interleukin-2


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Related to interleukin-2: Proleukin

aldesleukin (interleukin-2, IL-2)

Proleukin

Pharmacologic class: Interleukin-2 (IL-2), human recombinant (cytokine)

Therapeutic class: Antineoplastic (miscellaneous)

Pregnancy risk category C

FDA Box Warning

• Give only to patients with normal cardiac and pulmonary function, as shown by thallium stress testing and pulmonary function testing. Use extreme caution when giving to patients with normal thallium stress test and normal pulmonary function tests who have a history of cardiac or pulmonary disease.

• Give under supervision of physician experienced in cancer chemotherapy, in setting where intensive care facilities and cardiopulmonary or intensive care specialists are available.

• Drug is linked to capillary leak syndrome, which causes hypotension and reduced organ perfusion (possibly severe and resulting in death).

• Before starting drug, preexisting bacterial infections must be treated, because drug may impair neutrophil function and increase disseminated infection risk. Patients with indwelling central lines are at special risk for infection with gram-positive microorganisms. Prophylactic antibiotics can help prevent staphylococcal infections.

• Withhold drug in patients who develop moderate to severe lethargy or somnolence; continued administration may cause coma.

Action

Activates cellular immunity and inhibits tumor growth by increasing lymphocytes and cytokines, which lyse tumor cells

Availability

Injection: 22 million international units/vial

Indications and dosages

Metastatic renal cell carcinoma and metastatic melanoma

Adults older than age 18: 600,000 international units/kg I.V. given over 15 minutes q 8 hours for a maximum of 14 doses, followed by 9 days of rest. Repeat for another 14 doses, for a maximum of 28 doses per course.

Off-label uses

• Colorectal cancer

• Kaposi's sarcoma

• Non-Hodgkin's lymphoma

Contraindications

• Hypersensitivity to drug

• Arrhythmias, cardiac tamponade, seizures, severe GI bleeding, coma or toxic psychosis lasting more than 48 hours

• Organ allograft

• Abnormal thallium stress test or pulmonary function test results

Precautions

Use cautiously in:

• anemia, bacterial infections, heart disease, CNS metastases, hepatic disease, pulmonary disease, renal disease, thrombocytopenia

• pregnant or breastfeeding patients

• children.

Administration

• Make sure patient's thallium stress test and pulmonary function test results are normal before giving.

Don't give if patient is drowsy or severely lethargic; contact prescriber immediately.

• Reconstitute drug according to label directions with 1.2 ml of sterile water for injection by injecting diluent against side of vial (to prevent excessive foaming).

• Further dilute reconstituted dose with 50 ml of 5% dextrose injection.

• Administer I.V. infusion over 15 minutes.

• Don't use in-line filter.

Adverse reactions

CNS: dizziness, mental status changes, syncope, sensory or motor dysfunction, headache, fatigue, rigors, weakness, malaise, poor memory, depression, sleep disturbances, hallucinations

CV: bradycardia, sinus tachycardia, premature atrial complexes, premature ventricular contractions, arrhythmias, myocardial ischemia, cardiac arrest, capillary leak syndrome and severe hypotension, myocardial infarction EENT: reversible vision changes, conjunctivitis

GI: nausea, vomiting, diarrhea, constipation, dyspepsia, abdominal pain, stomatitis, anorexia, intestinal perforation, ileus, GI bleeding

GU: hematuria, proteinuria, dysuria, renal failure, oliguria or anuria Hematologic: anemia, purpura, eosinophilia, thrombocytopenia, coagulation disorders, leukopenia, leukocytosis

Hepatic: jaundice, ascites

Metabolic: hyperglycemia, hypoglycemia, acidosis, alkalosis

Musculoskeletal: joint and back pain, myalgia

Respiratory: cough, chest pain, tachypnea, wheezing, dyspnea, pulmonary congestion, pulmonary edema, respiratory failure, apnea, pleural effusion

Skin: erythema, pruritus, rash, dry skin, petechiae, urticaria, exfoliative dermatitis

Other: weight gain or loss, fever, chills, edema, infection, pain or reaction at injection site, hypersensitivity reaction

Interactions

Drug-drug. Aminoglycosides, asparaginase, cytotoxic chemotherapy agents, doxorubicin, indomethacin, methotrexate: increased toxicity

Antihypertensives: increased hypotensive effect

Glucocorticoids: reduced antitumor effects

Drug-diagnostic tests. Alkaline phosphatase, bilirubin, glucose, blood urea nitrogen, creatinine, potassium, transaminases: increased levels

Calcium, glucose, magnesium, phosphorus, potassium, protein sodium, uric acid: decreased levels

Patient monitoring

• Monitor heart rate and rhythm, vital signs, and fluid intake and output.

