Fluorouracil, Cisplatin, Cetuximab, and Radiation Therapy in Treating Patients With Esophageal Cancer That Can Be Removed by Surgery

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of fluorouracil and cisplatin when administered with cetuximab concurrently with esophageal radiotherapy. (Phase I)
• To determine the complete histological response rate (after surgical resection). (Phase II)

Secondary

• To determine progression-free survival and overall survival. (Phase II)
• To determine the rate of resection with negative margins (R0). (Phase II)
• To determine the overall tolerance to neoadjuvant therapy. (Phase II)
• To determine the postoperative morbidity and mortality. (Phase II)

OUTLINE: This is a multicenter study. This is a dose-escalation study of cisplatin and fluorouracil.

Patients receive cetuximab IV over 2 hours on day -7, then IV over 1 hour on days 1, 8, 15, 22, and 29. Patients also receive cisplatin IV over 1 hour on day 1 or 2 and fluorouracil IV continuously on days 1-4, 8-11, 15-18, 22-25, and 29-32. Patients undergo radiotherapy 5 days a week for 5 weeks, beginning on day 1 of chemotherapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients undergo surgery within 6-8 weeks after completion of chemoradiotherapy.

After completion of study therapy, patients are followed at 1 month, every 4 months for 2 years, and then every 6 months for 2 years.

DISEASE CHARACTERISTICS:

Inclusion criteria

• Histologically confirmed epidermoid or glandular carcinoma of the thoracic esophagus

• Invasive disease
• Only Siewert type I gastroesophageal carcinoma allowed
• Resectable disease

• T1N+, T2N0, T2N+, T3N0, or T3N+ (stage II or III)
• No visceral metastases or mediastinal extensions compromising resectability

Exclusion criteria

• Inoperable disease
• Invasion of the tracheo-bronchial tree
• Recurring esophageal paralysis
• Esopho-tracheal fistula
• Cervical esophageal carcinoma (< 19 cm above the dental arches)
• Multifocal esophageal carcinoma
• Superficial esophageal carcinoma (T1N0)
• Esophageal carcinoma in the lymph nodes that cannot be included in the radiotherapy field or cannot be completely surgically resected
• Proven metastatic disease

PATIENT CHARACTERISTICS:

Inclusion criteria

• WHO performance status 0-1
• Weight loss < 15%
• Absolute neutrophil count ≥ 1,500/mm3
• Platelet count ≥ 100,000/mm3
• Creatinine ≤ 1.25 times upper limit of normal
• PTT ≥ 80%
• Albumin ≥ 35 g/L
• FEV1 > 1 L
• Not pregnant or nursing
• Fertile patients of must use effective contraception

Exclusion criteria

• Known liver cirrhosis
• Renal insufficiency
• Respiratory insufficiency (i.e., severe dyspnea at rest or oxygen dependence)
• Progressive coronary insufficiency
• Myocardial infarction in the past 6 months
• Legally incapacitated
• Impossible to receive study therapy due to geographical, social, or psychological reasons
• Noncompliant within constraints of the study
• Hematologic malignancy or other cancer except carcinoma in situ of the uterine cervix, treated nonmelanoma skin cancer, or intramucous disease treated within the past 3 years

PRIOR CONCURRENT THERAPY:

Exclusion criteria

• Prior anticancer chemotherapy or radiotherapy
• Treatment with endoprosthesis
• Surgery (esophagectomy) planned without thoracotomy