Skip to main content

Aldesleukin (Monograph)

Brand name: Proleukin
Drug class: Antineoplastic Agents
- Cytokines
- Biologic Response Modifiers
VA class: AN900
Chemical name: 125-l-Serine-2-133-Interleukin 2 (human reduced)
Molecular formula: C690H1115N177O203S6
CAS number: 110942-02-4

Medically reviewed by Drugs.com on Sep 21, 2023. Written by ASHP.

Warning

    Cardiac and Pulmonary Function

  • Use only in patients with normal cardiac and pulmonary function as defined by thallium stress testing and pulmonary function tests.1 Use with extreme caution in patients with histories of cardiac or pulmonary disease even if thallium stress and pulmonary function test results are normal.1 (See Toxicity and Adequate Patient Monitoring under Cautions.)

    Experience of Supervising Clinician

  • Use in hospital setting under supervision of a qualified clinician experienced in therapy with antineoplastic agents.1 Use only when an intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine are available in case aldesleukin-induced toxicities develop.1

    Capillary Leak Syndrome

  • Risk of developing capillary leak syndrome (CLS); characterized by a loss of vascular tone and extravasation of plasma proteins and fluid into extravascular space.1 Results in hypotension and reduced organ perfusion; may be severe or fatal.1 CLS may be associated with cardiac arrhythmias (supraventricular and ventricular), angina, MI, respiratory insufficiency requiring intubation, GI bleeding or infarction, renal insufficiency, edema, and mental status changes.1 (See Capillary Leak Syndrome under Cautions.)

    Infections

  • Possible impaired neutrophil function (reduced chemotaxis) and increased risk of disseminated infection, including sepsis and bacterial endocarditis.1 Treat preexisting bacterial infections prior to initiation of therapy.1 Patients with indwelling central lines are at a higher risk for gram-positive bacterial infections.1 6 15 Prophylaxis with oxacillin, nafcillin, ciprofloxacin, or vancomycin associated with a reduced incidence of staphylococcal infections.1

    CNS Effects

  • Withhold administration if moderate-to-severe lethargy or somnolence develops; continued administration may result in coma.1 (See CNS Effects under Cautions.)

Introduction

Antineoplastic and immunomodulating agent; human interleukin-2 (IL-2) derivative and biosynthetic (recombinant DNA origin) cytokine (i.e., lymphokine).1 2

Uses for Aldesleukin

Renal Cell Cancer

Treatment of metastatic renal cell carcinoma in selected patients, alone1 22 109 111 116 117 144 or in combination1 5 22 with surgery144 or other drug therapies, such as biologic response modifiers (e.g., interferon alfa), 37 42 43 44 45 46 49 53 115 117 119 120 121 122 123 124 125 126 136 138 161 or adoptive immunotherapy (e.g., lymphokine-activated killer [LAK] cells, tumor-infiltrating lymphocytes [TILs]).26 27 29 30 31 32 37 38 47 48 49 51 98 105 127 128 156

There is no generally accepted standard therapy for metastatic renal cell carcinoma.22 52 64 109

Despite initial response to aldesleukin, tumor relapse is common, particularly following partial response.113 Treatment of relapsed disease with the same aldesleukin-based therapy is rarely effective,113 114 but some secondary responses observed in patients receiving a different aldesleukin-based regimen.113

Melanoma

Palliative treatment of metastatic melanoma in selected patients, alone and in combination with other agents1 5 68 including biologic response modifiers (e.g., interferon alfa),43 53 55 79 80 81 173 adoptive immunotherapy (e.g., LAK cells, TILs),30 31 47 51 65 66 70 71 74 75 76 78 and/or conventional chemotherapeutic agents (e.g., cisplatin, dacarbazine).68 82 171 172

Although higher response rates with some combination regimens,15 52 65 68 85 100 101 172 176 improvement in survival not demonstrated and toxicity often is greater.30 52 65 66 81 101 171 172 174 175 176

Despite initial response to aldesleukin, tumor relapse is common in patients with metastatic melanoma, particularly following partial response.113 Treatment of relapsed disease with the same aldesleukin-based therapy that produced the initial response rarely is effective,113 114 but some secondary responses observed in patients receiving a different aldesleukin-based regimen.113

Aldesleukin Dosage and Administration

General

Administration

Administer by IV infusion.1 3

Also administered by sub-Q injection† [off-label].15 22 40 55

IV Administration

For solution and drug compatibility information see Compatibility under Stability.

