Irinotecan and Docetaxel in Treating Patients With Refractory Metastatic Breast Cancer

OBJECTIVES:

Primary

- Determine the antitumor activity of irinotecan and docetaxel, in terms of response
rate, in patients with refractory metastatic breast cancer.

Secondary

- Determine the toxicity profile of this regimen in these patients.

- Determine the progression-free and overall survival of patients treated with this
regimen.

OUTLINE: This is a multicenter study.

Patients receive docetaxel IV over 1 hour followed by irinotecan IV over 1 hour on days 1
and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable
toxicity. Patients who achieve a complete response (CR) receive 2 additional courses beyond
CR.

Patients are followed every 2 months until disease progression and then every 6 months
thereafter.

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the breast

- Metastatic disease

- Previously treated with chemotherapy in the adjuvant setting and/or for metastatic
disease

- At least one unidimensionally measurable lesion

- At least 20 mm by CT scan or MRI OR at least 10 mm by spiral CT scan

- Superficial clinical lesions (e.g., skin nodules or palpable lymph nodes) are
allowed

- Lesions on chest x-ray are allowed provided they are clearly defined and
surrounded by aerated lung

- The following are not considered measurable:

- Bone lesions

- Ascites

- Leptomeningeal disease

- Pleural/pericardial effusion

- Inflammatory breast disease

- Lymphangitis cutis/pulmonis

- Cystic lesions

- No known CNS metastases unless controlled by prior surgery and/or radiotherapy

- Hormone receptor status:

- Estrogen receptor (ER) and/or progesterone receptor (PR) status known

PATIENT CHARACTERISTICS:

Age

- 18 and over

Sex

- Male or female

Menopausal status

- Not specified

Performance status

- ECOG 0-2

Life expectancy

- At least 3 months

Hematopoietic

- Granulocyte count ≥ 1,500/mm^3

- Hemoglobin ≥ 8.0 g/dL

- Platelet count ≥ 100,000/mm^3

Hepatic

- Bilirubin ≤ upper limit of normal (ULN)

- Meets 1 of the following criteria:

- AST or ALT ≤ ULN AND alkaline phosphatase ≤ 5 times ULN

- Alkaline phosphatase ≤ ULN AND AST or ALT ≤ 5 times ULN

- AST or ALT ≤ 1.5 times ULN AND alkaline phosphatase ≤ 2.5 times ULN

Renal

- Creatinine ≤ 1.5 times ULN

Cardiovascular

- No myocardial infarction within the past 180 days

- No congestive heart failure

- No unstable angina

- No clinically significant pericardial effusion or arrhythmias

Other

- No active, unresolved infection

- No prior severe hypersensitivity reaction to docetaxel, irinotecan, or any drug
formulated with polysorbate 80

- No other malignancy within the past 5 years except curatively treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix

- No grade 1 or greater sensory or motor neuropathy

- No other concurrent severe condition that would preclude study participation

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Prior trastuzumab (Herceptin®) required for HER-2-positive patients (unless
contraindicated)

Chemotherapy

- See Disease Characteristics

- More than 14 days since prior chemotherapy

- No more than 2 prior chemotherapy regimens for metastatic disease

- No prior irinotecan or docetaxel for metastatic disease

- Docetaxel as adjuvant therapy allowed

- No other concurrent chemotherapy

Endocrine therapy

- Prior hormonal therapy required for patients with ER- and/or PR-positive tumors
(unless contraindicated)

Radiotherapy

- See Disease Characteristics

- At least 30 days since prior radiotherapy

- No concurrent radiotherapy

Surgery

- See Disease Characteristics

- At least 3 weeks since prior major surgery and recovered

Other

- More than 7 days since prior parenteral antibiotic therapy

- No other concurrent experimental drugs