Docetaxel, Oxaliplatin, Capecitabine, Fluorouracil, and Radiation Therapy in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

• Pathologic complete response rate [ Designated as safety issue: No ]
  

• Overall survival [ Designated as safety issue: No ]
  
• Disease-free survival [ Designated as safety issue: No ]
  
• Adverse events [ Designated as safety issue: Yes ]
  
• Clinical tumor response (complete and partial response) [ Designated as safety issue: No ]
  
• Pharmacogenetic and proteomic marker measures [ Designated as safety issue: No ]
  
• PET measure profiles including standardized uptake values and %-injected dose of tumor volume [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Assess and compare the pathologic complete response rate of sequential docetaxel, oxaliplatin, and capecitabine followed by fluorouracil, oxaliplatin, and radiotherapy versus fluorouracil, oxaliplatin, and radiotherapy alone in patients with potentially resectable advanced adenocarcinoma of the esophagus, gastroesophageal junction, or gastric cardia.

Secondary

• Assess the adverse event profile and safety of these regimens in this patient population.
• Assess and compare the overall survival of patients treated with these regimens.
• Assess and compare the disease-free survival between treatment arms.
• Assess and compare the clinical tumor response rate of these proposed regimens when administered before surgery between treatment arms.
• Evaluate the profiles of pharmacogenetic and proteomic marker measures over time, and assess the association of changes in these biomarkers induced by these proposed regimens with pathologic tumor response and other outcomes of interest.
• Evaluate the profiles of FDG PET/CT measures, including standardized uptake values and % injected dose in the tumor volume over time, and assess the correlation of changes in PET measures with pathologic tumor response and other outcomes of interest.

OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0-1 vs 2), and disease stage (II vs III/IVA). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive docetaxel IV over 1 hour and oxaliplatin IV over 2 hours on day 1. Patients also receive oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive fluorouracil* IV continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy** 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiotherapy, patients undergo surgery.
• Arm II: Patients receive fluorouracil IV continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy and then surgery as in arm I.* NOTE: * Fluorouracil continuous IV infusion begins within 24 hours of radiotherapy and ends within 24 hours of radiotherapy completion.

NOTE: ** Radiotherapy should begin within 2-6 weeks after completion of 2 courses of docetaxel, oxaliplatin, and capecitabine.

Blood samples are collected at baseline and periodically during study for pharmacogenetic (genetic polymorphisms along with drug target pathways) and proteomic markers (microRNA and mRNA expression) studies. Tumor tissue samples from biopsy and surgery are also collected for pharmacogenetic and proteomic markers studies and future correlative studies.

After completion of study therapy, patients are followed up every 3-6 months for 2 years.