Chemotherapy, Radiation Therapy, and Cetuximab Followed by Surgery, Docetaxel, and Cetuximab in Treating Patients With Esophageal Cancer or Gastroesophageal Junction Cancer

• Toxicity and safety [ Designated as safety issue: Yes ]
• Time to progression, time to recurrence, and overall survival [ Designated as safety issue: No ]

• Toxicity and safety
• Time to progression, time to recurrence, and overall survival

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving docetaxel and cetuximab after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving chemotherapy and radiation therapy together with cetuximab followed by surgery, docetaxel and cetuximab works in treating patients with esophageal cancer or gastroesophageal junction cancer.

OBJECTIVES:

Primary

• To determine the pathologic complete response rate in patients with resectable adenocarcinoma of the esophagus or gastroesophageal junction treated with neoadjuvant chemoradiotherapy comprising oxaliplatin, fluorouracil, and radiation therapy combined with cetuximab.

Secondary

• To evaluate the safety of this regimen in these patients.
• To evaluate the safety and tolerability of adjuvant therapy comprising cetuximab and docetaxel in these patients.

OUTLINE: This is a multicenter study.

• Neoadjuvant chemoradiotherapy and cetuximab: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29, cetuximab IV over 1-2 hours on days 1, 8, 15, 22, and 29, and fluorouracil IV continuously over 24 hours on days 1-35. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients then proceed to surgery.
• Surgery: Patients undergo surgical resection within 4-8 weeks after completion of neoadjuvant chemoradiotherapy and cetuximab. Patients with an R0 or R1 resection proceed to adjuvant therapy. Patients whose tumors have not been completely resected or who have metastatic disease discontinue protocol therapy and receive further therapy at the discretion of the treating physician.
• Adjuvant therapy: Within 4-8 weeks after surgery, patients receive docetaxel IV over 1 hour on days 1, 8, 15, 22, and 29 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, and then every 6 months for 3-5 years.

• Biological: cetuximab
• Drug: docetaxel
• Drug: fluorouracil
• Drug: oxaliplatin
• Procedure: adjuvant therapy
• Procedure: conventional surgery
• Procedure: neoadjuvant therapy
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction meeting the following criteria:

  • Newly diagnosed disease
  • Tumor is ≥ 20 cm below the incisors
  • Tumor extending ≤ 2 cm into cardia

  • Tumors must be considered surgically resectable (T1-3)

    • No T4 tumors

• Stage T2 N0 M0, T3 N0 M0, T1-3 N+ M0, or T1-3 N0-1 M1a by imaging studies (and biopsy when appropriate) performed within the past 4 weeks

  • M1a disease (i.e., celiac nodal metastasis) is allowed provided other eligibility criteria are met

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Granulocytes > 1,000/ mm³
• Platelets > 100,000/mm³
• Creatinine normal or creatinine clearance > 60 mL/min
• Total serum bilirubin < 1.5 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• History of a curatively treated malignancy from which the patient has been disease-free for ≥ 2 years and has a survival prognosis of > 5 years
• Patients with a history of breast cancer remaining on hormonal treatment > 5 years are eligible
• No prior severe infusion reaction to a monoclonal antibody
• No infection
• No hypertension
• No uncontrolled diabetes
• No intercurrent illness that would likely interfere with protocol therapy or prevent surgical resection

• None of the following within the past 6 months:

  • New York Heart Association class III-IV congestive heart failure
  • Cerebrovascular accident or transient ischemic attack
  • Unstable angina or myocardial infarction

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, radiotherapy, or surgery

  • Endoscopy with biopsy and dilation is allowed
• No prior therapy specifically and directly targeting the EGFR pathway