Perioperative Vs. Preoperative Chemotherapy With Surgery in the Squamous Carcinoma of Esophagus
|Squamous Carcinoma of Esophagus Esophagus Disorders||Drug: Paclitaxel; Cisplatin; 5-Fluorouracil Drug: Paclitaxel; Cisplatin; 5-Fluorouracil; Capecitabine||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
|Official Title:||Perioperative Versus Preoperative Chemotherapy With Surgery in Patients With Locoregional Squamous Carcinoma of Esophagus|
- Overall survival rate [ Time Frame: 5 years ]
- Progression-free survival [ Time Frame: 3 years ]
- Pathological remission rate [ Time Frame: After 2 cycles of preoperative chemotherapy (2 month) ]
- Resectability rate [ Time Frame: After 2 cycles of preoperative chemotherapy (2 month) ]
- Operative and postoperative complication rate [ Time Frame: Within 30 days after surgery ]
- 30-day mortality [ Time Frame: After date of surgery ]
- Toxicity of preoperative and postoperative chemotherapy
- Rate of local recurrences and metastasis
|Study Start Date:||January 1997|
|Study Completion Date:||January 2010|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
|Active Comparator: Preoperative chemotherapy followed by surgery||
Drug: Paclitaxel; Cisplatin; 5-Fluorouracil
Two preoperative cycles with Paclitaxel 200 mg/m² d1, Cisplatin 60 mg/m² d1, 5-Fluorouracil 700 mg/m² d1-5 repeated every 3 weeks followed by resection
|Active Comparator: Perioperative chemotherapy with surgery||
Drug: Paclitaxel; Cisplatin; 5-Fluorouracil
Two preoperative cycles with Paclitaxel 200 mg/m² d1, Cisplatin 60 mg/m² d1, 5-Fluorouracil 700 mg/m² d1-5 repeated every 3 weeks followed by resectionDrug: Paclitaxel; Cisplatin; 5-Fluorouracil; Capecitabine
Two postoperative cycles with Paclitaxel 200 mg/m²/day d1, Cisplatin 60 mg/m²/day d1, 5-Fluorouracil 700 mg/m²/day d1-5 repeated every 3 weeks Among patients with no responses to preoperative chemotherapy, Capecitabine 625 mg/m² twice-daily dose as alternatives to infused 5-Fluorouracil in the postoperative chemotherapy regimen
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 esophagus, the gastroesophageal 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 are considered to be the most important components to form the cornerstone of this regime.
Paclitaxel is a new and highly active cytotoxic agent. In a randomized phase II study, the dual combination of Paclitaxel and 5-FU seemed to show similar effects as ECF, administered as first line treatment. The triplet combination of Paclitaxel, Cisplatin and 5-FU has significantly superior efficacy than a combination of Cisplatin und 5-FU (Van Cutsem, JCO 2007).
It has been shown that Capecitabine is more active than 5-FU and can replace intravenous 5-FU in the combination with Cisplatin in the treatment of esophageal cancer. Capecitabine therefore is FDA approved for esophageal cancer (Cunningham, ASCO 2006, Kang ASCO 2006).It seems reasonable to optimize perioperative chemotherapy by including this modern chemotherapeutics.
In this study, patients with squamous carcinoma of esophagus and gastroesophageal junction who seem operable with curative intent according to oncological and surgical assessment are treated with 2 preoperative cycles of PCF followed by surgical resection, followed by 2 postoperative cycles of PCF. Among patients with no responses to preoperative chemotherapy, Capecitabine 625 mg/m² twice-daily dose is defined as alternatives to infused 5-Fluorouracil in the postoperative chemotherapy regimen Postoperative chemotherapy will start within 4-6 weeks after the operation. 3 weeks after the end of the last chemotherapy the final investigation (end of study visit) will be done.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01225523
|First Affiliated Hospital of College of Medicine of Xi'an Jiao Tong University|
|Xi'an, Shaanxi, China, 710061|