Personalized medicine – p53 gene analysis for prediction of response to neoadjuvant therapy in esophageal cancer

Summary

The present review introduces a protocol for a prospective randomized predictive marker clinical trial. The study evaluates the interaction between the proposed predictive marker p53 and response to neoadjuvant chemotherapy in patients with potentially resectable oesophageal cancer. This trial is designed to provide "level of evidence I" data, which are a prerequisite for the clinical implementation of a predictive marker. Despite curative resection, the 5-years survival rates of oesophageal cancer patients do not exceed 20%. Several phase II and III studies have shown that patients who responded to preoperative chemotherapy had a significantly better survival than patients treated with surgery alone. Up till now, it is not possible to identify the responders before commencing treatment. Eighty-four patients with measurable disease will be enrolled in the pANCHO trial. After testing the marker genotype (p53 normal versus p53 mutant), patients will be randomly assigned to receive two different chemotherapies −5FU/Cispaltin or Docetaxel. All patients will be rendered to subsequent surgery and as a primary endpoint response to neoadjuvant treatment will be evaluated. The pANCHO trial is a nationwide academic initiative. The 13 affiliated investigational centres recruited 70% of estimated patients within one year. Patients enrolled in the pANCHO trial benefit from the standardized diagnostic and therapeutic procedures. The study is supposed to identify the need for new guidelines for response assessment in neoadjuvant treated patients. Marker specific results are awaiting autumn 2009 and could be relevant to the choice of therapy in oesophageal cancer.