Allow solution to reach room temperature prior to IV infusion.1

Use plastic (PVC) containers for more consistent delivery; drug may adhere to glass.1 52

Do not use an inline filter.1 101

Do not coadminister with other drugs in the same container.1

Consult manufacturer and/or specialized references for instructions on preparation of solutions administered by continuous IV infusion† [off-label] or sub-Q administration† [off-label].101

Reconstitution

Reconstitute vial containing 22 million units (1.3 mg) of the drug with 1.2 mL of sterile water for injection to provide a solution containing 18 million units (1.1 mg)/mL.1

Direct sterile water for injection toward the side of the vial with gentle swirling to avoid excessive foaming of the solution; do not shake.1

Dilution

Add appropriate reconstituted dose to 50 mL of 5% dextrose injection.1 101

Solutions outside the range of 30–70 mcg/mL may result in increased variability in drug delivery; avoid use of such solutions for short-duration IV infusions.1 101 Manufacturer states that a larger or smaller volume of 5% dextrose injection may be used to maintain a concentration of 30–70 mcg/mL.1 101

Rate of Administration

Administer over 15 minutes.1 101

Dosage

Potency usually is expressed in international units (IU);1 3 because other units also have been reported (e.g., Cetus Units [CU], Roche Units [RU], Biologic Response Modifiers Program Units [BRMPU]) and are not equivalent (e.g., 1 RU = 3 IU, 1 CU = 6 IU), exercise care in interpreting published dosages and concentrations.3 101

International units are stated as units rather than as IU to minimize medication errors that could result from misinterpretation of written orders employing IU.b

When a vial containing 22 million units is reconstituted by adding 1.2 mL of sterile water for injection, each mL contains 18 million units of aldesleukin (equivalent to 1.1 mg of drug).1

Optimum dosage and regimen for treatment of metastatic renal cell carcinoma15 31 34 39 40 49 52 54 55 99 101 103 111 116 143 or metastatic melanoma not established.15 52 66 101 170

Administration of doses in excess of recommended dose associated with a more rapid onset of anticipated dose-limiting toxicities.1

Tumor regression has continued for up to 12 months after 1 or more courses of therapy, but optimum duration of therapy not yet established.1 3

Consult manufacturer and/or specialized references for instructions on alternative dosages administered by continuous IV infusion† [off-label] or sub-q injection† [off-label].101

Adults

Renal Cell Cancer
Intermittent IV Infusion

600,000 units/kg over 15 minutes every 8 hours for 14 doses (5-day treatment cycle), followed by a 9-day rest period, and a second 5-day treatment cycle (600,000 units/kg over 15 minutes every 8 hours for 14 doses) for a maximum of 28 doses or until intolerable adverse effects develop.1 23 38 52 111 (See Dosage Modification for Toxicity and Contraindications for Retreatment under Dosage and Administration.)

Alternatively, some clinicians have used 720,000 units/kg over 15 minutes every 8 hours for a maximum of 15 doses per cycle, with a 10-day rest period between the 2 cycles.20 31

Manufacturer recommends drug-free interval ≥7 weeks between treatment courses from date of previous hospital discharge;1 however, some clinicians report using shorter rest periods (i.e., 2–4 weeks) between courses.52

Evaluate patients approximately 4 weeks after completion of initial course of therapy and again immediately prior to scheduled start of next course.1 Manufacturer states that further therapy with aldesleukin should be undertaken only if there is evidence of tumor regression following the last course and the patient has not developed serious toxicity that would contraindicate continuation.1 Some clinicians believe stabilization of disease in absence of serious toxicity warrants continued therapy.52 101

Continuous IV Infusion†

18 million units/m2 daily for two 5-day cycles, with a drug-free interval of 5–8 days between cycles.15 32 35 36 37 38 97 115 119

Sub-Q Injection†

18 million units daily for 5 days followed by a 2-day rest period.15 40 For additional cycles, 9 million units on days 1 and 2, followed by 18 million units daily for the next 3 days.15 40 52 101 Treatment cycles of 6 consecutive weeks separated by a 3-week drug-free period were used.40

Melanoma
IV Infusion

600,000 units/kg over 15 minutes every 8 hours for 14 doses (5-day treatment cycle), followed by a 6- to 9-day rest period, then a second 5-day treatment cycle (600,000 units/kg over 15 minutes every 8 hours for 14 doses) for a maximum of 28 doses per course or until intolerable adverse effects develop.1 170

Alternatively, some clinicians have used 720,000 units/kg over 15 minutes every 8 hours for a maximum of 15 doses per cycle, with a 10-day rest period between the 2 cycles.20 31

