Interleukin-2 With or Without Histamine Dihydrochloride in Treating Patients With Metastatic Kidney Cancer

A Randomized Phase II Study to Evaluate the Efficacy of Combined Immunotherapy With Subcutaneous Interleukin-2 and Maxamine in Patients With Metastatic Renal Cell Carcinoma

RATIONALE: Interleukin-2 may stimulate a person's white blood cells to kill kidney cancer cells. Histamine dihydrochloride may prolong survival and improve quality of life in patients with metastatic kidney cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of interleukin-2 with or without histamine dihydrochloride in treating patients who have metastatic kidney cancer.

OBJECTIVES:

• Determine the clinical efficacy and safety of subcutaneous (SC) histamine dihydrochloride given in conjunction with SC recombinant human interleukin-2 in patients with stage IV renal cell carcinoma in terms of survival at 1 year, objective tumor response rate, duration of response, and median survival.

OUTLINE: This is a randomized, open label study. Patients are randomized to receive interleukin-2 (IL-2) with or without histamine dihydrochloride.

• Arm I: Patients receive IL-2 subcutaneously (SC) once daily and histamine dihydrochloride SC twice daily on days 1-5 of weeks 1-3 followed by 2 weeks of rest.
• Arm II: Patients receive IL-2 as in arm I. Treatment continues for a minimum of 2 courses in both arms in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 60 patients (30 per arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic renal cell carcinoma
• Bidimensionally measurable disease
• No clinical evidence of CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 to 75

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• Hemoglobin greater than 10.0 g/dL
• WBC greater than 3,000/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• PTT normal
• Bilirubin less than 1.25 times upper limit of normal (ULN)

Renal:

• Creatinine less than 1.5 times ULN

Cardiovascular:

• No abnormal cardiac function by resting ECG

Pulmonary:

• FEV and FVC at least 70% predicted
• SaO2 at least 90% by pulse oximetry

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No clinically significant acute viral, bacterial, or fungal infection requiring specific therapy
• No pheochromocytoma
• No glaucoma
• No other concurrent ongoing active malignancy except carcinoma in situ of the cervix or localized squamous or basal cell carcinoma of the skin
• No serious recent nonmalignant medical complication that would preclude study therapy
• No organ grafts except skin grafts, blood transfusions, or bone marrow or stem cell transplantation
• No prior documented asthma or systemic allergic reaction within past 5 years
• No history of seizures, CNS disorders, or psychiatric disability that would preclude study compliance
• No medical, sociologic, or psychological impediment that would preclude study compliance
• No active peptic or esophageal ulcer disease
• No prior peptic or esophageal ulcer disease with history of bleeding
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
• No concurrent chemotherapy

Endocrine therapy:

• At least 24 hours since prior steroids
• No concurrent steroids including steroid therapy for documented adrenal failure or septic shock
• Concurrent noncorticosteroid hormones for nonmalignancy conditions allowed

Radiotherapy:

• At least 4 weeks since prior extensive radiotherapy
• No concurrent radiotherapy to measurable malignant masses

Surgery:

• Not specified

Other:

• At least 24 hours since prior beta blockers or clonidine
• No other concurrent systemic antimalignancy therapy
• No other concurrent antitumor agents
• No other concurrent investigational agents
• No concurrent beta blockers or clonidine
• No concurrent H2 receptor antagonists (e.g., Zantac, Tagamet) (arm I only)
• No concurrent antihistamines except to treat acute colds or allergy symptoms