IL-2


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Related to IL-2: IL-2 receptor

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.

IL-2

abbreviation for interleukin-2.

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.

IL-2

Aldesleukin, IL-2, T-cell growth factor Immunology An immunomodulating biological response modifier produced at low baseline levels by CD4 T cells; after antigen presentation by antigen-presenting cells in presence of
IL-1, T cell production of IL-2 and IL-2 receptor–IL-2Rβ on membrane ↑, peaks at 6 hrs and falls to baseline levels; IL-2 is also produced by medullary thymocytes and a subset of large granular lymphocytes–NK cell activators; IL-2 up-regulates the immune system, causing lymphokine-activated killer–LAK cells to lyse tumor cells, see IL-2/LAK cells Therapeutics Recombinant IL-2 has been used for various conditions, including metastatic renal cell CA Adverse effects IL-2 therapy requires wks of intensive care due to toxic effects, including a 'capillary leakage syndrome. ', malaise, gastritis, GI symptoms, anemia, thrombocytopenia, rigors, chills, fever, hypotension, azotemia, jaundice, hyperbilirubinemia, rash–erythroderma globalis, confusion, ascites, fluid retention, pruritus, agitation, respiratory insufficiency, cardiac failure, irreversible demyelinization and hypothyroidism. See IL-2/LAK cells.
References in periodicals archive ?
In ESPRIT, people taking IL-2 had 466 serious complications (such as psychiatric and vein-related problems), while people not taking IL-2 had 383 serious complications.
All of these questions about the competency of CD4 T cells increased with IL-2 therapy could just as well be asked of CD4 T cell count increases realized with anti-HIV therapy.
CTCL is the first of several IL-2 receptor-expressing cancers for which we intend to evaluate the clinical efficacy of IL-2 Fusion Toxin," says Homer L.
Any error to gamma means you can't make any response to IL-2, IL-4, and IL-7.
An analysis of the intent-to-treat population demonstrates that treatment with Ceplene plus IL-2 prolonged the leukemia-free survival of patients with AML in remission compared to patients receiving the standard of care, no treatment.
The cytokines have been implicated as mediators of "capillary leak syndrome," which limits dose levels of IL-2 in RCC and MM patients.
Glenn Rice, director of the Cell Biology Division of Cell Therapeutics, the proprietary compound CT-2576 was described as blocking breakdown of gly-PI and subsequent formation of a unique myristylated phosphatic acid (mPA) species in IL-2 induced mouse cytotoxic T-cell clone CT6, suggesting that mPA is a necessary signaling lipid involved in IL-2 activation of T cells.
In the M01 Phase 3 trial, the incidences of treatment-emergent serious adverse events were comparable among patients treated with the Ceplene/IL-2 combination and those receiving IL-2 alone.
This is the third clinical trial of Ceplene in which I have participated over the last six years, and my personal observation is that the combination of Ceplene and IL-2 appears to be safe and well-tolerated by patients," said Dr.
One of the limiting factors for IL-2 therapy for human cancer is the toxic side effects that are associated with its use.
The M0103 trial allowed the inclusion of patients that had failed any prior treatment, including previous treatment with IL-2 and/or bio-chemotherapy, both of which were excluded from the M01 trial.