Radiation Therapy and Chemotherapy Before and After Surgery in Treating Patients With Esophageal Cancer

OBJECTIVES:

• Compare the pathologic complete response rate in patients with adenocarcinoma of the esophagus or gastroesophageal junction treated with radiotherapy with pre- and post-operative cisplatin plus paclitaxel versus cisplatin plus irinotecan.
• Compare the survival outcome in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the tolerability of these adjuvant chemotherapy regimens after neoadjuvant chemoradiotherapy in these patients.
• Compare time to progression or recurrence in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0 vs. 1) and stage of disease (T2-3, N0, M0 vs. T1-3, N0-1, M0 or M1A). Patients are randomized to 1 of 2 treatment arms.

• Arm A: Patients receive neoadjuvant radiotherapy once daily, 5 days a week, for 5 weeks beginning on day 1 concurrently with neoadjuvant chemotherapy comprising cisplatin IV (Intravenous) over 2-3 hours followed by irinotecan IV over 30-60 minutes once daily on days 1, 8, 22, and 29. Four to six weeks after completion of neoadjuvant chemoradiotherapy, patients undergo surgical resection. A minimum of 4 weeks after resection, patients receive adjuvant chemotherapy comprising cisplatin and irinotecan as above on days 1 and 8. Treatment with adjuvant chemotherapy repeats every 3 weeks for 3 courses.
• Arm B: Patients receive neoadjuvant radiotherapy as in arm A concurrently with neoadjuvant chemotherapy comprising paclitaxel IV (Intravenous) over 1 hour followed by cisplatin IV over 2-3 hours once daily on days 1, 8, 15, 22, and 29. Patients then undergo surgical resection as in arm A. A minimum of 4 weeks after resection, patients receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours followed by cisplatin as above on day 1. Treatment with adjuvant chemotherapy repeats every 3 weeks for 3 courses.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed at 1 month, every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

ACCRUAL: A total of 97 patients (50 on Arm A and 47 on Arm B) were accrued for this study.

Inclusion criteria

• Newly diagnosed adenocarcinoma of the esophagus (20 cm below incisors) or gastroesophageal junction

• Stage T2-3, N0, M0 OR
• Stage T1-3, N0-1, M0 or M1A (celiac nodal metastasis)
• Tumor must be considered surgically resectable (T1-3, but not T4)
• Age>=18 years
• ECOG Performance status 0-1
• Adequate hematopoietic, hepatic, renal functions defined by the following within 4 weeks prior to randomization:
• Granulocyte count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min
• Prior curatively treated malignancy allowed if currently disease-free and survival prognosis is more than 5 years
• Fertile patients must use effective contraception
• Endoscopy with biopsy and dilation allowed

Exclusion criteria

• Tumor extends more than 2 cm into the cardia
• Pregnant or nursing
• Other concurrent illness that would preclude study therapy or surgical resection
• Concurrent filgrastim (G-CSF) during study radiotherapy
• Prior chemotherapy
• Prior radiotherapy
• Prior surgery