Manufacturer recommends drug-free interval ≥7 weeks between treatment courses from date of previous hospital discharge;1 however, some clinicians report using rest periods of 6–12 weeks between courses.170

Evaluate patients approximately 4 weeks after completion of initial course of therapy and again immediately prior to scheduled start of next course.1 Manufacturer states that further therapy with aldesleukin should be undertaken only if there is evidence of tumor regression following the last course and the patient has not developed serious toxicity that would contraindicate continuation.1 Some clinicians believe stabilization of disease in absence of serious toxicity warrants continued aldesleukin therapy.52 101

Dosage Modification for Toxicity and Contraindications for Retreatment
Contraindications for Retreatment1 52

Retreatment is contraindicated in patients who have experienced the following toxicities:1

Cardiovascular:

Sustained ventricular tachycardia (≥5 beats)

Cardiac rhythm disturbances, not controlled or unresponsive to management

Chest pain with ECG changes, consistent with angina or MI

GI:

Bowel ischemia/perforation

GI bleeding requiring surgery

Neurologic:

Coma or toxic psychosis lasting >48 hours

Repetitive or difficult-to-control seizures

Cardiac tamponade

Respiratory:

Intubation for >72 hours

Renal:

Renal failure requiring dialysis for >72 hours
Therapy Interruptions for Toxicity

Toxicities requiring dosage modification should involve withholding or interrupting a dose rather than reducing the individual dose to be given.1

Therapy Interruptions for Toxicity Based on Manifestations

Toxicity

Hold dose for:

May give subsequent dose if:

Cardiovascular

Atrial fibrillation, supraventricular tachycardia, recurrent or persistent bradycardia or bradycardia requiring treatment1

Asymptomatic with complete recovery to normal sinus rhythm1

SBP <90 mm Hg with increasing vasopressor requirements1

SBP ≥90 mm Hg and stable or improving vasopressor requirement 1

ECG changes consistent with MI, ischemia, or myocarditis, with or without chest pain, or suspicion of cardiac ischemia1

Asymptomatic; MI and myocarditis ruled out; minimal clinical suspicion of angina; or no evidence of ventricular hypokinesia1

Dermatologic

Bullous dermatitis or marked worsening of preexisting skin condition; avoid topical corticosteroid therapy1

All signs of bullous dermatitis resolved1

GI

GI bleeding demonstrated by stool guaiac test repeatedly positive with a result >3+ or 4+1

Negative stool guaiac test results1

Hepatic

Signs of hepatic failure, including encephalopathy, increasing ascites, liver pain, or hypoglycemia1

When all signs of hepatic failure have resolved; initiate a new course of treatment (if warranted) ≥7 weeks after cessation of adverse events and hospital discharge1

Infectious complications

Sepsis syndrome occurs and patient is clinically unstable1

Sepsis syndrome resolved, patient is clinically stable and infection is being treated1

Neurologic

Changes in mental status (e.g., moderate confusion, agitation)1

Mental status changes completely resolved1

Renal

Scr ≥4.5 mg/dL or ≥4 mg/dL in presence of severe volume overload, acidosis, or hyperkalemia1

Scr <4 mg/dL and stable fluid and electrolyte status1

Persistent oliguria with urine output <10 mL/hour for 16–24 hours with increasing Scr1

Urine output >10 mL/hour with a decrease in Scr of >1.5 mg/dL or normalization of Scr1

Respiratory

Oxygen saturation <90%1

Oxygen saturation ≥90%1

Prescribing Limits

Adults

Renal Cell Carcinoma or Melanoma
IV Infusion

Maximum 28 doses per course.1

Special Populations

No special population dosage recommendations at this time.1 Manufacturer states patients should have normal cardiac, pulmonary, hepatic, and CNS function at the start of therapy.1 (See Patient Selection, CNS Effects, Hepatic Impairment, Renal Impairment, and Geriatric Use, all under Cautions.)

Detailed Aldesleukin dosage information

Cautions for Aldesleukin

Contraindications

Warnings/Precautions

Warnings

Patient Selection

Careful patient selection mandatory prior to initiation of drug, including assessment of cardiac, renal, hepatic, CNS, and pulmonary functions, blood chemistry, and blood cell counts.1 (See Boxed Warning and also see Toxicity and Adequate Patient Monitoring under Cautions.)

However, even patients with normal cardiovascular, pulmonary, hepatic, and CNS function may experience adverse events.1 Adverse effects are frequent, often serious, and sometimes fatal.1 6 15 20 Carefully weigh risks versus benefits of therapy.1 15 6 20 (See Contraindications under Cautions.)

