Irinotecan and Capecitabine in Treating Women With Advanced Breast Cancer

OBJECTIVES:

• Determine the maximum tolerated dose of capecitabine and irinotecan in women with advanced breast cancer.
• Determine the degree of accumulation of cells in S-phase in tumor biopsies from patients treated with this regimen.
• Determine the dose-limiting toxicity and other major or unusual toxic effects of this regimen in these patients.
• Determine any antitumor activity of this regimen in these patients.
• Determine the pharmacokinetics of this regimen, including the active metabolite SN-38, in these patients.
• Correlate pharmacokinetic parameters of this regimen with the biological changes observed in these patients.
• Determine, preliminarily, the relationship of tumor response with modulation of S-phase in patients treated with this regimen.

OUTLINE: This is a dose-escalation study.

Patients receive irinotecan IV over 1.5 hours on days 1, 8, 22, and 29 and oral capecitabine twice daily on days 1-14 and 23-36. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 8-37 patients will be accrued for this study within 18-24 months.

DISEASE CHARACTERISTICS:

• Diagnosis of breast cancer not eligible for potentially curative therapy or studies of higher priority

• Advanced disease
• Tumor accessible to biopsy AND not irradiated
• Failed at least 1 prior chemotherapy regimen (not including adjuvant chemotherapy)
• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL

Hepatic

• AST ≤ 2 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 50 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No active uncontrolled bacterial, viral, or fungal infection
• No poor medical risk from non-malignant systemic disease

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• Prior irinotecan allowed
• Prior carboplatin allowed
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy except for small port radiotherapy for local control

Surgery

• More than 4 weeks since prior major surgery

Other

• No concurrent high-dose IV cyclosporine