CODE方案密集周化疗和多学科综合治疗小细胞肺癌

Patients with small-cell lung cancer managed with the CODE regimen of intensive weekly chemotherapy and multidisciplinary comprehensive therapy

目的探讨CODE方案密集周化疗及多学科综合治疗小细胞肺癌(small cell lung cancer,SCLC)的疗效及生存预后因素。方法 1995年3月至2005年12月入组SCLC患者118例,其中男性86例(72.9%),女性32例(27.1%),中位年龄55岁,局限期(LD)30例(25.4%),广泛期(ED)88例(74.6%),所有患者均有病理或细胞学诊断。周化疗药物包括顺铂、长春新碱、阿霉素及依托泊苷,主要通过增加给药频率增加药物剂量强度,总疗程为9周。CODE方案疗效达CR或PR即可接受胸部放疗(RT),放疗后患者KPS>60,再行维持治疗(MCT)。11例患者于CODE前或后进行了手术。对CODE及综合治疗均按实体瘤疗效评定。应用Kaplan-Meier法绘制生存曲线,寿命表法计算生存率,COX多因素回归比例风险模型进行了生存预后因素分析。结果对110例患者进行了CODE疗效评定,其中CR 17例(15.5%),PR 79例(71.8%),PD 5例(4.5%),不良反应轻微。主要治疗模式是CODE+RT+MCT,总计83例(70%)。105例(89%)患者对CODE+多学科治疗有效,CR 29例(25%),PR76例(64%)。118例SCLC患者的中位生存期(MST)为21个月(95%CI:17.5～24.6),ED为17个月(95%CI:12.4～21.6),LD 38个月(95%CI:12.2～63.8),P=0.000。ED、LD 1年生存率分别为70.5%和93.3%(P=0.022),5年生存率为12.5%和40%(P=0.003)。单因素及COX多因素分析显示疗效、治疗模式及疾病分期与患者生存密切相关。结论 SCLC患者经CODE及多学科综合治疗生存明显延长。CODE方案是SCLC重要的内科治疗,且耐受性好。早期的SCLC可选择外科治疗。维持治疗的临床研究值得进一步探讨。

Objective To retrospectively evaluate the efficacy and prognostic factors of the intensive weekly chemotherapy plus multidisciplinary comprehensive therapy for patients with small-cell lung cancer （ SCLC ）. Method 118 SCLC patients were recruited at PUMC hospital from March 1995 to December 2005, of which 30 patients （ 25.4% ） had limited-disease （LD） and 88 （74. 6% ） had extensive-disease （ ED）, 86 patients （72. 9% ） were male and 32 （27. 1% ） were female, the median age was 55 years old. The intensive weekly regimen with cisplatin, vincristine, doxorubicin, and et- oposide （CODE） was designed for all patients. The optimal dose intensity was attained through frequent administrations. The duration of chemotherapy was 9 weeks. Patients achieved CR or PR as per WHO criteria after chemotherapy were to receive thoracic radiotherapy （RT）. Patients with good performance status （KPS 〉 60） after RT followed by maintainence chemother- apy （MCT）. The surgical operations were performed for 11 patients. The survival was analyzed by Kaplan-Meicr and prog- nostic factors by COX multivariate regression. Result 1 l0 patients were evaluated in CODE regimen： 17 patients （15.5%） had CR disease, 79 patients （71.8%） had PR disease, and 5 patients （4. 5% ） had PD, no serious adverse event was found. 83 patients （70%） were treated with CODE ＋ RT ＋ MCT, 105 patients （89%） responded to CODE and muhidiscipli- nary comprehensive therapy, of that 29 patients （25%） attained CR and 76 patients （64%） achieved PR. The median overall survival was 21 months （95% CI： 17. 5-24. 6） in all patients, of which 17 months （95% CI： 12.4-21.6） in patients with ED and 38 months （95% CI： 12. 2 -63.8） （P =0. 000） in LD. One year survival rate of patients with ED and LD were 70. 5% and 93. 3% （P =0. 02） respectively. Five year survival rate of patients with ED and LD were 12.5% and 40% （ P = 0. 003 ） respectively. Monofactor and multifactor COX regression showed that curative effect, model of therapy, and dis- ease stage were factors correlated with survival. Conclusion The patients with SCLC intensive weekly chemotherapy （CODE） and muhidisciplinary comprehensive therapy was well tolerated and had preferable median overall survival. Patients with early SCLC disease benefit from surgical operation. Maintenance with MCT worth further investigation.