【摘要】 目的探讨替吉奥单药在晚期非小细胞肺癌三线治疗的临床疗效及不良反应。进一步研究肺癌患者替吉奥代谢相关酶表达水平与替吉奥疗效及毒性反应相关性。方法搜集2010年1月至2014年12月我院共60例经病理学或组织学确诊的非小细胞肺癌患者进行随机对照研究。所有患者均为二线或二线以上治疗失败的患者,既往患者接受过含铂类化疗方案(不包含分子靶向治疗)。患者随机分为2组,实验组30例患者据体表面积接受替吉奥胶囊口服,即BS<1.25 m2予80 mg/d,1.25 m2≤BS<1.5 m2时予100 mg/d,BS≥1.5 m2时予120 mg/d,分2次口服,d1~14,每21 d为1个周期,至少完成2个周期,抽外周血检测二氢嘧啶脱氢酶(DPD)活性,胸苷磷酸化酶(TP)及胸苷酸合成酶(TS)的表达情况,均接受最佳的支持治疗。对照组30例患者只接受最佳的支持治疗。结果实验组患者疾病控制率(CR+PR+SD)为26.67%(8/30),中位无进展生存期(m PFS)为2个月,中位生存期(MST)为5个月。单纯支持治疗组m PFS和MST分别为1个月、3个月。两组比较实验组MST较对照组延长2个月,有统计学意义(P<0.05),而实验组m PFS较对照组延长0.5个月,无统计学差异(P>0.05)。实验组患者替吉奥不良反应主要为消化道及血液学毒性,所有不良反应均无Ⅳ度情况发生。血DPD活性与实验组不良反应无明显相关性(P>0.05)。实验组TP(+)者总生存时间(OS)及无进展生存时间(PFS)均优于TS(-)者,但无统计学意义(P>0.05)。实验组TS(+)者总生存时间(OS)及无进展生存时间(PFS)优于TS(-)者,有统计学意义(P<0.05)。结论替吉奥治疗三线及以上晚期非小细胞肺癌效有一定的疗效,不良反应可耐受,值得临床推广。TP、TS检测对预测替吉奥用于肺癌患者的预后有一定的指导意义。更多还原

【Abstract】 Objective To observe the efficacy and toxicity of an oral anticancer fluoropyrimidine derivative(S-1) for previously treated patients with advanced non-small cell lung cancer(NSCLC). To investigate the relationship between the activities of dihydropyrimidine dehydrogenase(DPD) and the toxicity, the level of the thymidylate synthas(TS), thymidine phosphorylase(TP) and the sensitivity of chemotherapy. Methods The records of non-smallcell lung cancer patients who had received S-1 monotherapy between in January 2010 to Decembe 2014. ALL the patients who were advanced non-smallcell lung cancer had previously received second-or further-line chemotherapy. Thirty cases of them were give S-1 for fourteen consecutive days and received seven days of drug-free period(twenty-one days in one course). The drug was administered in two divided doses daily at 80 mg/day for patients with a body surface area<1.25 m2,100 mg/day for those with a body surface area of 1.25-1.5 m2, and 120 mg/day for those with a body surface area >1.5 m2. They were completed at least 2 cycles and received best supportive care. The other thirty cases were only received best supportive care after failure of second- or futherline chemotherapy. Results In the thirty cases who were give S-1, the disease control rates(CR+PR+SD) were 26.67%(8/30). The median progressionfree survival time(m PFS) was 2.0 months, and the median survival time(MST)was 5.0 months. In the thirty cases who had received best supportive care, the m PFS and MST were 1.0 and 3.0 months respectively. Between the two groups, the m PFS were not statistically different, the MST were statistically different. The toxicity profile of S-1 was mild, and grade 3 or more severe toxicity was rare. The main side effects were gastrointestinal reaction and bone marrow suppression, no Ⅳ adverse reactions occur. The S-1 associated toxicities had a negative relationship with DPD activity in blood. The TP(+) and Ts(+) patients had longer overall survival(OS) and Progression-free survival(PFS) than that of TP(-) and Ts(-) patients respectively. Conclusion S-1 exhibits modest activity and acceptable toxicity when used as a third or subsequent line of chemotherapy in patients with advanced NSCLC. Expression of thymidylate synthase(TS), thymidine phosphorylase(TP) can predict for clinical outcome of fluoropyrimidine-based therapy.更多还原