LY231514 Plus Gemcitabine in Treating Women With Metastatic Breast Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining LY231514 plus gemcitabine in treating women who have 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.

Eligibility Criteria:
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)