• Assess for signs and symptoms of hypersensitivity reaction and infection.

• Monitor for adverse CNS effects. Report these immediately.

• Evaluate chest X-rays.

• Monitor CBC, electrolyte levels, and liver and kidney function test results.

Patient teaching

Tell patient that drug lowers resistance to infections. Advise him to immediately report fever, cough, breathing problems, and other signs or symptoms of infection.

Advise patient to immediately report chest pain, irregular or fast heart beats, easy bruising or bleeding, or abdominal pain.

• Instruct patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.

• Provide dietary counseling. Refer patient to dietitian if adverse GI effects significantly limit food intake.

• Notify patient that he'll undergo blood testing and have chest X-rays taken during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

in·ter·leu·kin-·2

(in'tĕr-lū'kin),
A cytokine derived from T-helper lymphocytes that causes proliferation of T lymphocytes and activated B lymphocytes; maintains long-term culturs of T cells.

interleukin-2

(ĭn′tər-lo͞o′kĭn-to͞o′)
n.
A cytokine that is released by T cells in response to an antigen and that regulates the growth and differentiation of B cells, monocytes, and many types of T cells. It has been used experimentally to treat cancer.

IL2

A gene on chromosome 4q26-q27 that encodes interleukin-2, a cytokine secreted by T cells in response to antigenic or mitogenic stimulation that plays a central role in the proliferation of T and B lymphocytes. IL-2 upregulates B-cells, monocytes, lymphokine-activated killer cells, natural killer cells and glioma cells.

in·ter·leu·kin-2

(in'tĕr-lū'kin)
A cytokine derived from T-helper lymphocytes that causes proliferation of T lymphocytes and activated B lymphocytes.

interleukin-2

A peptide chemical mediator released by helper T LYMPHOCYTES that stimulates clonal T cell and B cell division and proliferation. It is known as the T cell growth factor and is responsible for the activation on natural killer T cells.

in·ter·leu·kin-2

(in'tĕr-lū'kin)
A cytokine derived from T-helper lymphocytes that causes proliferation of T lymphocytes and activated B lymphocytes.
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Low-dose interleukin-2 treatment selectively modulates CD4(+) T cell subsets in patients with systemic lupus erythematosus.
All 11 patients had a 100% complete response rate from this three-drug combination (interleukin-2, imiquimod, vitamin A).
"The biology of interleukin-2," Annual Review of Immunology, 26: 453-479.
Treatment of acute graft-versus-host disease with humanized anti-Tc: an antibody that binds to the interleukin-2 receptor.
Adoptive immunotherapy for stage IV renal cell carcinoma: a novel protocol utilizing periodate and interleukin-2-activated autologous leukocytes and continuous infusions of low-dose interleukin-2. Am J Med.
ALKS 4230 is an engineered fusion protein designed to preferentially bind and signal through the intermediate affinity interleukin-2 receptor complex, thereby selectively activating and increasing the number of immunostimulatory tumor-killing immune cells while avoiding the expansion of immunosuppressive cells that interfere with anti-tumor response.
The method can also potentially include the use of a cytokine, such as interleukin-2, interleukin-12, or gamma-interferon, said Immunomedics president and CEO Cynthia L.
The latter report also links to MS a variant form of another gene, which encodes interleukin-2 receptor alpha.
Then, at the 1998 World AIDS Conference in Geneva, Roberto Arduino, MD, a young and energetic academic from Houston, delivered a lecture at a National Institutes of Health (NIH) meeting on the use of interleukin-2 for the treatment of HIV.
Further, following a "deep dive" on immuno-oncology candidate ALKS 4230, Amin believes preclinical data suggest the drug may be weaker on efficacy than Nektar Therapeutics' (NKTR) interleukin-2 receptor NKTR-214.
The team also provided the patients with interleukin-2, a compound that induces T cell growth.