Patients with favorable Eastern Cooperative Oncology Group performance status (ECOG PS 0) at treatment initiation have a higher response rate and lower toxicity; therefore, consider performance status during patient selection for treatment.1 111 112 Experience in patients with ECOG PS >1 extremely limited.1

Autoimmune and Inflammatory Reactions

Possible development or exacerbation of autoimmune disease and inflammatory disorders when used alone or in combination with interferon alfa.1 (See Specific Drugs under Interactions.)

Possible onset of symptomatic hyperglycemia and/or diabetes mellitus.1

Possible hypothyroidism, sometimes preceded by hyperthyroidism, following treatment; may require thyroid hormone replacement therapy.1 Hyperthyroidism also reported.1

Increased risk of allograft rejection in transplant patients because of enhanced cellular immune function.1

Exacerbation of Crohn’s disease, scleroderma, thyroiditis, inflammatory arthritis, diabetes mellitus, oculo-bulbar myasthenia gravis, crescentic IgA glomerulonephritis, cholecystitis, cerebral vasculitis, Stevens-Johnson syndrome, and bullous pemphigoid reported.1

CNS Effects

Thoroughly evaluate and treat all patients for CNS metastases; must have a negative CT scan prior to receiving therapy.1

New neurologic manifestations (e.g., mental status changes, speech difficulties, cortical blindness, limb/gait ataxia, hallucinations, agitation, obtundation, coma) and anatomic lesions reported following aldesleukin therapy in patients without evidence of CNS metastases.1 6 8 9 15 20

Mental status changes (e.g., irritability, confusion, depression, agitation, lethargy, somnolence) may be a direct result of CNS toxicity from aldesleukin or indicative of bacteremia, early bacterial sepsis, hypoperfusion, or occult CNS malignancy.1 Aldesleukin-induced mental status changes generally reverse within several days after discontinuance of the drug,15 although may progress for several days before recovery begins.1 15 101 However, permanent neurologic defects reported.1

Potential for seizures; use with extreme caution if known seizure disorders.1

Sensitivity Reactions

Risk of anaphylaxis in patients receiving various treatment regimens that included aldesleukin.1

Hypersensitivity reactions (e.g., erythema, pruritus, hypotension) reported within hours of administration of therapy in patients receiving combination regimens with sequential administration of high-dose aldesleukin and antineoplastic agents (specifically cisplatin, dacarbazine, tamoxifen, and interferon alfa);1 medical intervention required in some patients.1 (See Specific Drugs under Interactions.)

Potential for nonanaphylactic allergic reactions.140

May predispose individuals to acute, atypical adverse reactions to iodinated radiographic contrast media.1 (See Specific Drugs under Interactions.)

Major Toxicities

Capillary Leak Syndrome

Risk of CLS particularly at usual dosages recommended by the manufacturer; risk of severe, possibly fatal, hypotension and reduced organ perfusion.1 6 8 11 15 101 Begins immediately after treatment initiation; characterized by increased vascular permeability to proteins and fluids and reduced vascular tone.1 6 15 (See Boxed Warning.)

Monitor fluid and organ perfusion status carefully; frequently monitor BP, heart rate, and organ function, including assessment of mental status and urine output.1 Assess hypovolemia by catheterization and central venous pressure monitoring.1

If hypovolemia occurs, administration of IV fluids (e.g., colloid replacement fluids or crystalloids) recommended.1 Use caution when administering large volumes of IV fluids to correct hypovolemia; unrestrained fluid administration may exacerbate complications associated with edema or effusions.1

Use extreme caution when treating patients with fixed requirements for large volumes of fluid (e.g., those with hypercalcemia); flexibility in fluid and vasopressor management is essential for maintaining organ perfusion and BP.1 101

Management of edema and ascites and/or effusions depends on careful balancing of fluid shifts to ensure that the consequences of hypovolemia (e.g., impaired organ perfusion) or fluid accumulation (e.g., pulmonary edema) do not exceed the patient’s tolerance.1

Early administration of IV dopamine with or without IV phenylephrine hydrochloride before onset of hypotension can help maintain organ perfusion, particularly renal perfusion, and preserve urine output.1 Exercise caution; prolonged use of vasopressors, alone or in combination, at relatively high doses may be associated with cardiac rhythm disturbances.1

If adequate organ perfusion not maintained (demonstrated by altered mental status, reduced urine output, decrease in SBP to <90 mm Hg, or onset of cardiac arrhythmias), withhold subsequent aldesleukin doses until organ perfusion recovers and SBP ≥90 mm Hg.1

