[Phase I Study of Etoposide and Cisplatin Chemotherapy Dose Escalation â©with Concurrent Twice-daily Radiotherapy for Patients â©with Limited-stage Small Cell Lung Cancer].

: 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45 Gy/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/m2，d1-d3，顺铂采用剂量递增的方式（第1组为70 mg/m2 d1，第2组为75 mg/m2 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/m2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。. METHODS: Patients with histologically proven limited-stage small cell lung cancer (LS-SCLC) were eligible. The patients underwent thoracic radiotherapy (45 Gy, 1.5 Gy bid, 30 fractions for 3 weeks) delivered concurrently with etoposide (100 mg/m2 iv, days 1-3) and cisplatin dose escalating from the two levels ( 70 mg/m2 and 75 mg/m2 on d1). The primary endpoints were hematologic toxicities during treatment. The secondary endpoints were non-hematologic toxicities, overall survival (OS) and progression-free survival (PFS). According to Common Terminology Criteria for Adverse Events 4.0 (CTC-AE 4.0), maximum tolerant dosage (MTD) was defined as the highest safely tolerated dose at which no more than one patient out of six experiences dose-limiting toxicity (Grades 4 hematologic), with the next higher dose having at least two out of six patients experience dose-limiting toxicity. RESULTS: From January 2013 to August 2016, 20 patients were enrolled in this study. The median age was 49.5 (30-68). After the first 6 patients were enrolled in Arm 1 (70 mg/m2 on d1), one patient had Grade 4 neutropenia. Another 14 patients were enrolled in Arm 2 (75 mg/m2 on d1), one patient had Grade 4 neutropenia. The MTD was determined to be etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1). 4 patients had ≥Grade 3 neutropenia and 1 patients had ≥Grade 3 acute esophagitis in Arm 1. 10 patients had ≥Grade 3 neutropenia and no patient had ≥Grade 3 acute esophagitis in Arm 2. All patients with a median follow-up time was 9.0 months, median OS and PFS were not achieved, 1-year OS and PFS were 91% and 61%, respectively. CONCLUSIONS: The MTD of RT with concurrent chemotherapy of EP regimen for patients with LS-SCLC was etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1).
.