum-based combined chemotherapy plus herbs of dissipating phlegm and removing blood stasis. Patients of qi-yin-deficincy type’s median age are 73.15 years,and patients of phlegm-stagnate type’s median age are 70 years. There are significant difference between two groups (P<0.05). Patients of this research received average 3.50 treatment cycles. The symptoms were improved over time (P<0.05) in both subgroups. There were significant different in the improvement of physical status, emotional status, functional status and additional concerned status between treatment regimens over time (P<0.05), the scores of social/family status in both groups were similar in all before and after treatment (P>0.05), but no difference between two subgroups. During this research objective response rates (complete or partial) and (CR plus PR plus SD) were 23.94% and 70.42%. Objective response rates (complete or partial) were 12.50% and 29.79% in the qi-yin-deficincy type and phlegm-stagnate type arms, respectively. For this research median PFS was 171 days (95% CI=126 to 187) and MST was 269 days (95%CI=205 to 404),1-year survival rate was 34.12% Median PFS was 184 days (qi-yin-deficincy type) and 171 days (phlegm-stagnate type). 1-year survival rate was 38.10% versus 32.03% for qi-yin-deficincy type versus phlegm-stagnate type respectively.The major side effect was bone marrow suppression grade 1-2.There was no death associate with chemotherapy.Conclusion:Patients of qi-yin-deficincy type received single chemotherapy plus herbs of tonifying qi and yin, and patients of phlegm-stagnate type received platinum-based combined chemotherapy plus herbs of dissipating phlegm and removing blood stasis, these kinds of therapies can improve the cycles of receiving the treatments than historical documents.And it can improve the quality of life of patients to certain extent.Also these kinds of methods have a little superiority in objective response rates,PFS and 1-year survival rate compare purely chemotherapy from historical documents.更多还原