aldesleukin [IL-2] (Proleukin, Leukine)

Introduction

Tradename: Proleukin. (recombinant IL-2)

Indications

• metastatic renal cell carcinoma
  • response rate 14%
  • duration of response 20 months with some disease-free patients
• cutaneous melanoma
• Kaposi's sarcoma
• acute myeloid leukemia

Contraindications

• abnormal myocardial perfusion test
• abnormal pulmonary function test
• organ allograft
• tachyarrhymthmias
  • sustained premature ventricular contractions (> 5)
• uncontrolled cardiac arrhythmias
• myocardial ischemia
• intubation for > 72 hours
• pericardial tamponade
• renal dysfunction requiring dialysis for > 72 hours
• coma or toxic psychosis lasting > 48 hours
• repetitive or refractory seizures
• ischmic bowel, bowel perforation
• GI bleeding requiring surgery
• brain metastasis
• status epilepticus
  • • coma
    • organ transplantation
    • lactation Warnings:
• has been associated with capillary leak syndrome
• intensive therapy is associated with impaired neutrophil function (reduced chemotaxis)
  • increased risk of disseminated infection & endocarditis
  • pre-existing infection should be treated prior to initiation of therapy
• prophylactic antibiotics effective against S. aureus in patients with indwelling central catheters
• aggressive treatment of suspected or documented infection

Dosage

• 600,000 IU/kg IV every 8 hours for 14 doses, then repeat after 9 days Injectable: 22,000,000 IU/mL, 18,000,000 IU/mL when reconstituted

Pharmacokinetics

Elimination: 13 minutes

Adverse effects

• common (> 10%)
  • hypotension, dizziness, sensory dysfunction, sinus tachycardia, arrhythmias, pulmonary congestion, pruritus, erythema, dry skin, exfoliative dermatitis, rash, nausea/vomiting, fever/chills, pain, fatigue, weakness, malaise, edema, weight gain, diarrhea, stomatitis, anorexia, GI bleeding, anemia, thrombocytopenia, leukopenia, coagulation disorders, elevated liver function tests, elevated renal function tests hypomagnesemia, acidosis, hypocalcemia, hypophosphatemia, mental status changes, dyspnea, pulmonary edema, jaundice, oliguria, anuria, proteinuria
• less common (1-10%)
  • bradycardia, premature ventricular contractions (PVCs), myocardial ischemia*, myocardial infarction*, cardiac arrest*, respiratory failure, tachypnea, wheezing, ascites, leukocytosis, eosinophilia, hypokalemia, hypoproteinemia, hyponatremia, alkalosis, hypocholesterolemia, dyspepsia, constipation, sensory disorders, syncope, hematuria, renal impairment, purpura, arthralgia, myalgia, weight loss, injection site reactions
• uncommon (< 1%)
  • pancreatitis, hypothyroidism, coma, seizures, urinary frequency, alopecia, arthritis, muscle spasm, allergic reactions, congestive heart failure*, hypercalcemia
• other - capillary leak syndrome (CLS)

* heart failure from previous cardiomyopathy, myocarditis, or myocardial infarction occuring during treatment

Drug interactions

• corticosteroids may decrease toxicity of aldesleukin, but may decrease its effectiveness thus are not used in combination
• agents that increase aldesleukin toxicity
  • psychotropic drugs - narcotics, analgesics, antiemetics, sedatives, tranquilizers
  • nephrotoxic agents - aminoglycosides, indomethacin
  • myelotoxic agents - cytotoxic chemotherapeutic agents
  • hepatotoxic agents - methotrexate, asparaginase
• beta blockers & other hypotensive agents may potentiate hypotensive effects of aldesleukin

• drug interaction(s) of methotrexate with biological response modifier

More general terms

• antineoplastic immunomodulator
• interleukin-2; IL-2; T-cell growth factor; TCGF (IL2)

Additional terms

• capillary leak syndrome (CLS)