Multicenter, Open Lable Phase II Study to Evaluate the Safety and Efficacy of a Perioperative Chemotherapy With Docetaxel, Cisplatin and Capecitabine in Patients With Gastric Adenocarcinoma, Adenocarcinoma of the Gastro-esophageal Junction or the Distal Esophagus
Perioperative chemotherapy has been shown to significantly improve the R0 resection rate,
the disease free survival and the overall survival in patients with adenocarcinoma of the
distal esophagus, the gastro-esophageal junction and the stomach. Therefore perioperative
chemotherapy is the new therapeutic standard (Cunningham NEJM 2006, MRC, Lancet 2002, Boige
ASCO 2007). The best evaluated regime is the combination of Epirubicin, Cisplatin and 5-FU
(ECF) (Cunningham, NEJM 2007). Cisplatin and 5-FU seem to be the most important components
forming the backbone of this regime (Boige ASCO 2007).
Docetaxel is a new and highly active agent in gastric cancer. In a randomized phase II study
the dual combination of Docetaxel and 5-FU seemed to show similar activity as ECF,
administered as first line palliative treatment (Thuss-Patience, JCO, 2005). The three drug
combination Docetaxel, Cisplatin, 5-FU has significantly superior efficacy than a
combination of Cisplatin und 5-FU, superior quality of life and significantly superior
overall survival (Van Cutsem, JCO 2007).
It has been shown that Capecitabine the oral prodrug of 5-FU is similarly active as 5-FU and
can replace intravenous 5-FU in combination with Cisplatin in the treatment of gastric
cancer. Capecitabine therefore is FDA approved for gastric cancer (Cunningham, ASCO 2006,
Kang ASCO 2006).
It seems reasonable to optimize perioperative chemotherapy by including modern
chemotherapeutics. The old standard ECF may be improved by integrating Docetaxel und
Capecitabine. By adding Docetaxel to the Cisplatin / flouropyrimidin backbone the efficacy
of the regime may be improved. The replacement of 5-FU by Capecitabine may improve patients´
convenience and possibly effectiveness of the combination. Therefore the 3 drug combination
of Docetaxel, Cisplatin, Capecitabin (DCX) seems to be a highly promising regime regarding
effectiveness and convenience.
In this study patients with adenocarcinoma of the stomach, gastro-esophageal junction or the
distal esophagus who seem operable with curative intent according to oncological and
surgical assessment are treated with 3 preoperative cycles of DCX followed by surgical
resection, followed by 3 postoperative cycles of DCX.
The first application of study medication has to be within 21 days of tumour assessment.
There will be 3 preoperative cycles every 3 weeks. The experimental perioperative regime
evaluated in this study will be Docetaxel/Cisplatin/Capecitabine DCX (75/ 60/ 1875
mg/m2).The operation will be performed 3 to 6 weeks after the end of the third preoperative
chemotherapy cycle (counted from day 21 of cycle 3).
Postoperative chemotherapy will start within 6 - 12 weeks after the operation. 3 weeks after
the end of the last chemotherapy the final investigation (end of study visit) will be done.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
After 3 cycles of preoperative chemotherapy (3 month)
Peter Thuss-Patience, Dr. med.
Charite University, Berlin, Germany
Germany: Federal Institute for Drugs and Medical Devices