A Phase II Study to Assess the Efficacy of Combined Pre-operative Chemo (CPT11, Cisplatin), Radiotherapy (External Beam, Brachytherapy), Plus Surgery for Potentially Resectable Thoracic Esophageal Cancer
Historical surgical series have reported that the chance of cure with surgery alone is
approximately one in four. Many phase II studies and some phase III studies have examined
the role of induction (preoperative) chemotherapy and radiation. In general, these studies
have demonstrated a trend to improved survival using an induction regimen with one phase III
study reporting a significant improvement in survival. Two meta-analyses have failed to
demonstrate a clear advantage of an induction regimen.
When these trials are reviewed, it is apparent that there is a subgroup of patients who are
found at the time of resection to have had a complete pathological response to their
treatment, and these patients clearly experience improved survival.
These previous trials have used older chemotherapy agents. Nevertheless, cisplatin remains
one of the most active drugs available for treating solid tumours. Irinotecan is a newer
drug that has demonstrated significant activity in colorectal cancer and more recently in
esophageal cancer. A previous single institution trial of cisplatin and irinotecan in
esophageal cancer demonstrated a significant response and acceptable toxicity.
By giving one cycle of chemotherapy alone first, it is expected that the dysphagia usually
experienced by these patients will improve sufficiently and that nutritional support, i.e.
feeding tube, will not be required (as has been demonstrated in a previous study of this
drug combination). The same drugs will then be given concurrently with external beam
radiation in order to take advantage of the radiosensitizing properties of both these drugs.
This will be followed by a boost dose of radiation, which will provide a total dose in the
tumourcidal range. Surgery will follow the boost dose of radiation.
This study proposes to combine two drugs with demonstrated activity in esophageal cancer,
cisplatin and Irinotecan, with radiation prior to surgery, with the hypothesis that these
more active agents will offer better control of distant metastatic disease. Their
radiosensitizing properties, when combined with radiation, will improve local control and
provide an increased rate of pathological complete response in patients with surgically
resectable esophageal cancer.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
pathological complete response
Darling E Gail, M.D., FRCSC
University Health Network, Toronto
Canada: Health Canada