LY231514 Plus Gemcitabine in Treating Women With Metastatic Breast Cancer

OBJECTIVES:

- Assess the antitumor activity of pemetrexed disodium in combination with gemcitabine in
the treatment of women with metastatic breast cancer who have received an anthracycline
and a taxane in the adjuvant and/or metastatic setting and no more than 1 chemotherapy
regimen for metastatic disease (unless these were a taxane and anthracycline).

- Determine the toxicity of this regimen in this patient population.

- Determine time to progression and overall survival of these patients receiving this
regimen.

OUTLINE: Patients receive gemcitabine IV over 30 minutes on days 1 and 8. pemetrexed
disodium IV is administered over 10 minutes 90 minutes following gemcitabine on day 8.
Treatment continues every 21 days for a minimum of 6 courses in the absence of unacceptable
toxicity or disease progression. Patients achieving a complete response receive 2 additional
courses.

Patients are followed every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed breast cancer with clinical evidence of
metastatic disease

- Bidimensionally measurable disease

- If bisphosphonates used, must have measurable disease site other than bone

- No bone only disease

- Must have received a prior anthracycline and taxane in the adjuvant and/or metastatic
setting

- No clinically significant pericardial effusions, pleural effusions, or ascites unless
they can be drained

- No active CNS metastases

- Treated CNS metastasis that has ben stable for at least 8 weeks allowed

- 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 at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

Hepatic:

- Bilirubin no greater than 2 times upper limit of normal (ULN)

- AST no greater than 3 times ULN (5 times ULN if liver metastases)

- Albumin at least 3.0 g/dL

Renal:

- Creatinine clearance at least 45 mL/min

Cardiovascular:

- No New York Heart Association class III or IV heart disease

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to take folic acid and cyanocobalamin (vitamin B12) supplements

- Body surface area less than 3 m^2

- No uncontrolled infection

- No chronic debilitating disease

- No other prior malignancy within the past 5 years except adequately treated basal
cell or squamous cell skin cancer or adequately treated noninvasive carcinomas

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 4 weeks since prior immunotherapy

- At least 4 weeks since prior genetic therapy

- No concurrent immunomodulating agents

Chemotherapy:

- See Disease Characteristics

- No more than 3 prior chemotherapy regimens including adjuvant therapy

- No more than 1 prior chemotherapy regimen for metastatic disease unless these
were a taxane and anthracycline

- At least 4 weeks since prior chemotherapy

- No prior gemcitabine and/or pemetrexed disodium

- No other concurrent cytostatic or cytotoxic chemotherapy

Endocrine therapy:

- Not specified

Radiotherapy:

- At least 4 weeks since prior radiotherapy

- No prior radiotherapy to greater than 25% of bone marrow

- No prior strontium chloride Sr 89

- No concurrent radiotherapy

Surgery:

- At least 4 weeks since prior major surgery

Other:

- No aspirin or nonsteroidal antiinflammatory agents 2 days before, the day of, and for
2 days after pemetrexed disodium administration (5 days before for long acting agents
such as naproxen, piroxicam, diflunisal, or nabumetone)