Title
Surgery With or Without Chemotherapy and Radiation Therapy in Treating Patients With Cancer of the Esophagus
A Prospective Randomized Phase III Trial Comparing Trimodality Therapy (Cisplatin, 5-FU, Radiotherapy, and Surgery) to Surgery Alone for Esophageal Cancer
Phase
Phase 3Lead Sponsor
National Cancer Institute (NCI)Study Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Esophageal CancerIntervention/Treatment
fluorouracil cisplatin ...Study Participants
56RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether surgery is more effective with or without chemotherapy and radiation therapy for cancer of the esophagus.
PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without combination chemotherapy and radiation therapy in treating patients who have cancer of the esophagus that can be surgically removed.
OBJECTIVES: I. Compare overall five-year survival rates and treatment failures in patients receiving neoadjuvant cisplatin (CDDP) plus fluorouracil (5-FU) with concomitant radiotherapy followed by surgical resection versus patients receiving surgery alone. II. Assess and compare the toxicities of each approach. III. Compare the incidence and pattern of local (gastric or esophageal bed or regional lymph nodes) and distant (supraclavicular lymph node, liver, peritoneal carcinomatosis, or lung, brain, etc.) recurrence. IV. Evaluate the prognostic ability of noninvasive and minimally invasive pretreatment staging with regard to survival and recurrence. V. Evaluate the ability of preresection adjuvant chemotherapy with concomitant radiation therapy to render tumors to lower stages. VI. Evaluate the impact of lymph nodes on survival and recurrence.
OUTLINE: This a two arm, randomized study. Patients are stratified by: cell type of cancer (squamous cell vs adenocarcinoma); lymph nodes (positive vs negative); and stage (invasive vs noninvasive). Patients in arm I undergo chemotherapy and radiotherapy within 24 hours of each other. Chemotherapy consists of cisplatin (CDDP) by bolus IV infusion over 30 minutes on day 1 and again on day 29. Fluorouracil (5-FU) is administered by continuous IV infusion for 4 days (on days 1-4 and 29-32) after completion of cisplatin. Radiotherapy is administered on days 1-5, 8-12, 15-19, 22-26, and 29-33, with a boost on days 36-38. If there is no disease progression or unresectable disease, surgery is performed within 3-8 weeks following completion of therapy. Patients in arm II undergo surgery alone no later than 6 weeks postrandomization. Patients are followed at least every 3 months for two years, then every 6 months for the next two years, and annually thereafter.
Patients with histologically documented untreated squamous cell carcinoma or adenocarcinoma of the thoracic esophagus (below 20 cm) or gastro-esophageal junction and with less than 2 cm distal spread into the gastric cardia were eligible. No evidence of distant metastatic disease by history and physical examination Upper endoscopy with biopsy, computed tomography (CT) of the chest and upper abdomen, and pulmonary function studies are required. Bone scan is required for alkaline phosphatase more than 3X the institutional normal value. Bronchoscopy is required if the primary tumor was adjacent to the trachea or left main stem bronchus. Patients are required to have: granulocyte counts ≥1,800/mL platelet count ≥ 100,000/mL creatinine clearance ≥ 50 mL/min Esophageal ultrasound (EUS) and preresection staging by thoracoscopy (ts) and laparoscopy/minilaparotomy (ls), including biopsy of celiac axis and lesser curvature are recommended Tumors must be considered surgically resectable (T1-3, NX), including regional thoracic lymph node (N1) metastases. Patients with supraclavicular lymph nodes measuring ≤ 1.5 cm by CT (not palpable) are eligible. Patients with lymph node metastases to levels 15 to 20 (predominantly celiac axis and paracardial nodes) ≤1.5 cm by CT. Patients may not have previously received chemotherapy or radiation therapy for this tumor or any radiation therapy that would overlap the radiation fields required for this malignancy. Patients with previous malignancies are eligible if more than 5 years had elapsed from diagnosis without evidence of tumor recurrence. There can be no other serious illness that would limit survival to less than 2 years, or psychiatric condition that would prevent compliance with treatment or informed consent. Patients with uncontrolled or severe cardio- vascular disease,pulmonary disease, oractive infections are excluded. Pregnant patients are excluded. Informed consent is required for all patients.
