Proleukin


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Related to Proleukin: Aldesleukin

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.

aldesleukin

(al-dess-loo-kin) ,

interleukin-2

(trade name),

IL-2

(trade name),

Proleukin

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: interleukins
Pregnancy Category: C

Indications

Management of metastatic renal cell carcinoma.

Action

Increases cellular immunity (noted as lymphocytosis and eosinophilia), increases the production of cytokines (including tumor necrosis factor, interleukin-1, and gamma interferon), and inhibits tumor growth.

Therapeutic effects

Regression of renal cell carcinoma.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Rapidly distributes to intravascular, extracellular space; 70% is taken up by the liver, kidneys, and lungs.
Metabolism and Excretion: Metabolized to amino acids by renal tubular cells.
Half-life: 85 min.

Time/action profile (tumor regression after completion of first course)

ROUTEONSETPEAKDURATION
IV4 wkunknown12 mo

Contraindications/Precautions

Contraindicated in: Hypersensitivity to aldesleukin or mannitol; Cross-sensitivity to Escherichia coli—derived proteins may occur; History of cardiac or pulmonary disease as assessed by abnormal thallium stress testing or abnormal pulmonary function testing; Patients who have experienced any of the following toxicities during previous courses of aldesleukin—sustained ventricular tachycardia (≥5 beats), angina pectoris or MI as indicated by ECG changes, respiratory problems requiring more than 72 hr of intubation, pericardial tamponade, renal toxicity requiring more than 72 hr of dialysis, CNS dysfunction consisting of more than 48 hr of coma or psychosis, intractable seizures, bowel perforation or ischemia, GI bleeding requiring surgical intervention; Patients who have had allograft organ transplantation (↑ risk of rejection).
Use Cautiously in: History of cardiovascular, respiratory, hepatic, or renal disease; History of seizures or suspected CNS metastases (symptoms may be exaggerated and seizures may occur); Patients with child-bearing potential; Obstetric / Lactation / Pediatric: Safety not established.

Adverse Reactions/Side Effects

Respiratory

  • apnea (life-threatening)
  • respiratory failure (life-threatening)
  • dyspnea (most frequent)
  • pulmonary congestion (most frequent)
  • pulmonary edema (most frequent)
  • hemoptysis
  • pleural effusion
  • pneumothorax
  • tachypnea
  • wheezing

Cardiovascular

  • cardiac arrest (life-threatening)
  • HF (life-threatening)
  • MI (life-threatening)
  • stroke (life-threatening)
  • arrhythmias (most frequent)
  • hypotension (most frequent)
  • tachycardia (most frequent)
  • myocardial ischemia
  • pericardial effusion
  • thrombosis

Gastrointestinal

  • bowel perforation (life-threatening)
  • diarrhea (most frequent)
  • jaundice (most frequent)
  • nausea (most frequent)
  • stomatitis (most frequent)
  • vomiting (most frequent)
  • ascites
  • hepatomegaly

Genitourinary

  • oliguria/anuria (most frequent)
  • proteinuria (most frequent)
  • dysuria
  • hematuria
  • renal failure

Dermatologic

  • exfoliatative dermatitis (life-threatening)
  • pruritus (most frequent)

Fluid and Electrolyte

  • acidosis (most frequent)
  • hypocalcemia (most frequent)
  • hypokalemia (most frequent)
  • hypomagnesemia (most frequent)
  • hypophosphatemia (most frequent)
  • hyperkalemia
  • hyperuricemia
  • hyponatremia
  • metabolic alkalosis

Hematologic

  • anemia (most frequent)
  • coagulation disorders (most frequent)
  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)
  • eosinophilia
  • leukocytosis

Miscellaneous

  • capillary leak syndrome (life-threatening)
  • chills (most frequent)
  • fever (most frequent)
  • weight gain
  • weight loss

Interactions

Drug-Drug interaction

Corticosteroids decrease antineoplastic effectiveness. Avoid concurrent use with aldesleukin.Additive hypotension may occur with antihypertensives.Concurrent cardiotoxic, hepatotoxic, myelotoxic, or nephrotoxic drug therapy ↑ the risk of toxicity in these organs.

Route/Dosage

Intravenous (Adults) 600,000 IU/kg (0.037 mg/kg) every 8 hr for 14 doses. Cycle is repeated once after a 9-day rest period to a total of 28 doses. After a rest period of 7 wk, patients who have had a beneficial response may be evaluated for additional courses.