Recovery from CLS begins within a few hours after discontinuance of aldesleukin therapy.1 If excessive weight gain, edema or pulmonary congestion with shortness of breath occurs, diuretics may hasten recovery once BP normalized.1

Flu-like Syndrome

Flu-like syndrome (e.g., fever [sometimes grade 4 or life-threatening], chills, rigors) possible.1 6 13 15 Other symptoms possible (e.g., pain,1 abdominal pain,1 malaise,1 asthenia, 1 arthralgia and/or myalgia, 15 140 chest pain,140 back pain,140 fatigue).140

General Precautions

Toxicity and Adequate Patient Monitoring

Highly toxic drug; prior to initiation of therapy and daily during therapy, perform hematologic tests (e.g., CBC, differential, platelet counts), blood chemistries (e.g., serum electrolyte concentrations), renal and hepatic function tests, and chest radiographs.1 (See Cardiovascular Effects, Pulmonary Effects, Renal Impairment, and Hepatic Impairment, all under Cautions.)

During therapy, monitor vital signs (i.e., temperature, pulse, BP, respiration rate) at least every 4 hours52 and patient’s weight and fluid intake and output daily.1 52 In hypotensive patients, monitor vital signs hourly.1 If SBP decreases (especially to <90 mm Hg), perform constant cardiac rhythm monitoring.1 (See Cardiovascular Effects under Cautions.)

Cardiovascular Effects

Prior to initiation of therapy, perform a stress thallium study to document normal cardiac ejection fraction and unimpaired myocardial wall motion.1 101 If results suggest minor wall motion abnormalities, test further to exclude CAD.1 (See Boxed Warning.)

During therapy, assess cardiac function daily.1 If signs or symptoms (e.g., chest pain, murmurs, gallops, irregular cardiac rhythm, palpitation), assess with an ECG and cardiac enzymes.1 Evidence of myocardial injury, including findings compatible with MI or myocarditis, reported.1 Ventricular hypokinesia caused by myocarditis may persist for several months.1 If evidence of cardiac ischemia or CHF, withhold therapy and repeat thallium study.1

Pulmonary Effects

Perform baseline pulmonary function tests with arterial blood gases in all patients.1 Must have adequate pulmonary function (FEV1 >2 L or >75% of predicted value based on height and age) prior to initiation of therapy.1

Monitor pulmonary function regularly during therapy.1 If dyspnea or clinical signs of respiratory impairment (i.e., tachypnea or rales), assess with arterial blood gases.1 Repeat as often as clinically indicated.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether aldesleukin is distributed into milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1

Geriatric Use

Response, median number of doses per course, and median number of courses of therapy in patients ≥65 years of age does not appear to differ from that in younger adults; however, possible increased risk of toxicity in patients with renal impairment.1 Possible increased incidence of severe urogenital toxicity and dyspnea compared with younger patients.1

Hepatic Impairment

Aldesleukin therapy impairs hepatic function.1 Normal hepatic function necessary at start of therapy.1 (See Toxicity and Adequate Patient Monitoring under Cautions and also see Hepatotoxic Agents under Interactions.)

Renal Impairment

Contraindicated in patients who develop renal impairment requiring dialysis for >72 hours after a previous course of aldesleukin.1

Aldesleukin therapy impairs renal function.1 Preexisting renal impairment appears to be associated with an increased risk of more severe and prolonged renal dysfunction.10 15 (See Toxicity and Adequate Patient Monitoring under Cautions and also see Nephrotoxic Agents under Interactions.)

Manufacturer states that Scr should be≤1.5 mg/dL prior to initiation of aldesleukin therapy.1

Common Adverse Effects

Hypotension, diarrhea, renal dysfunction with oliguria, chills, vomiting, dyspnea, rash, bilirubinemia, thrombocytopenia, nausea, confusion, increased Scr, anemia, fever, peripheral edema, malaise, lung disorders (e.g., pulmonary congestion, rales, rhonchi), pruritus, asthenia, tachycardia, increased AST, stomatitis, somnolence, anorexia.1

Life-threatening or grade 4 adverse effects: Renal dysfunction with oliguria/anuria, hypotension, respiratory disorder (i.e., ARDS, respiratory failure, intubation), coma, bilirubinemia.1

Drug Interactions

Cardiotoxic Agents

Concurrent administration may increase risk of cardiotoxicity.1

CNS-Active Agents

Concurrent administration may increase risk of CNS effects.1

Hepatotoxic Agents

Concurrent administration may increase risk of hepatotoxicity. (See Hepatic Impairment under Cautions.)1

