Chemotherapy and Radiation Therapy After Surgery in Treating Patients With Stomach or Esophageal Cancer
Condition: Esophageal Cancer; Gastric Cancer
MeSH terms: Stomach Neoplasms; Esophageal Neoplasms
Intervention: cisplatin; epirubicin hydrochloride; fluorouracil; leucovorin calcium; radiation therapy
Intervention description: Given IV; Given IV; Given IV; Given IV; Given 5 days a week for 5 weeks
Intervention MeSH terms: Leucovorin; Fluorouracil; Epirubicin; Calcium; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 546.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage I gastric cancer; stage II gastric cancer; stage III gastric cancer; adenocarcinoma of the stomach; adenocarcinoma of the esophagus; stage I esophageal cancer; stage II esophageal cancer; stage III esophageal cancer

Summary:

      RATIONALE: Drugs used in chemotherapy 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 after surgery may kill any remaining tumor
      cells following surgery. It is not yet known which chemotherapy and radiation therapy regimen
      is more effective in treating stomach or esophageal cancer.

      PURPOSE: Randomized phase III trial to compare two different chemotherapy and radiation
      therapy regimens in treating patients who have undergone surgery for stomach or esophageal
      cancer.
    

Eligibility criteria:

        1. Required Tumor Parameters

             1.1 Patients must have histologically diagnosed adenocarcinoma of the stomach or
             gastroesophageal junction. Adenocarcinomas of the esophagus that are not involving the
             gastroesophageal junction are not eligible.

             1.2 Patients must have had en bloc resection of all known tumor. The surgical
             resection must have been done with a curative intent.

             1.3 Patients must have tumor extension beyond muscularis propria and/or nodal
             involvement without evidence of M1 disease.

               -  Patients can have stages IB if there is evidence of either node-positive (N1)
                  disease or tumor extension beyond the muscularis propria (i.e., T1, N1, M0
                  patients are eligible but patients with T2, N0, M0 are allowed only if there is
                  extension beyond the muscularis propria).

               -  Patients can have stages II, IIIA, IIIB or stage IV with M0 (i.e., T4N2M0).

               -  Stages 0, IA, or any stage with M1 are not allowed. (see Appendix I for TNM
                  staging guide).

             1.4 Patients with known unresected cancer, recurrent cancer, microscopic evidence of
             tumor at the distal or proximal line of stomach resection, noncontiguous resection of
             tumor, or M1 (metastatic) disease are ineligible.

          2. Prior Therapy

             2.1 No prior therapy (except hormonal or biologic) for other malignancies is allowed
             except for adequately treated basal cell or squamous cell skin cancer, noninvasive
             carcinoma in situ which has been fully resected, or other cancer for which the patient
             has been disease free for five years.

             2.2 Patients who have had any previous chemotherapy or radiotherapy are ineligible.

          3. Patient Characteristics

             3.1 Patients must have an ECOG (CTC) performance status of 0, 1 or 2.

             3.2 Patients are required to have an adequate total caloric intake to allow them to
             maintain their post-surgical body weight. Patients must have documentation of stable
             weight (or less than 2 pounds weight loss) for at least one week prior to
             registration.

             3.3 All patients must be evaluated by a radiation oncologist (prior to enrollment) to
             ensure that the patient is an appropriate candidate for radiation therapy.

             3.4 Patients may not have unilateral renal function (only one functioning kidney) as
             determined by CT scan with contrast, urogram, renal scan, or other study.

             3.5 Pregnant or lactating women may not participate. Men and women of reproductive
             potential may not participate unless they have agreed to use an effective
             contraceptive method or practice abstinence while in this study.

               -  The effects of therapeutic radiotherapy are known to be teratogenic.

               -  The effects of Epirubicin, Cisplatin, and 5-FU on a developing human fetus at the
                  recommended therapeutic dose are less well known.

               -  For this reason and because DNA alkylating agents are known to be teratogenic,
                  women of childbearing potential and men must agree to use adequate contraception
                  (hormonal or barrier method of birth control) prior to study entry and for the
                  duration of study participation.

               -  Should a woman become pregnant or suspect she is pregnant while participating on
                  this study, she should inform her treating physician immediately. Because the
                  risk of toxicity in nursing infants secondary to Epirubicin, Cisplatin, and 5-FU
                  treatment of the mother is unknown but may be harmful, breastfeeding should be
                  discontinued.

             3.6 Patients with any of the following cardiac conditions are ineligible:

               -  Uncontrolled high blood pressure

               -  Unstable angina

               -  Symptomatic congestive heart failure

               -  Myocardial infarction < 6 months prior to registration

               -  Serious uncontrolled cardiac arrhythmia

               -  New York Heart Association classification III or IV.

             3.7 No uncontrolled serious medical or psychiatric illness which would prevent
             compliance with treatment or adequate informed consent.

             3.8 Patients with active infectious process are ineligible.

             3.9 Patients with grade 2 or greater peripheral neuropathy at baseline are ineligible.

          4. Required Initial Laboratory Values:

               -  Granulocytes ≥ 1,500/μl

               -  Platelet count ≥ 100,000/μl

               -  Creatinine ≤ 1.5 mg/dl

               -  Bilirubin ≤ 2.0 mg/dl

               -  AST ≤ 3x upper limits of normal