• Tumor response [ Designated as safety issue: No ]
  
• Toxcity [ Designated as safety issue: No ]
  

OBJECTIVES:

• Evaluate tumor response and toxicity induced by fluorouracil and doxorubicin HCl liposome combined with mild systemic hyperthermia in patients with metastatic breast, ovarian, endometrial, or cervical cancer.

OUTLINE: This is a time-escalation study of systemic hyperthermia.

Patients receive fluorouracil IV continuously over 24 hours on days 1-5 and doxorubicin HCl liposome IV over 30 minutes on day 6. Beginning on day 7, patients receive heat applied for 6-24 hours (in 6-hour sequential treatments) using a mild hyperthermia-induction device. Treatment repeats every 4-5 weeks for a total of 4 courses. Patients who achieve less than a complete response but have no disease progression may receive additional courses of chemotherapy alone.

Cohorts of 5 patients receive escalating durations of hyperthermia until the recommended phase II duration is determined. The recommended phase II duration of hyperthermia is defined as the level preceding that at which 1 of 5 patients experiences measurable toxicity. (Phase I closed as of 9/28/01)

Patients are followed at 4 weeks and then every 6 months for 1 year.

PROJECTED ACCRUAL: A maximum of 34 patients will be accrued for this study within 48 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic breast, ovarian, endometrial, or cervical carcinoma
• Measurable and evaluable disease
• No brain metastases
• No hepatic involvement greater than 80%
• No lung involvement greater than 30%

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Not specified

Menopausal status:

• Not specified

Performance status:

• Zubrod 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute granulocyte count greater than 1,500/mm^3
• Platelet count greater than 90,000/mm^3
• Normal bone marrow cellularity on bone marrow biopsy
• Thrombin time less than 17 sec
• Fibrinogen greater than 200 mg/dL
• FSP less than 40
• No coagulopathy

Hepatic:

• Bilirubin less than 2.0 mg/dL
• SGPT less than 2 times normal
• PT less than 14 sec
• PTT less than 35 sec

Renal:

• BUN less than 25 mg/dL
• Creatinine clearance at least 45 mL/min

Cardiovascular:

• Normal cardiovascular system
• Resting ventricular ejection fraction greater than 40%
• No prior myocardial infarction
• No symptomatic coronary artery disease
• No unstable blood pressure
• No thromboembolic disease

Neurologic:

• No seizures or other CNS disorders
• Negative computerized tomographic scan of brain

Pulmonary:

• FEV_1 greater than 70% of predicted
• Arterial pressure of oxygen greater than 60 mmHg on room air with appropriate pressure of carbon dioxide and pH values
• No history of cardiopulmonary or respiratory disease

Other:

• No other serious concurrent medical illness
• No diabetes mellitus

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Prior chemotherapy allowed

Endocrine therapy:

• No adrenal corticosteroids

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No concurrent cardiac glycosides, antianginal therapy, or antiarrhythmics
• No concurrent vasodilators, anticoagulants, thrombolytic agents, or aspirin