Epirubicin, Oxaliplatin and Fluorouracil (EOF) in Cancer of the Esophagus, Gastroesophageal Junction, or Stomach
Condition: Esophageal Cancer; Gastric Cancer
MeSH terms: Stomach Neoplasms; Esophageal Neoplasms
Intervention: cisplatin; epirubicin hydrochloride; fluorouracil; oxaliplatin; adjuvant therapy; neoadjuvant therapy
Intervention description: 20 mg/m2/day IV continuous infusion over 24 hours for 96 total hours.; 50 mg/m2 IV bolus; 200 mg/m2/day will be given as a continuous intravenous infusion for all 9 weeks, beginning on day 1.; 130 mg/m2 IV infusion over 2 hours; Between 6-10 weeks after surgery patients will begin postoperative chemoradiotherapy. Daily radiation therapy fractions of 180-200 cGy will be given to the esophago-gastric bed and draining lymphatic regions to a total dose of 50-55 Gy (60 Gy in the event of an R1 or R2 resection). Concurrent with this radiation, two cycles of chemotherapy will be given, during the first and fourth weeks of the radiation; Three weeks after discontinuing the fluorouracil (12 weeks after study entry) patients will be fully restaged to assess for a clinical response, and to ensure that there is no contraindication to surgical resection, which will be scheduled for approximately one week later (13 weeks after study entry).
Surgery will consist of a transthoracic esophagogastrectomy or a total gastrectomy with Roux-en-Y esophagojejunostomy depending on the location and extent of the tumor at surgery. An appropriate lymphadenectomy will be performed. Immediate reconstruction is anticipated if possible.
Intervention MeSH terms: Fluorouracil; Oxaliplatin; Epirubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the esophagus; adenocarcinoma of the stomach; stage III esophageal cancer; stage IV esophageal cancer; stage III gastric cancer; stage IV gastric cancer; stage II esophageal cancer; stage II gastric cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as epirubicin, oxaliplatin, fluorouracil, and
      cisplatin, 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. Giving chemotherapy before surgery may make the tumor smaller and reduce the
      amount of normal tissue that needs to be removed. Giving chemotherapy and radiation therapy
      after surgery may kill any tumor cells that remain after surgery.

      PURPOSE: This phase II trial is studying how well giving combination chemotherapy, surgery,
      and radiation therapy works in treating patients with locoregionally advanced cancer of the
      esophagus, gastroesophageal junction, or stomach.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a histologic diagnosis of adenocarcinoma of the esophagus,
             gastroesophageal junction or gastric cardia, based on biopsy material or adequate
             cytologic exam.

          -  Patients must be clinically staged according to the AJCC 2002 staging system and must
             have either T3-4, or N1 or M1a disease. Staging should include at least an upper
             endoscopy with endoscopic ultrasound and an FDG-PET/CT scan.

          -  Patients must have an ECOG performance status of 0-1.

          -  Patients must have adequate bone marrow function as evidenced by: Absolute neutrophil
             count > 1,500/uL Platelet count > 100,000/uL

          -  Patients must have adequate renal function as evidenced by serum creatinine < 1.6
             mg/dL

          -  Patients must have adequate hepatic function as evidenced by:Serum total bilirubin <
             1.5 mg/dL Alkaline phosphatase < 3X the institutional ULN AST/ALT < 3X the
             institutional ULN

          -  Patients must have adequate pulmonary function as evidenced by an FEV1 > 50%
             predicted.

          -  Patients or their legal representatives must be able to read, understand, provide and
             sign informed consent to participate in the trial.

          -  Patients of childbearing potential agree to use an effective form of contraception
             during the study and for 90 days following the last dose of study medication (an
             effective form of contraception is an oral contraceptive or a double barrier method)

          -  Age > 18 years

        Exclusion Criteria:

          -  Patients with any other diagnosis except for adenocarcinoma (squamous cell carcinoma,
             small cell carcinoma, mixed adenosquamous, lymphoma, sarcoma etc,) will be ineligible.

          -  Patients with any evidence of distant hematogenous or distant nodal disease (M1b) will
             be ineligible.

          -  No prior chemotherapy, radiation therapy or surgery for this malignancy will be
             allowed. Prior endoscopic debulking, laser therapy or dilatation will not exclude a
             patient.

          -  Patients with another active malignancy will not be eligible except for curatively
             treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or
             localized prostate cancer with a current PSA of < 1.0 mg/dL on 2 successive
             evaluations at least 3 months apart, with the most recent evaluation within 4 weeks of
             entry

          -  Patients with an active infection will not be eligible.

          -  Patients with known hypersensitivity to any of the components of oxaliplatin,
             epirubicin, fluorouracil or cisplatin will not be eligible.

          -  Patients who are receiving any other concurrent investigational therapy, or who have
             received investigational therapy within 30 days of the first scheduled day of protocol
             treatment (investigational therapy is defined as treatment for which there is
             currently no regulatory authority approved indication) will not be eligible.

          -  Patients with a baseline peripheral neuropathy greater than or equal Grade 2 will not
             be eligible.

          -  Patients who are pregnant or lactating will not be eligible.

          -  Patients with any other medical condition, including mental illness or substance
             abuse, deemed by the Investigator to be likely to interfere with a patient's ability
             to sign informed consent, cooperate and participate in the study, or interfere with
             the interpretation of the results, will not be eligible.

          -  Patients with any history of an allogeneic transplant will not be eligible.

          -  Patients with known infection with HIV, Hepatitis B or C (active, previously treated
             or both) will not be eligible.