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

Eastern Cooperative Oncology Group

Status and phase: Completed; Phase 2

Conditions: Gastric Cancer; Esophageal Cancer

Treatments: Drug: cisplatin; Procedure: conventional surgery; Drug: irinotecan hydrochloride; Drug: paclitaxel; Radiation: radiation therapy

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00033657

E1201 (Other Identifier)

CDR0000069309

U10CA021115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 97 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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97 participants in 2 patient groups

Cisplatin / Irinotecan / Radiation therapy (Arm A)

Experimental group

Description:

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

Treatment:

Radiation: radiation therapy

Procedure: conventional surgery

Drug: irinotecan hydrochloride

Drug: cisplatin

Paclitaxel / Cisplatin / Radiation therapy (Arm B)

Experimental group

Description:

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.

Treatment:

Radiation: radiation therapy

Procedure: conventional surgery

Drug: paclitaxel

Drug: cisplatin