Availability

Powder for injection (requires reconstitution): 22 million units/vial

Nursing implications

Nursing assessment

  • Monitor ECG continuously during infusion. Cardiac function, including thallium stress testing, should be determined prior to initiation of therapy. Supraventricular arrhythmias may respond to digoxin or verapamil and usually resolve after completion of therapy.
  • Monitor vital signs at least daily throughout therapy. Fever, chills, rigors, and malaise usually occur within hours of administration. Acetaminophen and an NSAID, such as indomethacin, should be administered prior to initiation of aldesleukin therapy to reduce fever. Meperidine may be given to control rigors associated with fever.
  • Assess patient for the development of capillary leak syndrome (hypotension, hypovolemia, edema, ascites, pleural effusions). This initially manifests as a drop in arterial BP beginning 2–12 hr from start of administration. If BP decreases to <90 mmHg, constant ECG monitoring, hourly vital signs, and CVP monitoring are recommended.
  • Monitor respiratory status and pulse oximetry frequently. Pulmonary function tests, including arterial blood gases, and chest x-ray should be monitored prior to and periodically throughout therapy. Pulmonary toxicity (respiratory failure, tachypnea, wheezing) and pulmonary infiltration may become apparent by the 4th day of therapy and usually resolve within a few weeks after therapy. Respiratory failure may require intubation.
  • Monitor weight daily. Weight gain during therapy may be more than 10% of pretreatment weight. Reversal of weight gain, via diuresis of fluid, may take up to 1–2 wk after therapy.
  • Monitor for changes in mental status. Hold administration if patient develops moderate-to-severe lethargy or somnolence. Low doses of haloperidol have been used for debilitating mental status changes.
  • Assess frequently for signs of infection, particularly sepsis and bacterial endocarditis. Antibiotic prophylaxis directed against Staphylococcus aureus may be used for patients with central lines. Any intercurrent infections should be managed aggressively. Aldesleukin impairs the function of WBCs.
  • Assess for signs of anemia (increased fatigue, dyspnea, orthostatic hypotension) and bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis). Ranitidine or cimetidine may be given for prophylaxis of GI irritation and bleeding. Transfusions of RBCs and/or platelets may be required.
  • Assess nutrition and bowel status. Stomatitis may require a liquid diet or initiation of parenteral nutrition. Nausea, vomiting, and diarrhea occur in most patients and may lead to hypokalemia and acidosis. Antiemetics and antidiarrheals may be given as needed and are usually discontinued 12 hr after last dose.
  • Assess skin daily for rash or blisters on skin. Notify health care professional if these occur; exfoliative dermatitis can be fatal.
  • Lab Test Considerations: Monitor CBC, differential, platelet count, blood chemistries including electrolytes, and renal and hepatic function prior to and daily throughout therapy. May cause elevated bilirubin, BUN, serum creatinine, transaminase, and alkaline phosphatase levels. May cause anemia, thrombocytopenia, hypomagnesemia, acidosis, hypocalcemia, hypophosphatemia, hypokalemia, hyperuricemia, hypoalbuminemia, and hypoproteinemia.
    • Monitor thyroid function periodically during therapy.

Potential Nursing Diagnoses

Risk for infection (Side Effects)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • high alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations and infusion pump settings.
    • high alert: Aldesleukin should be administered only in a hospital setting with intensive care facilities.
  • Intravenous Administration
  • Intermittent Infusion: Reconstitute each vial with 1.2 mL of sterile water for injection. Concentration: 18 million IU (1.1 mg)/mL. Direct the sterile water at the side of the vial during reconstitution and swirl contents gently to prevent excessive foaming. Do not shake. Solution should be clear and colorless to slightly yellow. Administer within 48 hr of reconstitution. Discard unused portion.
    • Diluent: Dilute reconstituted dose in 50 mL of D5W. Do not reconstitute or dilute with bacteriostatic water for injection, 0.9% NaCl, or albumin.
    • Do not use an in-line filter during administration of aldesleukin.
  • Rate: Infuse each dose over 15 min.
  • Y-Site Compatibility: amikacin, amphotericin B colloidal, calcium gluconate, diphenhydramine,. fluconazole, foscarnet, gentamicin, magnesium sulfate, metoclopramide, morphine, ondansetron, ranitidine, tobramycin, trimethoprim/sulfamethoxazole, vancomycin
  • Y-Site Incompatibility: fluorouracil, ganciclovir, lorazepam, pentamidine, prochlorperazine, promethazine, rituximab, trastuzumab
  • Additive Incompatibility: Do not mix with other drugs.

