Radiation Therapy and Paclitaxel, Carboplatin, and Fluorouracil Followed by Esophagectomy in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

OBJECTIVES:

• Determine the pathologic complete response rate in patients with locally advanced cancer of the esophagus or gastroesophageal junction treated with radiotherapy administered concurrently with paclitaxel, carboplatin, and fluorouracil before esophagectomy.
• Determine the tolerability of this regimen in these patients.
• Determine the tumor response rate in patients treated with this regimen.
• Determine the quality of life of patients treated with this regimen.
• Assess the relationship between the presence of genetic polymorphisms in these patients and the toxicity of this regimen.

OUTLINE: This is a multicenter study.

Patients receive carboplatin IV and paclitaxel IV over 3 hours on days 1 and 22 and fluorouracil IV continuously on days 1-42. Beginning on day 1 of chemotherapy, patients undergo radiotherapy to the esophagus 5 days a week for 5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease at 4-8 weeks after completion of radiotherapy undergo esophagectomy and complete dissection of the mediastinal and perigastric lymph nodes. Beginning 8 weeks after surgery, patients who underwent curative resection may receive a maximum of 2 additional courses of paclitaxel and carboplatin in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before chemotherapy on days 1 and 22, and within 2 weeks before surgery.

Patients are followed every 3 months for 4 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed squamous cell carcinoma or adenocarcinoma of the thoracic esophagus (below 20 cm) or gastroesophageal junction

• Surgically resectable disease (T1-3; NX, N0, or N1; M1a)
• T4 tumors that are not unequivocally unresectable allowed
• Celiac lymph node (stations 15-20) involvement allowed
• Must be considered a potential surgical candidate by a thoracic or general surgeon
• No supraclavicular lymph node involvement by palpation, biopsy, or radiograph (greater than 1.5 cm)
• No distant metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

• Patients with ECOG 2 must be considered good candidates for study by treating oncologists

Life expectancy

• At least 12 weeks

Hematopoietic

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

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 3 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No New York Heart Association class III or IV heart disease

Other

• No uncontrolled infection
• No other severe underlying disease that would preclude study participation
• No grade 2 or greater peripheral neuropathy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for esophageal cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to anticipated fields of study radiotherapy

Surgery

• Not specified

Other

• No concurrent diuretics
• No concurrent amifostine