Myelotoxic Agents

Concurrent administration may increase risk of myelotoxicity.1

Nephrotoxic Agents

Concurrent administration may increase risk of nephrotoxicity. (See Renal Impairment under Cautions.)1

Specific Drugs

Drug

Interaction

Comments

Aminoglycosides

Possible increase in nephrotoxicity1

Anthracyclines (e.g., doxorubicin)

Possible increase in cardiotoxicity1

Antihypertensive agents (e.g., β-blocking agents)

Possible increase in hypotensive effects1

Antineoplastic agents

Possible increased myelotoxicity1

Safety and efficacy not established1

Asparaginase

Possible increase in hepatotoxicity1

Cisplatin

Potential hypersensitivity reactions (erythema, pruritus, and hypotension)1

Medical intervention may be required1

CNS depressants (e.g., analgesics, antiemetics, opiate agonists, sedatives, tranquilizers)

Possible increased risk of CNS effects1

Corticosteroids (glucocorticoids)

Possible reduction of antitumor effectiveness1

Avoid concomitant use1

Dacarbazine

Potential hypersensitivity reactions (erythema, pruritus, and hypotension)1

Medical intervention may be required1

Indomethacin

Possible increase in nephrotoxicity1

Interferon alfa

Possible development or exacerbation of autoimmune disease and inflammatory disorders (e.g., thyroiditis,1 inflammatory arthritis,1 oculo-bulbar myasthenia gravis,1 crescentic IgA glomerulonephritis,1 155 Stevens-Johnson syndrome,1 or bullous pemphigoid)1

Possible increased incidence of myocardial injury (MI,1 myocarditis,1 ventricular hypokinesia,1 and severe rhabdomyolysis)1

Potential hypersensitivity reactions (erythema, pruritus, and hypotension)1

Medical intervention may be required1

Methotrexate

Possible increase in hepatotoxicity1

Roentgenographic agents

Potential acute, atypical adverse reactions (e.g., fever, chills, nausea, vomiting, diarrhea, pruritus, rash, hypotension, edema, oliguria)1 to iodinated radiographic contrast media 1

May occur when contrast media are administered up to several months after aldesleukin administration1

Tamoxifen

Potential hypersensitivity reactions (erythema, pruritus, and hypotension)1

Medical intervention may be required1
Aldesleukin drug interactions (more detail)

Aldesleukin Pharmacokinetics

Absorption

Bioavailability

Approximately 30% of a dose detectable in plasma upon completion of IV infusion.1

Distribution

Extent

Rapidly distributed into extravascular space; animal studies indicate rapid (<1 minute) uptake into lung, liver, kidney, and spleen.1

Not known whether aldesleukin is distributed into milk.1

Elimination

Metabolism

Metabolized principally in the kidney.1

Elimination Route

Excreted in urine; little or no active drug detected.1

Half-life

85 minutes.1

Stability

Storage

Parenteral

Powder for Injection

Store in carton at 2–8°C until used; protect from light.1

Preferably, store reconstituted or diluted solution at 2–8°C.1 Alternatively, store at room temperature for ≤48 hours.1 Do not freeze.1

Compatibility

Parenteral

Solution Compatibility

Compatible1

Dextrose 5% in water

Sterile water for injection

Incompatible1

Bacteriostatic water for injection

Sodium chloride 0.9%
Drug Compatibility
Y-Site Compatibilitya

Compatible

Amikacin sulfate

Amphotericin B

Calcium gluconate

Co-trimoxazole

Diphenhydramine HCl

Fat emulsion, IV

Fluconazole

Foscarnet sodium

Gentamicin sulfate

Magnesium sulfate

Metoclopramide HCl

Morphine sulfate

Ondansetron HCl

Variable

Ranitidine HCI

Thiethylperazine malate

Tobramycin

Vancomycin

Incompatible

Fluorouracil

Ganciclovir sodium

Lorazepam

Pentamidine isethionate

Prochlorperazine edisylate

Promethazine HCl

Variable

Dopamine HCl

Heparin sodium

Potassium chloride

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Aldesleukin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

22 million units

Proleukin

Novartis

AHFS DI Essentials™. © Copyright 2024, Selected Revisions October 1, 2009. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Novartis. Proleukin (aldesleukin) for injection prescribing information. Emeryville, CA; 2008 Oct.