Patient/Family Teaching

  • Instruct patient to notify health care professional if dyspnea, sore throat, fever, chills, yellow skin, unusual bleeding or bruising, or fatigue occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use a soft toothbrush and electric razor and to be especially careful to avoid falls. Patients should be cautioned not to drink alcohol or take medication containing aspirin or NSAIDs, because these may precipitate gastric bleeding.
  • Inform patient that visual problems usually begin shortly after aldesleukin administration and may persist for several weeks but are reversible.
  • Advise patient to use a nonhormonal method of contraception throughout therapy.

Evaluation/Desired Outcomes

  • Decrease in size or spread of renal cell carcinoma.

Proleukin®

Aldesleukin, IL-2 Immunology An agent used for metastatic kidney CA, melanoma, NHL, AML, TB, HIV infection, KS. See IL-2.

Proleukin

A brand name for ALDESLEUKIN.
References in periodicals archive ?
Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) Vanguard Group; ESPRIT Executive Committee.
A second study will compare the sequence of high dose Proleukin (aldesleukin) and 3mg/kg Ipilimumab immunotherapy in patients with metastatic melanoma.
th] at the 2015 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, investigators describe favorable safety results for Proleukin when administered after therapy directed against the cytotoxic T-lymphocyte antigen 4 (CTLA-4) or programmed cell death receptor-1 (PD-1) pathways.
In a presentation at the 51st annual meeting of the American Society of Clinical Oncology (ASCO), researchers presented updated survival data from the PROCLAIM mRCC retrospective cohort, along with new data from the mRCC prospective cohort, that confirm the benefits of administering Proleukin in the first-line setting, showing that careful patient selection and drug sequencing may yield better treatment outcomes.
At Novartis, he was responsible for the development of LBH589 (Panobinostat) for hematologic and oncologic indications, and was responsible for registration trials in the United States for CML, MM, and CTCL; lead development of post marketing trials for Proleukin (IL-2) in renal cell and melanoma; and lead development of RAD001 (Afinitor) for hematological indications.
The collective findings from the analyses suggest that Proleukin continues to play a significant role in improving patient outcomes when sequenced and perhaps combined with novel immunotherapeutic agents.
The market is currently driven by the use of the following immunomodulating agents: Schering-Plough's Intron A (interferon [IFN] alpha-2b), Roche's Roferon-A (IFN alpha-2a) and Novartis' Proleukin (aldesleukin); with new market entrants Bayer/Onyx Pharmaceuticals' Nexavar (sorafenib) and Pfizer's Sutent (sunitinib) making significant inroads into the market in 2006, their first year of sales.
ABX MA1, Alfanative , ALLOVECTIN-7, AP 12009, Avastin, BAY 504798, Canvaxin, Carboplatin, Carmustine, Ceplene Maxamine, Cisplatin, CP 4055, Dacarbazine, Dexosome, Didemnin B, Ecromeximab, Elea Vaccine, EMD 273063, Enhanzyn, F 50040, Genasense, GMK, GV 1001, GVAX, Iboctadekin, ILX 651, INGN 241, INO 1001, Intron A, Kahalalide F, Karenitecin, KOS 953, Lenalidomide, Lomeguatrib, MDX-010, Melacine, Melphalan, MJV 101, M-VAX, NOVOVAC-M1, NY-ESO-1 ISCOMS, Oncophage, OncoVax, OncoVEXGM-CSF, Paclitaxel, PD 0325901, Peginterferon alfa-2b, Pivanex, Proleukin , ProMune, QS-21, SB 249553, SB 715992, Sorafenib, Talabostat, Tamoxifen, Temozolomide, Temozolomide, Uvidem, Vinblastine/Vinorelbine, Virulizin, Vitaxin, Zadaxin
SITC Guidelines for Melanoma Treatment Include Proleukin by
The worldwide melanoma market size and sales data for Proleukin and Intron-A are also provided.
In a poster presentation entitled, "Improved Median Overall Survival (OS) in Patients with Metastatic Melanoma (mM) Treated with High Dose (HD) IL-2: Analysis of the PROCLAIM 2007-2012 National Registry," the PROCLAIM researchers presented an analysis of retrospective data from 170 patients with metastatic melanoma who received at least one dose of HD IL-2, which is marketed as Proleukin.