RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Antineoplastons are naturally occurring substances that may
also be made in the laboratory. Antineoplastons may inhibit the growth of cancer cells. It
is not yet known whether giving antineoplastons with chemotherapy is more effective than
chemotherapy alone in treating women with refractory breast cancer.
PURPOSE: This randomized phase II trial is studying methotrexate alone to see how well it
works campared to methotrexate and antineoplaston therapy in treating postmenopausal women
with advanced refractory breast cancer.
- Compare the antitumor activity of antineoplaston A10 with methotrexate vs methotrexate
alone, in terms of objective tumor response, in women with advanced breast cancer.
- Compare the adverse effects of and tolerance to these regimens in these patients.
OUTLINE: This is a randomized study.
- Arm I: Patients receive gradually escalating doses of oral antineoplaston A10 capsules
7 times daily until the maximum tolerated dose is reached, followed by oral
methotrexate capsules 2 to 3 times per day in five days on and five days off courses.
Treatment continues in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive oral methotrexate alone on the same schedule as in arm I.
Tumors are measured every 4 months for 2 years, every 6 months for years 3 and 4, and then
annually for years 5 and 6.
PROJECTED ACCRUAL: A total of 30-70 patients will be accrued for this study within at least
- Histologically confirmed advanced breast cancer that is refractory or unlikely to
respond to hormonal therapy AND failed at least 1 prior chemotherapy regimen
- Symptomatic lymphangitic pulmonary dissemination allowed
- Extensive visceral metastasis allowed
- Patients who are refractory or who have failed to respond after at least 8 weeks of
methotrexate or a methotrexate-containing regimen are not eligible
- Measurable disease
- No bone metastases
- Hormone receptor status:
- Estrogen receptor negative
- Karnofsky 60-100%
- At least 3 months
- WBC at least 3,000/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 2.5 mg/dL
- SGOT no greater than 2 times normal
- Blood ammonia normal
- No hepatic failure
- BUN less than 60 mg/dL
- Creatinine no greater than 2.5 mg/dL
- Creatinine clearance greater than 60 mL/min
- No chronic renal failure
- No severe heart disease
- No severe lung disease
- No serious active infections or fever
- No other concurrent serious disease
- No prior or concurrent secondary malignancies within the past 2 years
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior immunotherapy and recovered
- No concurrent biologic therapy for metastatic breast cancer
- See Disease Characteristics
- At least 4 weeks since prior cytotoxic chemotherapy and recovered
- No other concurrent chemotherapy for metastatic breast cancer
- See Disease Characteristics
- At least 4 weeks since prior hormonal therapy and recovered
- No concurrent hormonal therapy for metastatic breast cancer
- At least 4 weeks since prior radiotherapy and recovered
- No concurrent radiotherapy for metastatic breast cancer
- Not specified
- At least 4 weeks since prior participation in experimental clinical trials
- No prior antineoplaston A10 therapy
- No other concurrent treatment for metastatic breast cancer
- No concurrent salicylates, nonsteroidal anti-inflammatory drugs, phenylbutazone,
phenytoin, and sulfonamides