2. Kintzel PE, Calis KA. Recombinant interleukin-2: a biological response modifier. Cain Pharm. 1991; 10:110-28.

3. Cetus Oncology Corporation, Emeryville, CA: Personal communication.

4. Fleeger CA, ed. USAN 1993: USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1992:23.

5. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52. http://www.ncbi.nlm.nih.gov/pubmed/15529105?dopt=AbstractPlus

6. Siegel JP, Puri RK. Interleukin-2 toxicity. J Clin Oncol. 1991; 9:694-704. http://www.ncbi.nlm.nih.gov/pubmed/2066765?dopt=AbstractPlus

7. Eberlein TJ, Schoof DD, Michie HR et al. Ibuprofen causes reduced toxic effects of interleukin 2 administration in patients with metastatic cancer. Arch Surg. 1989; 124:542-7. http://www.ncbi.nlm.nih.gov/pubmed/2785376?dopt=AbstractPlus

8. Nora R, Abrams JS, Tait NS et al. Myocardial toxic effects during recombinant interleukin-2 therapy. J Natl Cancer Inst. 1989; 81:59-63. http://www.ncbi.nlm.nih.gov/pubmed/2783257?dopt=AbstractPlus

9. Denicoff KD, Rubinow DR, Papa MZ et al. The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med. 1987; 107:293-300. http://www.ncbi.nlm.nih.gov/pubmed/3497595?dopt=AbstractPlus

10. Belldegrun A, Webb DE, Austin HA III et al. Effects of interleukin-2 on renal function in patients receiving immunotherapy for advanced cancer. Ann Intern Med. 1987; 106:817-22. http://www.ncbi.nlm.nih.gov/pubmed/3495213?dopt=AbstractPlus

11. Webb DE, Austin HA III, Belldegrun A et al. Metabolic and renal effects of interleukin-2 immunotherapy for metastatic cancer. Clin Nephrol. 1988; 30:141-5. http://www.ncbi.nlm.nih.gov/pubmed/3263237?dopt=AbstractPlus

12. Sparano JA, Brandt LJ, Dutcher JP et al. Symptomatic exacerbation of Crohn disease after treatment with high-dose interleukin-2. Ann Intern Med. 1993; 118:617-8. http://www.ncbi.nlm.nih.gov/pubmed/8452327?dopt=AbstractPlus

13. Fisher B, Keenan AM, Garr BS et al. Interleukin-2 induces profound reversible cholestasis: a detailed analysis in treated cancer patients. J Clin Oncol. 1989; 7: 1852-62.

14. Gaspari AA, Lotze MT, Rosenberg SA et al. Dermatologic changes associated with interleukin 2 administration. JAMA. 1987; 258:1624-9. http://www.ncbi.nlm.nih.gov/pubmed/3306005?dopt=AbstractPlus

15. Whittington R, Faulds D. Interleukin-2: a review of its pharmacological properties and therapeutic use in patients with cancer. Drugs. 1993; 46:446-514. http://www.ncbi.nlm.nih.gov/pubmed/7693434?dopt=AbstractPlus

16. Lee RE, Gaspari MA, Lotze MT et al. Interleukin 2 and psoriasis. Arch Dermatol. 1988: 124;1811-5.

17. Pockaj BA, Topalian SL, Steinberg SM et al. Infectious complications associated with interleukin-2 administration: a retrospective review of 935 treatment courses. J Clin Oncol. 1993; 22:136-47.

18. Marcus SL, Dutcher JP, Paietta E et al. Severe hypovitaminosis C occurring as a result of adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer cells. Cancer Res. 1987; 47:4208-12. http://www.ncbi.nlm.nih.gov/pubmed/3496958?dopt=AbstractPlus

19. Yagoda A, Petrylak D, Thompson S. Cytotoxic chemotherapy for advanced renal carcinoma. Urol Clin North Am. 1993; 20:303-21. http://www.ncbi.nlm.nih.gov/pubmed/8493752?dopt=AbstractPlus

20. Rosenberg SA, Yang JC, Topalian SL et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994; 271:907-13. http://www.ncbi.nlm.nih.gov/pubmed/8120958?dopt=AbstractPlus

21. Hellman S. Immunotherapy for metastatic cancer: establishing a “proof of principle.” JAMA. 1994; 271:945-6. Editorial. (IDIS 327069)

22. Renal cell cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2008 May 22.

23. Abrams JS, Rayner AA, Peter H et al. High-dose recombinant interleukin-2 alone: a regimen with limited activity in the treatment of advanced renal cell carcinoma. J Natl Cancer Inst. 1990; 82:1202-6. http://www.ncbi.nlm.nih.gov/pubmed/2194036?dopt=AbstractPlus

24. Poo WJ, Fynan T, Davis C et al. High-dose recombinant interleukin-2 alone in patients with metastatic renal cell carcinoma. Proc Annu Meet Am Soc Clin Oncol. 1991; 10:A557.

