A Phase I/II Study of Capecitabine (XELODA®, Roche) Plus Oxaliplatin (Eloxatin®, Sanofi) Plus ZD 1893 (IRESSA®) in the Treatment of Metastatic Colorectal Cancer

Date de début de l'étude : 1 janvier 2004

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed\* colorectal cancer * Metastatic disease * The site of the primary tumor must have been confirmed endoscopically, radiologically, or surgically to be the colon or rectum NOTE: \*Confirmation is not required for recurrent metastatic disease unless an interval of \> 5 years has elapsed between the initial primary surgery and the development of metastases * Measurable disease * At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan * No CNS metastases PATIENT CHARACTERISTICS: Age * 18 to 80 Performance status * ECOG 0-1 Life expectancy * More than 3 months Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9 g/dL (transfusion allowed) Hepatic * AST and ALT ≤ 3 times upper limit of normal (ULN) * Bilirubin ≤ ULN * No unstable or uncompensated hepatic disease Renal * Creatinine \< 1.5 times ULN OR * Creatinine clearance \> 60 mL/min * No unstable or uncompensated renal disease Cardiovascular * No unstable or uncompensated cardiac disease Pulmonary * No evidence of clinically active interstitial lung disease * Asymptomatic patients with chronic stable radiographic changes are eligible * No unstable or uncompensated respiratory disease Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after study participation * No known hypersensitivity to gefitinib or any of its excipients * No known hypersensitivity to platinum compounds, fluorouracil, or capecitabine * No severe or uncontrolled systemic disease * Able to receive oral medication * No known dihydropyrimidine dehydrogenase (DPD) deficiency * No known peripheral neuropathy ≥ grade 1 * Absence of deep tendon reflexes as the sole neurological abnormality allowed * No other significant clinical disorder or laboratory finding that would preclude study participation * No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix (phase II only) PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * At least 4 weeks since prior chemotherapy for metastatic colorectal cancer (phase I) * No prior chemotherapy for metastatic disease (phase II) * Prior fluorouracil and leucovorin calcium in the adjuvant setting allowed provided the last treatment was administered more than 6 months before the development of metastatic disease * No prior irinotecan and oxaliplatin (phase II) Endocrine therapy * Not specified Radiotherapy * No concurrent radiotherapy for colorectal cancer Surgery * See Disease Characteristics * More than 4 weeks since prior major surgery (e.g., laparotomy) Other * Recovered from all prior therapy (no unresolved chronic toxicity \> grade 2) * More than 4 weeks since prior investigational drugs * No prior epidermal growth factor receptor inhibitor therapy (phase II) * No concurrent phenytoin, carbamazepine, rifampin, barbiturates, or Hypericum perforatum (St. John's wort) * No other concurrent investigational drugs * No other concurrent systemic therapy for colorectal cancer