一线化疗后替吉奥维持治疗晚期食管癌疗效观察

发布时间：2018-07-22 13:07

【摘要】：背景和目的食道癌是全世界癌症死亡的第六主要原因,在中国尤其常见[1]。然而,与西方国家和日本相比,我们远远落后于时代,贡献最少的A级证据[2-3]。与其他胃肠道恶性肿瘤相比,食管癌由于早期淋巴结和远处器官转移而呈现出高度恶性。局部晚期或广泛转移食管癌因其严重侵袭周围器官、进展迅速且患者因进食困难造成营养状况差而难以治疗继而导致预后差[4-5]。相关文献显示食管癌患者的5年生存率仅为5%-30%[5]。以往,食管切除术在早期和局部食管癌治疗中起着关键作用,但对于老年患者,食管切除术的应用却日益减少[6-8],这是因为大多数患者在确诊时已属于晚期,失去了最佳手术机会[9]。过去的10到15年中已完成的临床试验表明,除了手术切除之外还存在一些可以提高晚期食管癌患者生存期的治疗方案[10-11]。化学治疗,对食管癌患者来说起着十分重要的作用。一般而言,氟尿嘧啶联合铂类被视为晚期食管癌的标准一线化疗方案,其反应率可达25%-45%[12-16],但中位生存期却不到一年[17-19]。然而,大多数患者在标准一线化疗后迅速发生转移或复发,随后进行二线化疗[20-22],但是研究发现二线化疗疗效远不如一线化疗。怎样才能延长一线化疗后疾病进展时间呢?对于那些在化疗中获益的患者的后续治疗,过去曾经采取“观望并等待”的模式。但最近几年,借鉴血液学肿瘤的成功治疗模式[9],应用高效、低毒的单药作为对实体肿瘤的维持治疗已经应用于晚期卵巢癌、晚期结直肠癌、晚期非小细胞肺癌、晚期胃癌、胰腺癌中,结果表明维持治疗可延长疾病无进展生存期,甚至可能达到生存获益[23-24]。但目前针对食管癌的维持治疗却较少报道。卡培他滨是一种口服氟尿嘧啶类药物[25-27],相关试验表明卡培他滨维持治疗可延长晚期食管癌患者的无进展生存期和总生存期[28]。替吉奥(S-1)是一种口服复方氟尿嘧啶衍生物,最早由日本大鹏药品工业株式会社研制,S-1是替加氟、吉美嘧啶和奥替拉西钾的混合物,摩尔比为1:0.4:1[29-31]。替加氟是一种口服5-FU前体药物;吉美嘧啶是二氢嘧啶脱氢酶抑制剂,可增强5-FU的作用;奥替拉西钾可以减少5-FU的胃肠毒性。因此,从整个配方结构,S-1既可增强抗肿瘤作用,延长作用时间,同时也降低了胃肠道毒性[32-33]。到目前为止,S-1已被广泛应用在各种癌症中,如头颈部癌,肺癌和胰腺癌等[34-36]。S-1与顺铂的联合化疗已被确立为胃癌的标准化疗方案[37-39]。S-1用于胰腺癌、胃癌、结直肠癌等消化道肿瘤的维持治疗在中外期刊上也见报道[40-41]。基于上述事实,我们有理由认为,对于食管癌患者,S-1是一个很有潜力的维持治疗药物。本研究通过对2012.01到2015.12的66例晚期食管癌患者应用S-1维持治疗的临床资料进行回顾性分析,探讨S-1维持治疗的临床疗效、不良反应。资料与方法研究对象为2012年1月1日—2015年12月31日郑州大学第一附属医院肿瘤内科收治的经病理学确诊为晚期食管癌的66例患者,既往均接受过顺铂联合氟尿嘧啶方案一线化疗4~6个周期后,疗效评价为完全缓解、部分缓解或疾病稳定,其中31例继续接受S-1单药口服维持治疗直至疾病进展或出现不能耐受的不良反应(S-1维持治疗组),另35例接受最佳支持治疗(对照组)。观察疾病反应率、疾病控制率、无进展生存期、总生存期及不良反应。统计学方法所有数据均采用SPSS17.0统计学软件进行分析,分类资料采用χ2检验,生存分析采用Kaplan-Meier法。P0.05为差异有统计学意义。结果1.S-1维持治疗组的客观反应率为22.6%,优于对照组的3.9%(P0.05)。2.S-1维持治疗组的疾病控制率为38.7%,尽管高于对照组的22.9%,但差异无统计学意义(P0.05)。3.S-1维持治疗组的中位无进展生存期为17.0个月,优于对照组的10.0个月(P0.05)。4.S-1维持治疗组的主要毒副反应为恶心、呕吐、贫血、白细胞减少和手足综合征等,经对症治疗后均好转,无治疗相关性死亡病例出现。结论一线治疗后继续替吉奥单药维持治疗晚期食管癌,可提高近期有效率,延长中位无进展生存期,不良反应可以耐受。
[Abstract]:Background and objective esophagus cancer is the sixth main cause of cancer death in the world. In China, [1]. is especially common, however, compared with the western countries and Japan, we are far behind the times. Compared to the other gastrointestinal malignancies, the least contribution of the A-level evidence, [2-3]., presents a high level of early lymph node and distant organ metastasis. Malignant. Locally advanced or widely metastatic carcinoma of the esophagus, due to its severe invasion of the peripheral organs, is progressing rapidly and the patient is poor in nutritional status due to the difficulty of eating. The poor prognosis of the patients leads to poor prognosis, [4-5]. related literature shows that the 5 year survival rate of esophageal cancer patients is only 5%-30%[5].. Esophagectomy has been used in early and local esophageal cancer treatment. There is a key role, but for elderly patients, the use of esophagectomy is increasingly reduced by [6-8], because most patients are late at the time of diagnosis and lose the best chance of operation, [9]. has completed the past 10 to 15 years of clinical trials showing that there are some patients with advanced esophageal cancer besides surgical excision. [10-11]. chemotherapy is very important for patients with esophageal cancer. Generally speaking, fluorouracil combined with platinum is considered as a standard first-line chemotherapy regimen for advanced esophageal cancer, with a response rate of up to 25%-45%[12-16], but the median survival time is less than one year [17-19]., but most of the patients are in the standard line. There is a rapid metastasis or recurrence after treatment, followed by a second line chemotherapy [20-22], but the study has found that second line chemotherapy is far less effective than first-line chemotherapy. How can we extend the time for disease progression after first-line chemotherapy? For patients who benefit from chemotherapy, follow-up treatment has been "wait-and-see" in the past, but in recent years, Using the successful treatment model [9] for hematological tumors, the