title: [Phase I Study of Etoposide and Cisplatin Chemotherapy Dose Escalation  with Concurrent Twice-daily Radiotherapy for Patients  with Limited-stage Small Cell Lung Cancer].
abstract: BACKGROUND
  Concurrent twice-daily radiotherapy with chemotherapy of EP regimen is one of the current standard treatments for limited-stage small cell lung cancer. However, the safely tolerated dose of standard chemotherapy for Chinese patients is not decided. This study was to evaluate the toxicity and the maximum tolerated dose (MTD) of etoposide and cisplatin concurrent with thoracic radiation therapy for patients with limited-stage small cell lung cancer.
  
  
  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). .
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Jing
authors.initials: J
authors.lastname: You
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Huiming
authors.initials: H
authors.lastname: Yu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Maxiaowei
authors.initials: M
authors.lastname: Song
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shi
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Anhui
authors.initials: A
authors.lastname: Shi
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D012449:Safety; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005047:Etoposide; D002945:Cisplatin