Perioperative Vs. Preoperative Chemotherapy With Surgery in the Squamous Carcinoma of Esophagus

Health Science Center of Xi'an Jiaotong University

Status and phase

Completed

Phase 1

Conditions

Squamous Carcinoma of Esophagus

Esophagus Disorders

Treatments

Drug: Paclitaxel; Cisplatin; 5-Fluorouracil

Drug: Paclitaxel; Cisplatin; 5-Fluorouracil; Capecitabine

Study type

Interventional

Funder types

Other

Identifiers

NCT01225523

ZY-01

Details and patient eligibility

About

To assess whether or not a perioperative therapy with surgery can improve the outcomes among patients with potentially curable squamous carcinoma of esophagus as compared to a preoperative chemotherapy followed by surgery

Full description

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.

Enrollment

350 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Signed informed consent
histologically confirmed esophageal cancer (squamous carcinoma) measurable, non-metastatic disease
no previous cancer therapy (chemotherapy, radiotherapy or resection)
life expectancy > 3 months
age > 18 years
WHO Status ≤ 1
Intended curative resection according to evaluation of an experienced surgeon
Negative pregnancy blood test at screening but not earlier than 72 hours prior to start of chemotherapy for women with child bearing potential
Adequate haematologic function and liver and renal function: neutrophils > 1.5×109/L; thrombocytes > 100×109/L; haemoglobin > 10 g/dl, creatinine clearance > 60 ml/min (calculated according to Cockroft and Gault), total bilirubin < 1.0×UNL; AST and ALT < 1.5×UNL, AP < 2.5×UNL
Complete staging within 3 weeks prior to start of treatment (CT-scan of thorax and abdomen, endosonography, gastroscopy)
Ability to keep appointments and follow the study protocol
By CT-scan, endoscopy or endosonography measurable or evaluable disease

Exclusion criteria

Former therapy of cancer (operation, chemo- or radiotherapy)
Diagnosis of another cancer in the last 5 years prior to study entry which has not been cured by operation only (exception in-situ-carcinoma of the cervix or cured non-melanomatose skin cancer)
Known contraindication to the planned chemotherapeutics
Presence of distant metastases
Anamnestic known serious disease or other concomitant diseases that affect participation in this study, such as:

oInstable cardiac disease: symptomatic heart failure, symptomatic coronary artery disease, ventricular cardiac arrhythmia not well controlled with medication, myocardial infarction or resuscitation within 6 month before study oActive infection necessitating systemic therapy or uncontrolled infection oInterstitial lung diseases (for example: pneumonitis or fibrosis of the lung) and indication for interstitial lung disease in chest x-ray or CT-scan respectively oActive inflammatory bowel disease or other bowel diseases which provoke chronic diarrhea (defined as > 4 bowel movements per day) oNeurological or psychiatric disease including dementia, epilepsy or untreated, symptomatic brain metastases oLimited hearing ability

Presence of upper GI obstruction, leading to inability to swallow ground tablets
Presence of acute or chronic systemic infection
Presence of a bowel obstruction within the last 30 days
Pregnant or lactating women or women with child bearing potential and men without adequate contraception (high effective contraception, defined as Pearl Index < 1) like birth control pill, hormone spiral, hormone implant, transdermal patch, a combination of two barrier methods (condom and diaphragm), realized sterilization or sexual abstinence during the study and at least for 3 months after the last infusion
Any other situation which may lead to an unacceptable high risk for the patient, when he participates in the study
Parallel treatment in another clinical study or prior participation in this study
Treatment with any other therapy against the tumor or any parallel radiation
Symptomatic peripheral neuropathy NCI-CTCAE degree > 2
Intolerance to the study medication
Detention in a psychiatric unit or imprisonment