铂类加5-FU为主的DLF、CLF及DFM方案治疗晚期食管癌的临床研究

Clinical Evaluation of DLF,CLF and DFM Regimens Based on Platinum Compound plus 5-fluorouracil for Treatment of Advanced Esophageal Carcinoma

背景与目的:顺铂(cisplatin,DDP)联合氟尿嘧啶(5-fluorouracil,5-FU)被认为是中晚期食管癌化疗的标准方案,本研究采用以铂类加5-FU为主的DLF、CLF及DFM方案治疗晚期食管癌,探讨这三个方案在晚期食管癌治疗中的价值并分析影响晚期食管癌的预后因素。方法:1999年10月至2004年12月,对入选的98例晚期食管癌进行非随机分组接受相应治疗。DLF方案:醛氢叶酸(CF,200mg/m2,d1)静脉滴注2h加5-FU0.5g静脉推注及5-FU3.0g/m2持续48h滴注联合DDP(80mg/m2)静脉滴注,共48例;CLF方案:DLF方案中的DDP替换为卡铂(CBP,AUC=5,d1),共32例;DFM方案治疗:DDP(80mg/m2)加平阳霉素(5mg/m2,d1,3,5)联合5-FU(0.4g/m2,d1～5),共18例。疗效、不良反应的分析比较采用卡方检验,生存分析采用Kaplan-Meier法,预后因素分析采用Cox回归模型。结果:全组98例均可进行疗效和不良反应评价,总有效率为50.00%,DLF、CLF及DFM方案有效率分别为60.42%、46.86%及27.78%(DLF对DFM,P=0.027)。主要不良反应为恶心呕吐、脱发、骨髓抑制及口腔粘膜炎,CLF方案恶心呕吐显著低于DLF、DFM方案。中位随访时间为9个月,全组总的中位生存期为9个月(95%CI,6.67～11.33个月),采用DLF、CLF及DFM方案治疗患者中位生存期分别为10、9、7个月(P=0.740)。年龄、性别、病理类型及治疗方案对生存均没有影响(P>0.05),而转移或病变部位、治疗前功能状态是影响预后的相关因素(P值分别为0.026和0.000),淋巴结、软组织及骨转移比内脏器官转移预后好,而治疗前功能状态较好者(KPS≥80)经治疗预后较好,功能状态较差者预后也差,从治疗中获益较少。结论:DLF方案疗效较好,不良反应可以耐受,可作为晚期食管癌化疗的一线化疗方案;CLF方案不良反应较低,尤其适用于年老体弱者。

BACKGROUND ＆ OBJETIVE： Combination chemotherapy with 5-fluorouracil （5-FU） and cisplatin is regarded as the standard regimen for advanced esophageal carcinoma. This study was to evaluate the efficacy and safety of DLF, CLF and DFM regimens, based on platinum compound plus 5-fluorouracil in the treatment of advanced esophageal carcinoma, and to further explore prognostic factors of advanced esophageal carcinoma. METHODS： From October 1999 to December 2004, 98 patients with advanced esophageal carcinoma were enrolled in the study. They were non-randomly assigned to receive a 2-hour infusion of folinic acid 200 mg/m^2, followed by a 5-FU bolus 400 mg/m^2 and 48-hour infusion of 5-FU 3 000 mg/m^2 every 3 weeks, combined with cisplatin 80 mg/m^2 （DLF, n=48） or with carboplatin AUC=5 on day 1 （CLF, n=32）, or with cisplatin 80 mg/m^2, 5- fluorouracil bolus 400 mg/m^2 on day 1-5 plus pingyangmycin 5 mg/m^2 on day 1,3,5 （DFM, n=18）. Survival analysis and prognostic factors were evaluated by Kaplan-Meier method and Cox regression analysis. RESULTS： All 98 patients were assessable for response and toxicity. There were 13 complete response, 36 partial response, 45 no changes and 4 progressive disease with a total response rate of 46.86%. The response rates of DLF, CLF and DFM regimens were 60.42% ,46.86% and 27.78%, respectively （DLF vs DFM,P=0.027）. The major side effects were nausea-vomiting, alopecia, bone marrow suppression and mucositis, and the others were uncommon. All side effects were tolerable and mild except for nauseavomiting. Nausea-vomiting was mildest in CLF among the three regimens. After a median follow-up of 9 months, the overall median survival was 9 months （95% CI, 6.67 to 11.33 months）, the median survival of the patients treated with DLF, CLF or DFM regimen was 10, 9 and 7 months, respectively （P=0.7402）. Better prognosis was correlated with good conditions of patients before chemotherapy （KPS ≥ 80, P=0.000） and metastasis to lymph node, parenchyma or bone in stead of visceral organs （P=0.026）. There was no correlation between the prognosis and age, sex, types of pathology and the regimen of therapy. CONCLUSIONS： The DLF regimen is tolerable and more effective, thus could be recommended as a front-line standard treatment for advanced esophageal carcinoma. The CLF regimen is more suitable for feeble and older patients since it has the mildest side effects. The prognostic factors of advanced esophageal carcinoma include conditions before chemotherapy and the location of metastasis.