加速超分割放疗加化疗治疗局限期小细胞肺癌临床Ⅱ期试验结果分析

Hyperfractionated accelerated radiotherapy combined with cisplatin/etoposide chemotherapy for limited small cell lung cancer:a phase Ⅱ clinical trial

目的 研究加速超分割放疗加化疗治疗局限期小细胞肺癌的耐受性、副反应和疗效。方法 5 7例中男 5 0例 ,女 7例 ,中位年龄 6 0岁。放疗为 1.4Gy/次 ,2次 /d ,间隔 >6h ,5d/周 ;总剂量为 5 6Gy,4 0分次 ,4周完成。照射剂量未经肺和空气等不均匀组织密度校正。化疗采用EP(依托泊甙5 0～ 70mg/m2 ,第 1～ 3天 ;顺铂 2 5～ 30mg/m2 ,第 1～ 3天 )方案 ,总共 6个周期。结果 3例未完成既定治疗计划。完成化疗周期数中位值为 6个 ,中位间期为 4 .9周。急性放射性食管炎发生率为 72 % ,其中 3级为 7%。急性放射性肺炎发生率为 6 4 % ,其中 3级为 4 %。中位生存时间为 2 4个月 ,1、2、3年生存率分别为 81%、4 9%、2 1%。 13例发生局部复发 ,9例在照射野内 ,4例在野外。 1、2、3年局部控制率分别为 85 %、74 %、6 8%。 4 4例远地转移 ,其中 6 6 %的部位在脑。 1、2、3年远地转移率分别为31%、5 9%、79%。结论 加速超分割放疗加化疗能为局限期小细胞肺癌患者所耐受 ,局部控制和生存有所改善 ;

Objective A phase Ⅱ clinical trial on hyperfractionated accelerated radiation therapy (HART) combined with cisplatin/etoposide chemotherapy was conducted to evaluate its feasibility, toxicity , tolerance, and the efficacy for limited small cell lung cancer (LSCLC). Methods The HART schedule consisted of 1.4?Gy/fraction, twice per day with >6 hour interval, five treatment days per week, to a total dose of 56?Gy/40 f/4 w. Radiation dose was prescribed at isocenter with no correction for tissue inhomogeneity. Chemotherapy consisted of cisplatin 252?0?mg/m 2 from d1 to d3 and etoposide 50-70?mg/m 2 from d1 to d3 for 6 cycles. Fifty-seven patients were eligibly registered in this trial. All were in limited stage with a median age of 60 years. Of these 57 patients, 3 patients were withdrawn from the study due to development of distant metastasis, grade 3 thrombocytopenia and financial problems. Results Fifty-four patients completed the planned treatment. A median of 6 cycles of chemotherapy was administered with a median interval of 4.9 weeks. The most common acute complication was radiation esophagitis, which occurred in 41 pateients(72%), with Grade 3 in 4 (7%). Thirty-six patients had acute pulmonary toxicity(64%), with Grade 3 in 2 (4%). The median survival time was 24 months. The 1-, 2-,and 3-year survival rates were 81%, 49% and 21%, respectively. Of 57 patients, 13 patients had loco-regional progression, 9 within the radiation fields and 4 outside of the radiation fields. The 1-, 2-,and 3-year loco-regional progression-free rates were 85%, 74% and 68%, respectively. Distant metastasis occurred in 44 patients, 66% to the brain. The 1-, 2-,and 3-year distant metastasis rates were 31%, 59% and 79%, respectively. Conclusions Hyperfractionated accelerated radiation therapy is well tolerated by limited small cell lung cancer patients. Increase in chemotherapy cycles might make up for the less intensity in radiotherapy dose and interval spaced between radiotherapy and chemotherapy.