Irinotecan in Treating Patients With Refractory Metastatic Breast Cancer

OBJECTIVES: I. Assess the antitumor activity and toxicity of two different schedules of
irinotecan in the treatment of patients with refractory metastatic breast cancer who have
received 1 or 2 previous chemotherapy regimens (up to one prior therapy for metastatic
disease and one for adjuvant therapy). II. Compare the time to progression, survival, and
quality of life of these patients on these 2 different schedules of irinotecan.

OUTLINE: This is a randomized study. Patients are stratified according to dominant disease
(visceral vs nonvisceral), performance status (0-1 vs 2), and prior chemotherapy in
metastatic setting (yes vs no). Patients assigned to arm I receive irinotecan intravenously
over 90 minutes every week for 4 weeks followed by a 2 week rest period. Treatment is
repeated every 6 weeks in the absence of disease progression or unacceptable toxicity.
Patients assigned to arm II receive irinotecan intravenously over 90 minutes every 3 weeks
for 6 weeks. Treatment is repeated every 6 weeks in the absence of disease progression or
unacceptable toxicity. Quality of life is assessed before and during treatment. Patients are
followed every 3 months for 2 years, then annually for 1 year.

PROJECTED ACCRUAL: A total of 42-100 patients (21-50 patients per arm) will be accrued for
this study within 3.5 years.

DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the breast with
progressing locoregional or metastatic disease Measurable or evaluable indicator lesion No
uncontrolled CNS metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy:
Greater than 3 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet
count at least 100,000/mm3 Hepatic: Bilirubin no greater than 0.3 mg/dL above upper limit
of normal (ULN) AST no greater than 3 times ULN Renal: Creatinine no greater than 1.0
mg/dL above ULN Cardiovascular: No New York Heart Association class III or IV heart
disease Other: No uncontrolled infection No chronic debilitating disease Not pregnant or
lactating Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks
since chemotherapy No more than 2 prior chemotherapy regimens for metastatic disease No
more than 1 prior chemotherapy regimen in the adjuvant setting At least 1 prior regimen
containing taxane or doxorubicin for metastatic disease or in the adjuvant setting
Endocrine therapy: Not specified Radiotherapy: No radiotherapy to greater than 25% of bone
marrow No prior treatment with strontium 89 Surgery: At least 4 weeks since major surgery
Other: No concurrent metoclopramide