Radiation Therapy and Paclitaxel, Carboplatin, and Fluorouracil Followed by Esophagectomy in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Gastric Cancer; Esophageal Cancer

Treatments: Radiation: radiation therapy; Drug: carboplatin; Procedure: conventional surgery; Drug: fluorouracil; Drug: paclitaxel

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00022139

NCCTG-N0044

NCI-2012-02394 (Registry Identifier)

CDR0000068789 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy and giving them before surgery may shrink the tumor so that it can be removed during surgery.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with combination chemotherapy followed by esophagectomy works in treating patients with locally advanced cancer of the esophagus or gastroesophageal junction.

Full description

OBJECTIVES:

• Determine the pathologic complete response rate in patients with locally advanced cancer of the esophagus or gastroesophageal junction treated with radiotherapy administered concurrently with paclitaxel, carboplatin, and fluorouracil before esophagectomy.
• Determine the tolerability of this regimen in these patients.
• Determine the tumor response rate in patients treated with this regimen.
• Determine the quality of life of patients treated with this regimen.
• Assess the relationship between the presence of genetic polymorphisms in these patients and the toxicity of this regimen.

OUTLINE: This is a multicenter study.

Patients receive carboplatin IV and paclitaxel IV over 3 hours on days 1 and 22 and fluorouracil IV continuously on days 1-42. Beginning on day 1 of chemotherapy, patients undergo radiotherapy to the esophagus 5 days a week for 5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease at 4-8 weeks after completion of radiotherapy undergo esophagectomy and complete dissection of the mediastinal and perigastric lymph nodes. Beginning 8 weeks after surgery, patients who underwent curative resection may receive a maximum of 2 additional courses of paclitaxel and carboplatin in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before chemotherapy on days 1 and 22, and within 2 weeks before surgery.

Patients are followed every 3 months for 4 years.

Enrollment: 56 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed squamous cell carcinoma or adenocarcinoma of the thoracic esophagus (below 20 cm) or gastroesophageal junction

  • Surgically resectable disease (T1-3; NX, N0, or N1; M1a)
  • T4 tumors that are not unequivocally unresectable allowed
  • Celiac lymph node (stations 15-20) involvement allowed

• Must be considered a potential surgical candidate by a thoracic or general surgeon

• No supraclavicular lymph node involvement by palpation, biopsy, or radiograph (greater than 1.5 cm)

• No distant metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

  • Patients with ECOG 2 must be considered good candidates for study by treating oncologists

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 3 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No New York Heart Association class III or IV heart disease

Other

• No uncontrolled infection
• No other severe underlying disease that would preclude study participation
• No grade 2 or greater peripheral neuropathy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for esophageal cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to anticipated fields of study radiotherapy

Surgery

• Not specified

Other

• No concurrent diuretics
• No concurrent amifostine

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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56 participants in 1 patient group

carboplatin + paclitaxel + fluorouracil + radiation + surgery

Experimental group

Description:

Patients receive carboplatin IV and paclitaxel IV over 3 hours on days 1 and 22 and fluorouracil IV continuously on days 1-42. Beginning on day 1 of chemotherapy, patients undergo radiotherapy to the esophagus 5 days a week for 5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease at 4-8 weeks after completion of radiotherapy undergo esophagectomy and complete dissection of the mediastinal and perigastric lymph nodes. Beginning 8 weeks after surgery, patients who underwent curative resection may receive a maximum of 2 additional courses of paclitaxel and carboplatin in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, before chemotherapy on days 1 and 22, and within 2 weeks before surgery. Patients are followed every 3 months for 4 years.

Treatment:

Drug: fluorouracil

Procedure: conventional surgery

Radiation: radiation therapy

Drug: paclitaxel

Drug: carboplatin