Clinical Drug Experience Knowledgebase

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed metastatic breast cancer
Received at least 2 prior courses of paclitaxel-based chemotherapy at doses between 175-200 mg/m^2 (given over 3 hours every 3 weeks) or docetaxel-based chemotherapy at doses between 75-100 mg/m^2 (given over 1 hour every 3 weeks) as most recent anticancer therapy

Evidence of disease resistance

Progressive disease as best response OR
Transient response or disease stabilization followed by progression during taxane-based treatment
Disease progression on a combination of a taxane and another cytotoxic agent allowed

Unidimensionally measurable disease

At least 1 target lesion that clearly progressed or developed during prior taxane therapy
Lesions stable or responsive to prior taxane therapy are not considered target lesions
Lesions that have been irradiated within the past 3 months are not considered target lesions unless they have clearly progressed or appeared since radiotherapy
No bone metastases as only site of measurable disease
No rapidly progressive visceral metastases
No symptomatic CNS metastases

Hormone receptor status:

Not specified

PATIENT CHARACTERISTICS:

Age:

18 and over

Sex:

Not specified

Menopausal status:

Not specified

Performance status:

WHO 0-2

Life expectancy:

Not specified

Hematopoietic:

Neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic:

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
Transaminases no greater than 2.5 times ULN (5 times ULN if liver metastases present)

Renal:

Creatinine no greater than 1.5 times ULN
Calcium normal

Cardiovascular:

LVEF normal by echocardiogram (ECG) or MUGA scan
QTc less than 450 sec on baseline ECG
No prior clinically significant arrhythmias requiring treatment
No cardiac infarction
No atrial ventricular enlargement or hypertrophy

Other:

No prior toxicity to paclitaxel that would preclude study dose and schedule
Sodium, potassium, chloride, and bicarbonate normal
No pre-existing neuropathy greater than grade 2
No other prior or concurrent malignancy except adequately treated carcinoma in situ of the cervix, contralateral breast cancer, or nonmelanoma skin cancer or cancer that has been in remission for more than 5 years
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No concurrent anticancer biologic agents

Chemotherapy:

See Disease Characteristics
No more than 8 weeks since last course of prior taxane-based chemotherapy
No more than 2 prior chemotherapy regimens for metastatic breast cancer
No other concurrent anticancer chemotherapy

Endocrine therapy:

No concurrent anticancer hormonal therapy

Radiotherapy:

See Disease Characteristics
No concurrent radiotherapy

Surgery:

Not specified

Other:

No prior multi-drug resistance inhibitor
No new anticancer therapy initiation since last course of prior taxane-based chemotherapy
No concurrent angiotensin converting enzyme inhibitor and/or drugs that may prolong the QTc interval
No other concurrent anticancer therapy
Concurrent bisphosphonates for treatment and prevention of bony metastases allowed provided drugs were initiated prior to study (treatment of hypercalcemia due to malignancy allowed regardless of time of initiation)