RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of irinotecan and capecitabine in treating
patients who have solid tumors that have not responded to previous treatment.
OBJECTIVES: I. Determine the maximum tolerated dose and toxic effects of irinotecan and oral
capecitabine in patients with gastrointestinal or other solid tumors. II. Characterize the
relationship at the recommended phase II dose between thymidine synthase and thymidine
phosphorylase expression and tumor response and/or toxic effects in these patients.
OUTLINE: This is a dose escalation study. Patients receive oral capecitabine twice daily
every twelve hours for 14 days, and IV irinotecan over 30 minutes once every 3 weeks
beginning on day 1. Treatment continues for at least 2 courses in the absence of disease
progression or unacceptable toxicity. The dose of capecitabine and irinotecan is escalated
in cohorts of 3-6 patients until the maximum tolerated dose (MTD) is determined. The MTD is
defined as the dose at which 2 of 6 patients experience dose limiting toxicity.
PROJECTED ACCRUAL: Approximately 25-30 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Histologically confirmed solid tumors, including but not limited
to breast, gastrointestinal, and unknown primary cancer that is refractory to standard
therapy or for which no standard therapy exists No known bone marrow involvement
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life
expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 OR
WBC at least 3,500/mm3 AND Platelet count at least 100,000/mm3 Hepatic: Bilirubin no
greater than 1.5 mg/dL No known Gilbert's syndrome No other significant hepatic disease
requiring medication Renal: Creatinine no greater than 1.5 mg/dL Cardiovascular: No
significant cardiac disease requiring medication Other: Not pregnant or nursing Fertile
patients must use effective contraception No other significant medical condition
PRIOR CONCURRENT THERAPY: Biologic therapy: At least 2 weeks since prior colony
stimulating factor and other cytokines active on bone marrow Chemotherapy: At least 4
weeks since prior chemotherapy (6 weeks since mitomycin or nitrosoureas) No prior or
concurrent irinotecan and fluorouracil therapy Endocrine therapy: Not specified
Radiotherapy: At least 4 weeks since prior radiotherapy No concurrent radiotherapy
Surgery: Recovered from prior major surgery