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背景与目的加速超分割放疗(每日两次方案)联合EP方案同步化疗是美国国立综合癌症网络(National Comprehensive Cancer Network,NCCN)指南推荐的局限期小细胞肺癌的标准治疗方式,但国人对EP方案标准化疗剂量耐受性尚不明确。本研究旨在探讨局限期小细胞肺癌同步放化疗EP方案的最大耐受剂量。方法研究纳入病理证实的局限期小细胞肺癌患者,进行加速超分割放疗同步EP方案(依托泊苷+顺铂)化疗,放疗处方剂量为45Gy/30 f,1.5 Gy/f,每日两次,同一日两次放疗间隔时间≥6 h,5天/周,共3周完成。化疗方案采用依托泊苷联合顺铂,每21天为1周期,具体依托泊苷100 mg/m~2,d1-d3,顺铂采用剂量递增的方式(第1组为70 mg/m~2 d1,第2组为75 mg/m~2 d1)。主要观察指标为治疗期间的血液学毒性。次要观察指标为非血液学毒性和1年总生存期(overall survival,OS)、无进展生存期(progression free survival,PFS)。根据不良事件常用术语评定标准(Common Terminology Criteria for Adverse Events,NCI-CTCAE)4.0,最大耐受剂量设定为6例患者中不超过1例患者出现剂量限制毒性(4级血液学毒性)的剂量,同时下一剂量组6例患者至少2例出现剂量限制性毒性。结果研究共纳入20例局限期小细胞肺癌患者,平均年龄49.50(30-68)岁。第1组入组6例患者,1例患者出现4度中性粒细胞减少;后第2组入组14例患者,1例患者出现4度中性粒细胞减少。其中,第1组有4例患者出现≥3度血液学毒性,1例患者出现3度以上放射性食管炎;第2组有10例患者出现≥3度血液学毒性,无患者出现3度以上放射性食管炎。中位随访9.0个月(3.2个月-36.2个月),1年OS、PFS分别为91%、62%。结论局限期小细胞肺癌患者采用加速超分割放疗联合EP方案化疗将顺铂剂量递增至75 mg/m~2是安全的,其有效性还需要进一步扩大样本量和随访更长的时间来证实。
BACKGROUND & OBJECTIVE Accelerated hyperfraction radiotherapy (twice-daily regimen) Combined with EP regimen is a standard treatment for ST-segment small cell lung cancer recommended by the National Comprehensive Cancer Network (NCCN) guidelines. However, Program standard chemotherapy dose tolerance is not yet clear. The purpose of this study was to investigate the maximum tolerated dose of EP regimen in SCCC. Methods Patients with locally advanced small cell lung cancer (NSCLC) confirmed by pathology were treated with accelerated hyperfractionated radiotherapy (EP) regimen (etoposide plus cisplatin). The prescribed dose of radiation was 45 Gy / 30 f, 1.5 Gy / f twice daily, The same day, two radiotherapy intervals ≥ 6 h, 5 days / week, a total of 3 weeks to complete. Chemotherapy regimen used etoposide combined with cisplatin, every 21 days for a cycle, the specific etoposide 100 mg / m ~ 2, d1-d3, cisplatin dose escalation (group 1 70 mg / m ~ 2 d1, the second group of 75 mg / m ~ 2 d1). MAIN OUTCOME MEASURES Hematological toxicity during treatment. The secondary outcome measures were non-hematologic toxicity and 1-year overall survival (OS) and progression free survival (PFS). According to the Common Terminology Criteria for Adverse Events (NCI-CTCAE) 4.0, the maximum tolerated dose was set at a dose-limiting toxicity (Grade 4 hematological toxicity) dose not exceeding 1 in 6 patients , While dose-limiting toxicity was observed in at least 2 of the 6 patients in the next dose group. Results A total of 20 patients with localized small cell lung cancer were included in the study, with an average age of 49.50 (30-68) years. In group 1, 6 patients were enrolled. One patient had a 4-degree neutropenia. In group 2, 14 patients were enrolled, and 1 patient had a 4-degree neutropenia. Among them, 4 patients in group 1 had ≥3 degree hematologic toxicity, 1 patient had more than 3 degree radiation esophagitis, 10 patients in group 2 had ≥3 degree hematologic toxicity, and no patient showed more than 3 degree radioactivity Esophagitis. The median follow-up was 9.0 months (3.2 months -36.2 months). The 1-year OS and PFS were 91% and 62%, respectively. Conclusions It is safe to use the accelerated hyperfraction radiotherapy combined with EP regimen to increase the cisplatin dose to 75 mg / m ~ 2 in patients with definite stage small cell lung cancer. Its validity needs to be confirmed by further expanding the sample size and following up for a longer period of time.