S0430 Cyclophosphamide and Capecitabine in Treating Women With Stage IV Breast Cancer

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one chemotherapy drug may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cyclophosphamide together with capecitabine works in treating women with stage IV breast cancer.

OBJECTIVES:

* Determine the response rate (complete and partial, confirmed and unconfirmed) in women with stage IV breast cancer treated with oral cyclophosphamide and oral capecitabine.
* Determine the progression-free survival and overall survival of patients treated with this regimen.
* Determine the toxicity of this regimen in these patients.
* Determine the quality of life of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral cyclophosphamide once daily on days 1-14 and oral capecitabine twice daily on days 8-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then at weeks 7, 13, 19, and 25.

After completion of study treatment, patients are followed every 3 months for up to 2 years.

PROJECTED ACCRUAL: A total of 96 patients will be accrued for this study within 4 years.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed stage IV breast cancer

  * Metastatic disease (M1) OR multiple sites of new disease that is clinically obvious metastatic disease (i.e., multiple sites of new osseous disease)
* Meets 1 of the following criteria:

  * Measurable disease
  * Non-measurable disease

    * MUC-1 antigen level \> 2 times upper limit of normal AND level has increased by 1.5 times
* Must have documented MUC-1 antigen level

  * Either cancer antigen (CA) 15-3 or CA 27-29 allowed
* Must have received at least 1 prior hormonal therapy for metastatic disease (estogen receptor-positive patients only)
* No symptomatic brain or CNS metastases

  * Previously treated brain or CNS metastasis allowed provided radiotherapy was completed ≥ 8 weeks before study entry
* Hormone receptor status:

  * Not specified

PATIENT CHARACTERISTICS:

Age

* 18 and over

Sex

* Female

Menopausal status

* Not specified

Performance status

* Zubrod 0-2

Life expectancy

* Not specified

Hematopoietic

* No known existing uncontrolled coagulopathy

Hepatic

* Not specified

Renal

* Creatinine clearance \> 40 mL/min

Cardiovascular

* No congestive heart failure
* No symptomatic coronary artery disease
* No cardiac arrhythmia not well controlled with medication
* No myocardial infarction within the past 12 months
* No other clinically significant cardiac disease

Gastrointestinal

* Able to take oral medication
* No uncontrolled nausea, vomiting, or diarrhea
* No lack of physical integrity of the upper gastrointestinal tract
* No malabsorption syndrome

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No active infection requiring systemic therapy
* No prior severe reaction to fluoropyrimidines
* No known sensitivity to fluorouracil
* No known dihydropyrimidine dehydrogenase deficiency
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent immunotherapy or biologic therapy for breast cancer
* No concurrent gene therapy for breast cancer
* No concurrent filgrastim (G-CSF)

Chemotherapy

* At least 14 days since prior chemotherapy and recovered
* No more than 2 prior chemotherapy regimens for metastatic disease
* No prior capecitabine for metastatic disease
* No prior oral cyclophosphamide for metastatic disease

  * Prior IV cyclophosphamide allowed
* No other concurrent chemotherapy for breast cancer

Endocrine therapy

* See Disease Characteristics
* No concurrent hormonal therapy for breast cancer

Radiotherapy

* See Disease Characteristics
* At least 14 days since prior radiotherapy to non-CNS disease sites and recovered
* No concurrent radiotherapy for breast cancer

Surgery

* Not specified

Other

* Concurrent bisphosphonates allowed
* No concurrent full-dose warfarin

  * Concurrent prophylactic warfarin (≤ 1 mg/day) to maintain port patency allowed
* No other concurrent antineoplastic therapy for breast cancer