RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy is more effective in treating esophageal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of combination chemotherapy in treating patients who are undergoing surgery for esophageal cancer.

Condition	Treatment or Intervention	Phase
stage II esophageal cancer stage III esophageal cancer Adenocarcinoma of the Esophagus	Drug: cisplatin  Drug: epirubicin  Drug: fluorouracil  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: neoadjuvant therapy  Procedure: surgery	Phase III

OBJECTIVES:

• Compare survival and quality of life of patients with resectable adenocarcinoma of the esophagus treated prior to surgery with standard chemotherapy comprising cisplatin and fluorouracil versus prolonged infusional chemotherapy comprising cisplatin, epirubicin, and fluorouracil.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms.

• Arm I (Standard chemotherapy): Patients receive cisplatin IV over 4 hours on days 1-4 and fluorouracil IV continuously on days 1-4. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
• Arm II (Infusional chemotherapy): Patients receive cisplatin IV over 4 hours on day 1, epirubicin IV on day 1, and fluorouracil IV continuously. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo surgery 4-6 weeks after the last dose of fluorouracil in arm I or anytime after the fluorouracil infusion is completed in arm II.

Quality of life is assessed at baseline, immediately before starting the last course of chemotherapy, immediately before surgery, 6 weeks post-operatively, and at 6, 9, 12, 18, and 24 months after randomization.

Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 1,300 patients (650 per treatment arm) will be accrued for this study.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the esophagus or type 1 or 2 tumors of the gastroesophageal junction
• Stage IIB or greater by spiral or multi-slice CT scan and endoscopic ultrasound
• Amenable to primary surgery with curative intent
• No para-aortic/celiac lymphadenopathy greater than 1 cm on CT scan and/or greater than 6 mm on endoscopic ultrasound
• No disease invading the airways, aorta, pericardium, or lung
• No liver, lung, or other distant metastases

PATIENT CHARACTERISTICS: Age:

• Not specified

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 3,000/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• Liver function tests no greater than 1.5 times normal

Renal:

• Glomerular filtration rate greater than 60 mL/min

Cardiovascular:

• Ejection fraction greater than 50% OR
• Normal echocardiograph

Pulmonary:

• FEV1 greater than 1.5 L

Other:

• Not pregnant or nursing
• No prior primary malignancy
• No significant medical condition that would preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• See Disease Characteristics

Study chairs or principal investigators

Derek Alderson, MD,  Study Chair,  Bristol Haematology and Oncology Centre   

Study ID Numbers:  CDR0000069457; MRC-OE05; EU-20204
Record last reviewed:  September 2003
Record first received:  July 8, 2002
ClinicalTrials.gov Identifier:  NCT00041262
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-20