A Phase II Study of Concurrent Chemoradiotherapy With Weekly Docetaxel and Cisplatin in Inoperable Esophageal Cancer
Chemotherapy can provide significant palliation of symptoms for patients with unresectable,
locally advanced or metastatic esophageal cancer. Cisplatin and continuous infusion 5 FU,
alone or combined with radiotherapy, is the most frequently used regimen. The response rate
reported with cisplatin and 5 FU ranged from 35 to 40% ,whereas the 2-year survival rates of
patients with locally advanced esophageal cancer ranged from 8 to 55%, with a mean 27%.
Therefore, there is a need to test new combination, specifically in unresectable locally
advanced esophageal patients, with the aim of increasing the pCR rate and survival.
Cisplatin had been widely used as radiosensitizer and Docetaxel is different from that of
cisplatin -5FU and and has proved to have an additive effect with cisplatin and
supra-additive antitumor activity with fluorouracil in vitro and in murine models. To
investigate the feasibility of combining concomitant radiation with docetaxel and cisplatin
and assess the regimen's toxicity, locoregional control rate, and survival in patients with
locally advanced or metastatic esophageal cancer.In this study, docetaxel 25mg/m2 is given
with 500ml normal saline , as a 1hr infusion, on days 1,8 of every 3 weeks. Cisplatin75mg/m2
is given by intravenous infusion in 500 mL of 5% dextrose solution over 60 minutes on day 1
of every 3weeks.. Therapy will be repeated every 21 days. Radiation therapy (200cGy/day upto
5400 cGy) begin on the first day of week 1 over 6 weeks (concomitant chemoradiation
therapy). When the investigators assume that standard treatment's response rate is 50% and
the response of experimental treatment is 75% and use Simon's two-stage optimal design under
the significance level of 5% and the power of 80%, the total sample size of 25 is at least
required. For a total of 25 subjects, 11 will be accrued during stage 1 and 14 during stage
2. If 6 or fewer responses are observed during the first stage then the trial is stopped
early. If 16 or fewer responses are observed by the end of the trial then no further
investigation of the drug is warranted. If the investigators assumed that the drop out rate
was 10%, number of subjects per treatment arm will be 28.
Time Perspective: Prospective
Chest and abdominal CT and EGD were obtained to assess tumor status, 4 to 6 weeks after the completion of CRT. The patients who were documented on the CT scan and upper gastrofibroscopy as showing a complete response (CR) underwent positron emission tomography (PET)-CT. If the PET-CT showed no metabolic evidence of malignancy, we deemed the response to be a CR.
4-6 weeks after completion of CRT
Sang-Hee Cho, MD. PhD
Korea: Food and Drug Administration