Cisplatin and Irinotecan Chemotherapy, Followed by ZD 1839 (Iressa) in Patients With Esophageal or Gastric Carcinomas

Inclusion Criteria: * Histologic confirmation of esophageal carcinoma (squamous or adenocarcinoma) or gastric adenocarcinoma. * Surgically unresectable disease and/or metastatic disease. * No prior chemotherapy therapy. * Life expectancy \> 12 weeks. * Patients must have the ability to take and retain oral medications. * Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Karnofsky Performance Status \[KPS\] ≥50%). * Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria and computerized tomographic scan performed within 28 days prior to registration. * Organ system function assessed within 7 days prior to registration and within the following parameters: * Absolute neutrophil count ≥1500/mL; * Platelet count ≥100,000/mL; * Hemoglobin level ≥10.0 gm/dL; * Serum creatinine ≤1.5 x IULN (Institutional Upper Limits of Normal); OR Measured creatinine clearance ≥60 mL/min; * AST (SGOT) or ALT (SGPT) ≤ 2.5 x IULN (unless the liver is involved by tumor, in which case it must be ≤5.0 x IULN); * Total bilirubin ≤1.5 x IULN. * Understanding of the subject of the potential and unknown teratogenic risk, as well as their willingness to practice birth control. Should a pregnancy occur while a subject, either father or mother, is receiving study medication, the subject should inform the doctor immediately. * Aged 18 years or older * Provision of written informed consent * For patients with locally advanced disease, subjects must be evaluated by a radiation oncologist prior to study entry, and judged that radiation therapy is not indicated in the subjects therapy. Exclusion Criteria: * Prior treatment with EGFR-inhibiting agents, chemotherapy, or radiotherapy for esophagogastric carcinomas. * Patients must not be receiving any other investigational agents. Use of erythropoietin is allowable. Secondary prophylaxis with granulocyte colony stimulating factor (G-CSF) (Filgrastim) is allowable. The use of granulocyte-macrophage colony stimulating factor (GM-CSF) (Sargramostim) is not allowed on this protocol. * Uncontrolled brain metastases. * Patients must not have uncontrolled intercurrent illness at the time of registration including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina, pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients must not have current New York Heart Association Class III or IV heart disease. * Known human immunodeficiency virus (HIV) infection. * Pregnant or breast-feeding women. * Patients who have had prior malignancies, except non-melanoma skin cancer (basal or squamous cell carcinoma) are not eligible for this study; unless greater than 5 years has passed since the event. * Known severe hypersensitivity to ZD 1839 or any of the excipients of this product. * Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St. John's Wort. * Treatment with a non-approved or investigational drug within 30 days before Day 1 of trial treatment. * Incomplete healing from previous oncologic or other major surgery. * Serum creatinine level greater than Common Toxicity Criteria (CTC) grade 2. * Any evidence of clinically active interstitial lung disease. Subjects with chronic stable radiographic changes who are asymptomatic need not be excluded.