application of high efficient, low toxic single drug as a maintenance therapy for solid tumors has been applied to advanced ovarian cancer, advanced colorectal cancer, advanced non-small cell lung cancer, advanced gastric cancer, and pancreatic cancer. The results indicate that maintenance treatment can not survive and even achieve survival benefit. [23-24]. but current treatment for esophageal cancer is less reported. Capecitabine is an oral fluorouracil drug [25-27]. Related trials suggest that capecitabine maintenance therapy prolongs the progression free survival of patients with advanced esophageal cancer and the total survival time [28]. teggio (S-1) is an oral compound fluorouracil derivative, the earliest S-1 is a mixture of tegafon, pyrimidine and oretirase, the mole ratio is 1:0.4:1[29-31]. tegafur, an oral 5-FU precursor drug; gimilacil is a two hydrogen pyrimidine dehydrogenase inhibitor, which can enhance the effect of 5-FU; thus, oretiari potassium can reduce the gastrointestinal toxicity of 5-FU. Therefore, from the whole, from the whole The combination of [34-36].S-1 and cisplatin, such as head and neck cancer, lung cancer and pancreatic cancer, has been widely used in various cancers, such as head and neck cancer, lung cancer and pancreatic cancer, and the combined chemotherapy of [34-36].S-1 and cisplatin, such as head and neck cancer, lung cancer and pancreatic cancer, has been established as the standard chemotherapy for gastric cancer, [37-39].S-1 is used in the pancreas for the use of S-1. The maintenance treatment of digestive tract tumors such as adenocarcinoma, gastric cancer and colorectal cancer is also reported in Chinese and foreign periodicals. [40-41]. is based on the above facts. We have reason to think that S-1 is a potential maintenance therapy for patients with esophageal cancer. This study is based on the application of S-1 maintenance therapy to 66 patients with advanced esophageal cancer in 2012.01 to 2015.12. The clinical efficacy and adverse reactions of S-1 maintenance treatment were analyzed retrospectively. 66 patients with advanced esophageal cancer confirmed by pathology from January 1, 2012 to December 31, 2015 in the First Affiliated Hospital of Zhengzhou University were treated with cisplatin combined with fluorouracil. After line chemotherapy for 4~6 cycles, the curative effect was evaluated as complete remission, partial remission or disease stability, of which 31 cases continued to accept S-1 single drug oral maintenance therapy until disease progression or intolerance (S-1 maintenance treatment group), and the other 35 cases received optimal support treatment (control group). The survival period, the total life period and the adverse reaction. All the statistical methods were analyzed by SPSS17.0 statistics software. The classification data were tested by chi 2, and the survival analysis using the Kaplan-Meier method.P0.05 was statistically significant. Results the objective response rate of the 1.S-1 maintenance group was 22.6%, which was better than the control group of 3.9% (P0.05).2.S-1 maintenance. The rate of disease control in the treatment group was 38.7%, although it was higher than 22.9% in the control group, but the difference was not statistically significant (P0.05) the median progression free survival of the.3.S-1 maintenance group was 17 months, and the major side effects of the 10 months (P0.05) group of the control group were nausea, vomiting, anemia, leukocyte reduction and hand foot syndrome. After treatment, there was no treatment related death cases. Conclusion after first-line treatment, continuing the treatment of advanced esophageal cancer with monotherapy, can improve the short-term efficiency, prolong the median progression free survival and tolerable adverse effects.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.1

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