Radiation Therapy and Chemotherapy Before and After Surgery in Treating Patients With Esophageal Cancer
- Conditions
- Esophageal CancerGastric Cancer
- Interventions
- Procedure: conventional surgeryRadiation: radiation therapy
- Registration Number
- NCT00033657
- Lead Sponsor
- Eastern Cooperative Oncology Group
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 97
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cisplatin / Irinotecan / Radiation therapy (Arm A) conventional surgery Days 1 - 35 : Concurrent radiation therapy (RT) and Cisplatin / Irinotecan Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Cisplatin 30 mg/m² days 1, 8, 22, 29. Irinotecan 65 mg/m² days 1, 8, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles Cisplatin / Irinotecan / Radiation therapy (Arm A) radiation therapy Days 1 - 35 : Concurrent radiation therapy (RT) and Cisplatin / Irinotecan Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Cisplatin 30 mg/m² days 1, 8, 22, 29. Irinotecan 65 mg/m² days 1, 8, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles Paclitaxel / Cisplatin / Radiation therapy (Arm B) conventional surgery Days 1 - 35 : Concurrent radiation therapy (RT) and Paclitaxel/Cisplatin Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29. Cisplatin 30 mg/m² days 1, 8, 15, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy. Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles. Paclitaxel / Cisplatin / Radiation therapy (Arm B) radiation therapy Days 1 - 35 : Concurrent radiation therapy (RT) and Paclitaxel/Cisplatin Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29. Cisplatin 30 mg/m² days 1, 8, 15, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy. Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles. Cisplatin / Irinotecan / Radiation therapy (Arm A) cisplatin Days 1 - 35 : Concurrent radiation therapy (RT) and Cisplatin / Irinotecan Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Cisplatin 30 mg/m² days 1, 8, 22, 29. Irinotecan 65 mg/m² days 1, 8, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles Cisplatin / Irinotecan / Radiation therapy (Arm A) irinotecan hydrochloride Days 1 - 35 : Concurrent radiation therapy (RT) and Cisplatin / Irinotecan Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Cisplatin 30 mg/m² days 1, 8, 22, 29. Irinotecan 65 mg/m² days 1, 8, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles Paclitaxel / Cisplatin / Radiation therapy (Arm B) cisplatin Days 1 - 35 : Concurrent radiation therapy (RT) and Paclitaxel/Cisplatin Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29. Cisplatin 30 mg/m² days 1, 8, 15, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy. Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles. Paclitaxel / Cisplatin / Radiation therapy (Arm B) paclitaxel Days 1 - 35 : Concurrent radiation therapy (RT) and Paclitaxel/Cisplatin Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29. Cisplatin 30 mg/m² days 1, 8, 15, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy. Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles.
- Primary Outcome Measures
Name Time Method Pathologic Complete Response Rate 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 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.
- Secondary Outcome Measures
Name Time Method Recurrence-free Survival Time 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 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.
Overall Survival Time 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 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.
Trial Locations
- Locations (23)
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
Ireland Cancer Center
🇺🇸Cleveland, Ohio, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Cancer Institute of New Jersey at Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
CCOP - Sioux Community Cancer Consortium
🇺🇸Sioux Falls, South Dakota, United States
CCOP - Colorado Cancer Research Program, Incorporated
🇺🇸Denver, Colorado, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, 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
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
CCOP - Michigan Cancer Research Consortium
🇺🇸Ann Arbor, Michigan, United States
MetroHealth's Cancer Care Center at MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
St. Joseph's Hospital
🇺🇸Saint Paul, Minnesota, United States
CCOP - Toledo Community Hospital
🇺🇸Toledo, Ohio, United States
CCOP - MainLine Health
🇺🇸Wynnewood, Pennsylvania, United States
CCOP - Scott and White Hospital
🇺🇸Temple, Texas, United States
Lankenau Cancer Center at Lankenau Hospital
🇺🇸Wynnewood, Pennsylvania, United States
CCOP - Marshfield Clinic Research Foundation
🇺🇸Marshfield, Wisconsin, United States
CCOP - Carle Cancer Center
🇺🇸Urbana, Illinois, United States
CCOP - St. Vincent Hospital Cancer Center, Green Bay
🇺🇸Green Bay, Wisconsin, United States
Shands Cancer Center at the University of Florida Health Science Center
🇺🇸Gainesville, Florida, United States
CCOP - Iowa Oncology Research Association
🇺🇸Des Moines, Iowa, United States
University of Wisconsin Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States