Aldesleukin

Mechanism of Action
Inhibits tumor growth; exerts immunologic effects by activating the cellular immunity to increase lymphocytes, eosinophils, platelets, and cytokines, including tumor necrosis factor, interleukin-1, and gamma interferon.

Indications
Metastatic renal cell carcinoma in adults.
Metabolism/Excretion
Metabolized in the kidney; excreted in the urine. Serum half-life: 13 minutes after IV administration. Eliminated in 85 minutes.

Dosage Range
¨ Adult: 600,000 IU/kg (0.037 mg/kg) given every 8 hours by a 15-minute IV infusion for a total of 14 doses. After 9 days of rest, repeat the schedule for another 14 doses, for a maximum of 28 doses per cycle. Doses may be held for toxicities. Retreatment may be given if response to treatment is noted after 4 weeks. The patient should have a rest period of at least 7 weeks from the date of discharge before retreatment.

¨ Pediatric: Safety and efficacy not established.
Drug Preparation/Stability
Supplied in powder for injection: single-use, preservative-free vials contain 22 million IU (1.3 mg) of aldesleukin. Reconstitute with 1.2 mL sterile water for injection. When reconstituted, each milliliter contains 18 million IU (1.1 mg) of aldesleukin. Do not reconstitute with bacteriostatic water or sodium chloride. Store powder and reconstituted solution in the refrigerator at 2° to 8°C (36° to 46°F). Do not shake or freeze. Discard unused portions. Administer reconstituted solution within 48 hours.

Drug Administration

Drug Interaction :
¨ Interactions possible with concomitant administration of psychotropic drugs.
¨ Increased toxicity noted with nephrotoxic (aminoglyco-sides, indomethacin), myelotoxic (chemotherapy), cardiotoxic (doxorubicin), or hepatotoxic drugs (methotrexate, asparaginase).
¨ Decreased effectiveness with concomitant administration of glucocorticoids.
¨ Increased hypotensive effects with concomitant administration of antihypertensives.

Side Effects and Toxicities :
¨ Constitutional: Fever, chills, pain, fatigue, weakness, malaise, weight gain, weight loss, headache
¨ CNS: Mental status changes, dizziness, sensory dysfunction
¨ GI: Nausea, vomiting, diarrhea, stomatitis, anorexia, GI bleeding, dyspepsia, constipation
¨ GU: Oliguria, anuria, BUN and serum creatinine elevation, proteinuria, hematuria
¨ Hematologic: Elevated bilirubin, transaminase, and alkaline phosphatase, anemia, thrombocytopenia, leukopenia, coagulation disorders, leukocytosis, eosinophilia; hypomagnesemia, acidosis, hypocalcemia, hypophosphatemia, hypokalemia, hyperuricemia, hypoalbuminemia, hypoproteinemia
¨ Integumentary: Pruritus, erythema, rash, dry skin, ex-foliative dermatitis
¨ Musculoskeletal: Arthralgia, myalgia
¨ Pulmonary and cardiovascular: Congestion, dyspnea, pulmonary edema, respiratory failure, tachypnea, pleural effusion, wheezing; hypotension, sinus tachycardia, arrhythmias, bradycardia
¨ Other: Jaundice, edema, infection

Special Considerations
¨ Contraindicated in patients with known allergy to aldesleukin or any component of the product; abnormal thallium stress test or pulmonary function test results; or organ allografts. Contraindicated in patients who have experienced the following toxicities during a previous treatment: sustained ventricular tachycardia (more thanfive beats); cardiac rhythm disturbances not controlled by or unresponsive to management; recurrent chest pain with ECG changes, consistent with angina or myocardial in-farction; intubation required for more than 72 hours; pericardial tamponade; renal dysfunction requiring dialysis for more than 72 hours; coma or toxic psychosis lasting more than 48 hours; repetitive or difficult-to-control seizures; bowel ischemia or perforation; or GI bleeding requiring surgery.

¨ Patients should have normal cardiac, pulmonary, hepatic, and CNS function before start of treatment.
¨ Assess for capillary leak syndrome, characterized by hypotension, hypoperfusion, edema, and effusions. Frequently monitor blood pressure, pulse, mental status, weight, and urine output. May need to administer dopamine (1 to 5 mcg/kg/min) to patients with capillary leak syndrome.
¨ Obtain laboratory tests (CBC with differential, blood chemistries, including renal and liver function tests) before and daily during therapy. Obtain a baseline chest x-ray, pulmonary function test with arterial blood gases, and stress thallium study. Repeat studies during therapy when clinically indicated.
¨ If adverse events occur that require dosage modifications, withhold treatment rather than decreasing dosage.