OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxic effects of interleukin-12 and interleukin-2 in patients with refractory or advanced solid tumors.
• Assess the pharmacokinetics of this treatment regimen in these patients.
• Assess the antitumor effect of this treatment regimen in this patient population.
• Determine the immunomodulatory activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

• Part I: Patients receive interleukin-2 IV over 15 minutes every 8 hours on days 1 and 9 and interleukin-12 IV on days 2, 4, 6, 10, 12, and 14. Treatment continues every 35 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of interleukin-12 and interleukin-2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Part II: Once the MTD is determined, an additional 10 patients are treated at the MTD.

Patients are followed at 3 weeks.

PROJECTED ACCRUAL: A total of 24-34 patients will be accrued for part I and total of 10 patients will be accrued part II of the study within approximately 2 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed refractory or advanced nonhematologic malignancy (e.g., breast, lung, or renal cell cancer or sarcoma) for which no curative therapy exists

  • Patients with renal cell cancer must have specifically refused or been ineligible to receive prior interleukin-2
• Evaluable disease
• No clinically significant pleural effusion
• No prior or concurrent brain metastases

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Not specified

Menopausal status:

• Not specified

Performance status:

• ECOG 0-1

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3
• No history of congenital or acquired coagulation disorder

Hepatic:

• Bilirubin less than 2.0 mg/dL
• Transaminases less than 2.5 times upper limit of normal
• Hepatitis B negative

Renal:

• Creatinine less than 2.0 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No history of coronary artery disease, angina, or myocardial infarction
• Normal stress thallium testing if over the age of 50

Pulmonary:

• Normal pulmonary function, defined as DLCO more than 60% predicted and FEV1 more than 70% predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 2 months after study
• HIV negative
• No concurrent acute infection
• No other systemic illness (not critically ill or medically unstable)
• No malignant hyperthermia
• No prior or concurrent autoimmune disease
• No history of ongoing or intermittent bowel obstruction

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• At least 4 weeks since prior immunotherapy, filgrastim (G-CSF) or sargramostim (GM-CSF), interferons or interleukins, epoetin alfa, or intravenous immunoglobulins
• No prior therapy with IL-2
• No prior interleukin-12
• No prior bone marrow or stem cell transplantation
• No other concurrent cytokines or potential immunomodulators

Chemotherapy:

• At least 4 weeks since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• At least 4 weeks since prior systemic corticosteroids, growth hormone treatment, or myelosuppressive hormonal therapy
• No concurrent hormonal therapy (including oral contraceptives) except systemic corticosteroids in the case of life-threatening complications such as Pneumocystis carinii pneumonia

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• Concurrent radiotherapy allowed if it is not necessitated by disease progression

Surgery:

• Not specified

Other:

• At least 4 weeks since prior investigational agents
• At least 4 weeks since prior tretinoin
• No other concurrent investigational agents
• No concurrent tretinoin