以健脾为基础的复方辨证治疗对老年胃癌患者生存期的影响

Survival benefit of an herbal formula for invigorating spleen for elderly patients with gastric cancer

背景:胃癌是最常见的恶性肿瘤之一,中医药已广泛用于胃癌的临床治疗,但尚未见到较大样本临床对照研究对其疗效进行评价。目的:通过对220例老年胃癌预后的分析,研究以健脾为基础的中药复方辨证治疗对老年胃癌预后的影响。设计、场所、受试者和干预措施:采用前瞻性同期病例对照研究方法,将65岁及以上老年胃癌病例(来自上海龙华医院肿瘤一科、瑞金医院消化外科和仁济医院普外科)分为接受中药复方辨证治疗的中药组和未接受中药治疗的非中药组。主要结局指标:依据临床病理分期,是否接受根治性手术和化疗进行分层。运用单因素及Cox多因素回归分析方法分析两组病例的临床病理因素及手术、化疗以及中药治疗对预后的影响。结果:共有220例病例纳入研究。中药组89例,非中药组131例。总体220例病例的Cox多因素回归分析表明,影响老年胃癌患者生存的独立的预后因素分别是临床病理分期、手术方式、化疗和中药治疗(P<0.01)。服用中药的相对危险度为0.322,95%可信区间在0.212～0.489。中药组中位总生存期为41.129个月,1、3、5年生存率分别为85.2%、55.6%、45.7%;非中药组中位总生存期为17.195个月,1、3、5年生存率分别为63.9%、26.9%、21.9%。对未手术或术后复发转移的晚期胃癌分层研究,Cox多因素回归分析示,中药治疗和化疗是影响老年晚期胃癌患者总生存期独立的保护性因素(P<0.01),服用中药的相对危险度为0.421,95%可信区间在0.255～0.693;晚期中药组(36例)中位总生存期为17.819个月,晚期非中药组(60例)中位生存期为8.548个月。对临床病理分期为Ib-Ⅳ(T4N1-3M0、T1-3N3M0)接受根治性手术(R0)且接受3个及以上周期术后辅助化疗病例的分层研究结果显示,术后中药组和术后非中药组的无病生存期和总生存期均未达到中位数,故未作Cox多因素回归分析;术后中药组(33例)1、3、5年无病生存率分别为97.0%、59.9%、50.4%,1、3、5年生存率分别为100.0%、74.1%、61.4%;术后非中药组(69例)1、3、5年无病生存率分别为82.6%、51.1%、51.1%,1、3、5年生存率分别为86.9%、55.6%、55.6%。结论:以健脾为基础的中药复方辨证治疗可改善老年胃癌的总体预后,是老年晚期胃癌预后的有效保护性因子,对老年根治性胃癌术后无病生存期和总生存期的影响需要继续随访评价。

Background： Gastric cancer is one of the most common malignant tumors. Traditional Chinese medicine （TCM） has been widely used in treatment of gastric cancer, but still lacking large sample controlled trial to evaluate its efficacy. Objective： To analyze the prognostic factors of 220 elderly patients with gastric cancer, and to further study the efficacy of an herbal formula for invigorating spleen and its modifications based on syndrome differentiation of TCM in treatment of gastric cancer in elderly patients and the influence on prognosis.Design, setting, participants and interventions： A total of 220 elderly patients aged 65 years or over with gastric cancer from Longhua Hospital of Shanghai University of Traditional Chinese Medicine, and Renji Hospital and Ruijin Hospital of Shanghai Jiao Tong University Medical College were prospectively enrolled. All patients were assigned to either traditional Chinese herbal medicine （TCHM） group （89 cases） or non-TCHM group （131 cases）. Patients in the TCHM group were treated with an herbal formula for invigorating spleen plus chemotherapy, while patients in the non-TCHM group were only treated with chemotherapy. Main outcome measures： Univariate and Cox regression analyses were performed to determine all the potential prognostic factors. Kaplan-Meier curves were used to assess the differences in survival time between TCHM group and non-TCHM group after stratification for TNM stage, surgery or chemotherapy.Results： The 220 eligible patients were histologically confirmed adenocarcinoma of the stomach from 2001 to 2007. Eighty-nine cases in the TCHM group received three or more months of TCHM treatment, and 131 cases in the non-TCHM group did not receive TCHM treatment. Cox regression analysis suggested that the TNM stage, radical resection, three or more treatment cycles of chemotherapy, and TCHM treatment were independent prognostic factors （P〈0. 01）. The patients receiving TCHM treatment demonstrated better prognosis than the other prognostic factors in multivariate analysis; the odds ratio [Exp（13）] of overall group wasO.322, and 95% confidence interval （Cl） was from 0.212 to 0.489. Median overall survival of TCHM group was 41. 129 months, and one-, three-, and five-year survival rates were 85.2%, 55.6% and 45.7% respectively. Median overall survival of non-TCHM group was 17. 195 months, and one-, three-, and five-year survival rates were 63.9%, 26.9% and 21.9% respectively. In stratification analysis of stage for 96 patients who did not accepted radical resection or suffered from recurrence and metastasis （36 cases in the TCHM group, and 60 cases in the non-TCHM group）, Cox regression analysis suggested that three or more treatment cycles of chemotherapy and TCHM treatment were independent prognostic factors for improving survival respectively （P〈0.01）. The hazard ratio [Exp（[3）] of TCHM in stratification for late stage was 0.421, and 95% confidence interval was from0.255 to0.693. Median overall survivals were 17. 819 months for TCHM group and 8. 548 months for non-TCHM group. In stratification analysis of surgery and chemotherapy for 102 patients with Ib-IV （MO） who accepted radical resection （R0 resection） and three or more treatment cycles of chemotherapy （33 cases in the TCHM group, and 69 cases in the non-TCHM group）, the disease-free survival and overall survival did not reach the median at the time of analysis. In the TCHM group, one-, three-, and five-year disease-free survival rates were 97.0%, 59. 9% and 50.4%, and one-, three-, and five-year survival rates were 100.0%, 74. 1% and 61. 4%, respectively. In the non-TCHM group, one-, three-, and five-year disease-free survival rates were 82.6%, 51.1% and 51.1%, and one-, three-, and five-year survival rates were 86.9%, 55.6% and 55.6%, respectively. Conclusion： The herbal formula for invigorating spleen has an important value for improving the prognosis of elderly patients with gastric cancer. This herbal formula shows survival benefit for advanced gastric cancer in elderly patients. The influence of TCHM on disease-free survival and overall survival of postoperative gastric cancer in elderly patients need to be further evaluated.