Surgery With or Without Radiation Therapy and Chemotherapy in Treating Patients With Esophageal Cancer

Federation Francophone de Cancerologie Digestive

Status and phase: Completed; Phase 3

Conditions: Esophageal Cancer

Treatments: Radiation: radiation therapy; Drug: cisplatin; Procedure: neoadjuvant therapy; Drug: fluorouracil; Procedure: conventional surgery

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT00047112

EORTC-22001

FRE-FNCLCC-FFCD-9901

FFCD-9901

EORTC-40001

SFRO-FFCD-9901

CDR0000257600

FRE-GERCOR-FFCD-9901

EU-20215

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy with radiation therapy before surgery may shrink the tumor so it can be removed during surgery. It is not yet known if surgery is more effective with or without radiation therapy and chemotherapy in treating esophageal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without radiation therapy and chemotherapy in treating patients who have esophageal cancer.

Full description

OBJECTIVES:

• Compare the overall survival of patients with resectable thoracic esophageal cancer treated with neoadjuvant radio-chemotherapy and surgery versus surgery alone.
• Compare the disease-free survival of patients treated with these regimens.
• Compare the surgical mortality and morbidity of patients treated with these regimens.
• Compare the resectability of patients treated with these regimens.
• Determine the validation of new prognostic factors for survival of these patients and/or the efficacy of this neoadjuvant treatment.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to histology (epidermoid carcinoma vs adenocarcinoma vs undifferentiated carcinoma), stage (I vs IIA vs IIB), tumor location (above the carina vs below the carina), and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy daily 5 days a week for 5 weeks. Patients receive fluorouracil IV continuously on days 1-4 and 29-32 and cisplatin IV on days 1 or 2 and 29 or 30 (or a lower dose on days 1-5 and 29-33). Within 4-8 weeks after completion of radio-chemotherapy, patients undergo surgical resection.
• Arm II: Patients undergo surgical resection. Patients are followed every 4 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 380 patients (190 per treatment arm) will be accrued for this study within 3 years.

Enrollment: 195 patients

Sex: All

Ages: Under 74 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of stage I or II thoracic esophageal cancer

  • Tumor no greater than 3 cm with no invasion of mediastinal structures with or without extension to the lymph nodes (T1-2, N0-1, M0) OR
  • Tumor greater than 3 cm with no invasion of mediastinal structures and no adenopathy greater than 1 cm (T3, N0, M0)
  • Epidermoid carcinoma or adenocarcinoma

• Previously untreated

• Deemed resectable with curative intent

• No carcinoma in situ

• No small cell anaplastic carcinoma (i.e., chromogranin negative)

• No small cell neuroendocrine carcinoma (i.e., chromogranin positive)

• No multifocal esophageal carcinoma (i.e., 2 or more distinct lesions 5 or more cm apart)

• No involvement of the pharyngoesophageal junction and the first 4 cm of the esophagus (i.e., where the proximal edge of the tumor is less than 19 cm from the dental arch)

• No evidence of extension to the tracheobronchial tree at endoscopy, ultrasound, or CT scan (simple compression allowed)

• No signs of mediastinal involvement on CT scan

• No palpable subclavicular lymph nodes or involvement after cytology needle aspiration

• No lymph nodes from the origin of the celiac greater than 1 cm on CT scan

  • Perigastric lymph nodes far from the celiac trunk and deemed resectable allowed unless tumor is more than 30 mm on CT scan

PATIENT CHARACTERISTICS:

Age

• Under 75

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• SGOT/SGPT ratio no greater than 1
• Albumin at least 35 g/L
• Total protein greater than 80%
• No liver cirrhosis with previous failure
• No ascites
• No jaundice
• No rupture of varicose esophageal veins
• No presence of varicose esophageal veins

Renal

• Creatinine no greater than 1.25 times normal

Cardiovascular

• Arterial O_2 greater than 60 mm Hg
• Arterial CO_2 no greater than 45 mm Hg
• No myocardial infarction within the past 6 months
• No progressive coronary artery disease grade 2 or greater
• No recent left ventricular failure
• No arterial disease stage II-IV

Pulmonary

• FEV_1 greater than 1 L/sec

Other

• Able to receive either study treatment
• No recurrent paralysis
• No weight loss greater than 10% from baseline
• No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• Not pregnant
• Fertile patients must use effective contraception during and for 3 months after completion of chemotherapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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195 participants in 2 patient groups

CHIMIORADIOTHERAPIE SUIVIE DE CHIRURGIE

Experimental group

Description:

CHIMIORADIOTHERAPIE SUIVIE DE CHIRURGIE

Treatment:

Drug: fluorouracil

Procedure: conventional surgery

Radiation: radiation therapy

Drug: cisplatin

Procedure: neoadjuvant therapy

CHIRURGIE SEULE

Active Comparator group

Description:

CHIRURGIE SEULE

Treatment:

Procedure: conventional surgery