Neoadjuvant CCRT With/Without Bevacizumab for Locally Advanced ESCC
Status:
Recruiting
Trial end date:
2021-12-01
Target enrollment:
Participant gender:
Summary
Esophageal squamous cell carcinoma (ESCC) is one of the ten leading cancers in Taiwanese
male. The prognosis is poor with a five-year overall survival rate of 10 to 30 %. Randomized
clinical trials have demonstrated that trimodality therapy (TMT), consisted of neoadjuvant
concurrent chemoradiation (CCRT) and radical esophagectomy, improves the overall survival for
patients with locally advanced disease. Despite of the advancement, the outcome remained
unsatisfactory with the median progression-free survival around 20 to 25 months and median
overall survival around 30 months. It is know that the most important prognostic factor is
whether a pathological complete response can be achieved after neoadjuvant CCRT. However, the
use of new generation chemotherapeutic agent taxanes and epidermal growth factor inhibitors
(such as Cetuximab) failed to significantly improve prognosis comparing to the standard
platinum-fluorouracil (PF) regimen. As a consequence, it is mandatory to develop new
chemotherapeutic regimen for CCRT.
In previous prospective studies, investigators used proximal ligation assay technology to
identify serum VEGF-A in correlation with the pathological response and prognosis for
patients receiving neoadjuvant CCRT plus radical esophagectomy for locally advanced ESCC.
Other investigators also showed high VEGF expression correlating to poor outcome. Therefore,
investigators generate the hypothesis that adding vascular endothelial growth factor (VEGF)
monoclonal antibody, Bevacizumab, to standard neoadjuvant CCRT may improve outcome for
patients with ESCC. Meanwhile, several prospective clinical studies have shown the
feasibility, safety, and activity of adding Bevacizumab to chemotherapy, CCRT, or combined
modality therapy including surgery, either in head and neck cancer, esophageal cancer, or
esophagogastric junction adenocarcinoma. However, its efficacy should be further investigated
in larger prospective trials and little is known about the activity and toxicity of
Bevacizumab in ESCC due to small number of reported cases. In the present clinical trial,
investigators plan to investigate whether incorporation of Bevacizumab into standard
neoadjuvant PF-CCRT will improve treatment response and increase pathological complete
response rate. Investigators will also evaluate associated biomarkers in relation to
prognosis. By the present research, investigators expect to develop a new TMT regimen for
this poor prognostic disease.