Radiation Therapy and Combination Chemotherapy With or Without Surgery in Treating Patients With Locally Advanced Esophageal Cancer That Can Be Removed By Surgery

OBJECTIVES:

• Compare the survival of patients with locally advanced esophageal cancer treated with neoadjuvant radiotherapy and chemotherapy comprising fluorouracil and cisplatin followed by surgery or radiotherapy and chemotherapy.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to gender, histology (epidermoid vs glandular), response to induction therapy (complete vs partial), and tumor differentiation (little differentiated vs undifferentiated/good vs moderately differentiated).

• Induction therapy: All patients receive induction therapy comprising fluorouracil IV continuously over 24 hours on days 1-5 and cisplatin IV over 1 hour on days 1-5 or on day 2. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo radiotherapy twice daily on days 1-5 and 22-26 or once daily 5 days a week for 4½ weeks. Patients achieving complete or partial response are randomized to 1 of 2 treatment arms.
• Arm I: Patients undergo surgery. Patients may receive 1 course of adjuvant chemotherapy (as in induction therapy) and undergo additional radiotherapy.
• Arm II: Patients receive additional fluoroucacil and cisplatin as in induction therapy. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo additional radiotherapy once daily 5 days a week for 2 weeks.

Quality of life is assessed at baseline, after treatment on arms I or II, and then every 2 months (arm I) or every 6 months (arm II) thereafter.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed epidermoid or glandular cancer of the esophagus meeting the following criteria:

• Tumor volume with or without mediastinal adenopathy, celiac, or subclavicular involvement
• T3, N0-N1 disease
• Tumor extends into fifth stratum by endosonographic scan
• Resectable disease (palliative or curative)
• No cervical tumor
• No T1, T2, or T4 tumors
• No tracheo-esophageal fistula or tracheal invasion
• No gastric cardia cancer by gastroscopy
• No visceral (e.g., lung, bone, brain, liver), ganglion, or clavicular metastases

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Creatinine normal
• WBC ≥ 3,000/mm^3
• Neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Transaminases ≥ 60%
• Bilirubin ≤ 2.0 mg/dL
• No cirrhosis
• DLCO ≥ 1.5 L with or without hypoxemia at rest
• No progressive coronary insufficiency
• Weight loss ≤ 15%
• No other malignancy in the past 2 years
• Must be able to maintain sufficient enteral nutrition (2,000 calories/day)

• Laser photodestruction, dilation, or gastric balloon allowed
• No contraindication to radiotherapy
• No recurring left paralysis

PRIOR CONCURRENT THERAPY:

• No concurrent nephrotoxic or myelotoxic drugs