Surgery With or Without Combination Chemotherapy in Treating Patients With Cancer of the Esophagus

Unicancer

Status and phase: Completed; Phase 3

Conditions: Gastric Cancer; Esophageal Cancer

Treatments: Drug: fluorouracil; Drug: cisplatin; Procedure: conventional surgery; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00002883

EU-96018

CDR0000065190

FRE-FNCLCC-94012

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. It is not known whether combining chemotherapy with surgery is more effective than surgery alone.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without combination chemotherapy in treating patients with cancer of the esophagus.

Full description

OBJECTIVES:

• Compare survival in patients with operable adenocarcinoma of the lower third of the esophagus or the cardia treated with fluorouracil/cisplatin vs. no chemotherapy prior to surgical resection.
• Assess whether neoadjuvant fluorouracil/cisplatin increases tumor resectability.

OUTLINE: This study is randomized for neoadjuvant chemotherapy. Patients are stratified by performance status, tumor location, and randomizing center.

Patients randomized to no neoadjuvant chemotherapy undergo resection of the tumor with adequate margins and resection of regional lymph nodes (R2 with at least 8 nodal groups recommended).

Patients randomized to neoadjuvant chemotherapy receive fluorouracil and cisplatin at 3-4 week intervals; fluorouracil is given by continuous intravenous infusion for 5 days and cisplatin is given on the first 2 days of fluorouracil administration. Tumor response is assessed after 2 courses; responding patients with no serious toxicity receive a third course. Surgery, as above, is initiated 4-6 weeks after the second or third course of chemotherapy. Upon recovery (within 3-6 weeks), patients who responded to neoadjuvant chemotherapy receive 3-4 additional courses of postoperative chemotherapy (maximum total of 6 courses). Patients whose best response was stable disease are assessed for postoperative radiotherapy.

Patients on either arm with positive resection margins, positive lymph nodes, or equivocal complete resection are referred for postoperative radiotherapy. Further therapy for patients with incomplete resection is at the discretion of the physician.

Patients are followed every 3-4 months for at least 5 years.

PROJECTED ACCRUAL: A total of 250 patients will be entered.

Enrollment: 250 estimated patients

Sex: All

Ages: Under 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Adenocarcinoma of the lower third of the esophagus or the cardia for which complete resection is feasible

  • Extension to the cardia allowed

  • Cancer of the cardia with extension to the esophagus or stomach allowed

    • No in situ cancer of the cardia

  • No distant metastases

PATIENT CHARACTERISTICS:

Age:

• Not over 75

Performance status:

• WHO 0 or 1

Hematopoietic:

• WBC at least 4,000
• Polymorphonuclear lymphocytes greater than 2,000
• Platelets at least 100,000

Hepatic:

• Not specified

Renal:

• Creatinine less than 1.3 mg/dL (120 micromoles/L)

Cardiovascular:

• No prior myocardial infarction
• No other cardiac contraindication to surgery

Pulmonary:

• No respiratory contraindication to surgery

Other:

• No second malignancy except:
• Basal cell carcinoma of the skin
• Adequately treated in situ carcinoma of the uterine cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for tumors of the cardia

Endocrine therapy

• No prior radiotherapy for tumors of the cardia

Radiotherapy

• Not specified

Surgery

• Not specified