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

Eastern Cooperative Oncology Group97 enrolled

Overview

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy before and after surgery may kill more tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of combining radiation therapy with two different chemotherapy regimens before and after surgery in treating patients who have 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.

Interventions

cisplatinDRUG

Days 1 - 35 : Cisplatin 30 mg/m² days 1, 8, 15, 22, 29 Days 63 - 77 : cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles

irinotecan hydrochlorideDRUG

Days 1 - 35 : Irinotecan 65 mg/m² days 1, 8, 22, 29 Days 63 - 77 : irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles

paclitaxelDRUG

Days 1 - 35 : Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29 Days 63 - 77 : paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles

conventional surgeryPROCEDURE

The type of resection (lvor-Lewis, Transhiatal, etc.) was left to the discretion of the operating surgeon. One lymph node dissection was required.

radiation therapyRADIATION

The total dose to the prescription point was 4500 cGy given in 25 fractions. The patient was treated with one fraction per day with all fields treated per day. 180 cGy was delivered to the isocenter. If the dose to the supraclavicular fossa (SCF) was less than 4500 cGy, a localized photon or electron boost was allowed in order to increase the SCF dose to 4500 cGy, specified at 3 cm depth from the anterior skin surface.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (23)

CCOP - Colorado Cancer Research Program, Incorporated

Denver, Colorado, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Shands Cancer Center at the University of Florida Health Science Center

Gainesville, Florida, United States

Veterans Affairs Medical Center - Lakeside Chicago

Chicago, Illinois, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

...and 13 more locations

Outcomes

Primary Outcomes

Pathologic Complete Response Rate

A patient would have achieved a pathologic complete response if no histopathological evidence of residual tumor is found in the resected esophageal specimen and nodal tissue.

Time frame: approximately 1 month after completing all treatments, then every 3 months up to 2 years, every 6 months from 2-5 years of study entry and annually 6-10 years from study entry

Secondary Outcomes

Overall Survival Time

Survival was measured from the date of randomization onto study to death from any cause.Patients who were still alive at the end of the study were censored at the last date of known alive. Median survival time was calculated in the 81 eligible and treated patients.

Time frame: Approximately 1 month after completing all treatments, then every 3 months up to 2 years, every 6 months from 2-5 years of study entry and annually 6-10 years from study entry

Recurrence-free Survival Time

Recurrence-free survival is measured from the date of complete response to recurrence of the cancer. Patients without recurrence were censored at the last date of known recurrence-free. Median recurrence-free survival time was calculated in the eligible and treated patients.