Combination Chemotherapy Followed By Chemoradiotherapy, With or Without Surgery, in Treating Patients With Resectable Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 2

Conditions: Esophageal Cancer

Treatments: Radiation: radiation therapy; Procedure: conventional surgery; Drug: paclitaxel; Drug: cisplatin; Drug: fluorouracil; Biological: pegfilgrastim; Biological: filgrastim

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT00069953

CDR0000306455

RTOG-0246

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy such as paclitaxel, fluorouracil, and cisplatin use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells

PURPOSE: This phase II trial is studying how well combination chemotherapy followed by chemoradiotherapy, with or without surgery, works in treating patients with resectable locally advanced cancer of the esophagus or gastroesophageal junction.

Full description

OBJECTIVES:

• Determine the feasibility of treatment with paclitaxel, cisplatin, and fluorouracil followed by chemoradiotherapy and possible surgical salvage in patients with resectable locally advanced carcinoma of the esophagus or gastroesophageal junction.
• Determine the overall and disease-free survival of patients treated with this regimen.
• Determine the treatment-related toxicity of this regimen in these patients.
• Determine the tolerance to surgical salvage in patients treated with this regimen.
• Determine the morbidity and mortality of surgical salvage in patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive fluorouracil (5-FU) IV continuously over 96 hours beginning on days 1 and 29; cisplatin IV over 1 hour on days 1-5 and 29-33; paclitaxel IV over 2 hours on days 1 and 29; and pegfilgrastim subcutaneously (SC) on days 6 and 34 OR filgrastim (G-CSF) SC on days 6-15 and 34-42. Treatment continues in the absence of unacceptable toxicity.
• Chemoradiotherapy: Patients receive cisplatin IV over 1 hour on days 57-61 and 5-FU IV continuously on days 57-61, 64-68, 71-75, 78-82, 85-89, and 92-96. Patients concurrently undergo external beam radiotherapy on days 57-61, 64-68, 71-75, 78-82, 85-89, and 92-96.

Patients with residual or recurrent esophageal disease 4-6 weeks after completion of chemoradiotherapy may undergo salvage esophagectomy.

Patients are followed periodically.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study within 18 months.

Enrollment: 43 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction

  • Primary (non-recurrent) disease
  • Amenable to resection
  • Stage greater than T1, N0 by endoscopic ultrasound
  • Must be entirely confined to the esophagus or gastroesophageal junction and periesophageal soft tissue
  • Tumor may not extend more than 2 cm into the stomach

• No multiple primary carcinomas of the esophagus

• No cervical esophageal carcinoma or tumors less than 5 cm from cricopharyngeus

• No evidence of disseminated cancer

  • Suggestion of liver metastases by positron emission tomography must be proven negative by biopsy or other imaging studies
  • Palpable supraclavicular nodes must be negative for cancer by biopsy

• Bronchoscopy required for lesions less than 26 cm from the incisors to exclude tracheoesophageal fistula or invasion

• No celiac adenopathy greater than 2 cm

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 150,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic

• Not specified

Renal

• Creatinine no greater than 1.5 mg/dL AND/OR
• Creatinine clearance at least 65 mL/min
• Calcium no greater than 11 mg/dL

Cardiovascular

• No uncontrolled heart disease
• No uncontrolled hypertension

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to comprehend study requirements and considered likely to comply with study parameters
• No other malignancy within the past 5 years except curable nonmelanoma skin cancer or carcinoma in situ of the cervix
• No uncontrolled diabetes
• No hypersensitivity to E. coli-derived products

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 5 years since prior systemic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior chest or upper abdomen radiotherapy

Surgery

• No prior esophageal or gastric surgery

Other

• No concurrent photodynamic therapy
• No other concurrent investigational agents for esophageal carcinoma

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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43 participants in 1 patient group

ChemoRT and selective surgery

Experimental group

Description:

Induction therapy of fluorouracil, cisplatin, paclitaxel, and pegfilgrastim OR filgrastim, then chemoradiotherapy of concurrent cisplatin and fluorouracil with external beam radiotherapy (RT), followed by selective salvage therapy.

Treatment:

Biological: pegfilgrastim

Biological: filgrastim

Drug: fluorouracil

Drug: cisplatin

Radiation: radiation therapy

Procedure: conventional surgery

Drug: paclitaxel