title: Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer.
abstract: OBJECTIVE
  To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma.
  
  
  METHODS
  According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity.
  
  
  RESULTS
  In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea.
  
  
  CONCLUSIONS
  Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies.
authors.affiliation: 1 Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China ; 2 National Center for Anticancer Drugs Clinical Study, Beijing 100021, China ; 3 Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors.forename: Yihebali
authors.initials: Y
authors.lastname: Chi
authors.affiliation: 1 Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China ; 2 National Center for Anticancer Drugs Clinical Study, Beijing 100021, China ; 3 Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Yang
authors.affiliation: 1 Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China ; 2 National Center for Anticancer Drugs Clinical Study, Beijing 100021, China ; 3 Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yang
authors.affiliation: 1 Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China ; 2 National Center for Anticancer Drugs Clinical Study, Beijing 100021, China ; 3 Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors.forename: Yongkun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 1 Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China ; 2 National Center for Anticancer Drugs Clinical Study, Beijing 100021, China ; 3 Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jia
authors.affiliation: 1 Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China ; 2 National Center for Anticancer Drugs Clinical Study, Beijing 100021, China ; 3 Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Shi
keywords: FOLFOX4; Sorafenib; gastric cancer