25. Rosenberg SA, Lotze MT, Muul LM et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985; 313:1485-92. http://www.ncbi.nlm.nih.gov/pubmed/3903508?dopt=AbstractPlus

26. Fisher RI, Coltman CA Jr, Doroshow JH et al. Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells: a phase II clinical trial. Ann Intern Med. 1988; 108:518-23. http://www.ncbi.nlm.nih.gov/pubmed/3258138?dopt=AbstractPlus

27. Rosenberg SA, Lotze MT, Muul LM et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med. 1987; 316:889-97. http://www.ncbi.nlm.nih.gov/pubmed/3493432?dopt=AbstractPlus

28. Negrier S, Philip T, Stoter G et al. Interleukin-2 with or without LAK cells in metastatic renal cell carcinoma: a report of a European multicentre study. Eur J Cancer Clin Oncol. 1989; 25(Suppl 3):S21-8.

29. Law TM, Motzer RJ, Mazumdar M et al. Phase III randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma. Cancer. 1995; 76:824-32. http://www.ncbi.nlm.nih.gov/pubmed/8625186?dopt=AbstractPlus

30. McCabe MS, Stablein D, Hawkins MJ. The modified group C experience: phase III randomized trials of IL-2 vs IL-2/LAK in advanced renal cell carcinoma and advanced melanoma. Proc Annu Meet Am Soc Clin Oncol. 1991; 10:A714.

31. Rosenberg SA, Lotze MT, Yang JC et al. Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst. 1993; 85:622-32. http://www.ncbi.nlm.nih.gov/pubmed/8468720?dopt=AbstractPlus

32. West WH, Tauer KW, Yannelli JR et al. Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. N Engl J Med. 1987; 316:898-905. http://www.ncbi.nlm.nih.gov/pubmed/3493433?dopt=AbstractPlus

33. Gaynor ER, Weiss GR, Margolin KA et al. Phase I study of high-dose continuous-infusion recombinant interleukin-2 and autologous lymphokine-activated killer cells in patients with metastatic or unresectable malignant melanoma and renal cell carcinoma. J Natl Cancer Inst. 1990; 82:1397-1402. http://www.ncbi.nlm.nih.gov/pubmed/2388289?dopt=AbstractPlus

34. Parkinson DR. Interleukin-2: further progress through greater understanding. J Natl Cancer Inst. 1990; 82:1374-6. http://www.ncbi.nlm.nih.gov/pubmed/2388286?dopt=AbstractPlus

35. von der Maase H, Geertsen P, Thatcher N et al. Recombinant interleukin-2 in metastatic renal cell carcinoma—a European multicentre phase II study. Eur J Cancer. 1991; 27:1583-9. http://www.ncbi.nlm.nih.gov/pubmed/1782066?dopt=AbstractPlus

36. Dillman RO, Oldham RK, Tauer KW et al. Continuous interleukin-2 and lymphokine-activated killer cells for advanced cancer: a National Biotherapy Study Group trial. J Clin Oncol. 1991; 9:1233-40. http://www.ncbi.nlm.nih.gov/pubmed/2045864?dopt=AbstractPlus

37. Dillman RO, Church C, Oldham RK et al. Inpatient continuous-infusion interleukin-2 in 788 patients with cancer: the National Biotherapy Study Group experience. Cancer. 1993; 71:2358-70. http://www.ncbi.nlm.nih.gov/pubmed/8453558?dopt=AbstractPlus

38. Weiss GR, Margolin KA, Aronson FR et al. A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma. J Clin Oncol. 1992; 10:275-81. http://www.ncbi.nlm.nih.gov/pubmed/1732429?dopt=AbstractPlus

39. Lopez M, Carpano S, Cancrini A et al. Phase II study of continuous intravenous infusion of recombinant interleukin-2 in patients with advanced renal cell carcinoma. Ann Oncol. 1993; 4:689-91. http://www.ncbi.nlm.nih.gov/pubmed/8241001?dopt=AbstractPlus

40. Sleijfer DT, Janssen RAJ, Buter J et al. Phase II study of subcutaneous interleukin-2 in unselected patients with advanced renal cell cancer on an outpatient basis. J Clin Oncol. 1992; 10:1119-23. http://www.ncbi.nlm.nih.gov/pubmed/1607917?dopt=AbstractPlus

41. Dutcher JP, Fisher RI, Weiss G et al. An outpatient (OPT) regimen of subcutaneous (sc) interleukin-2 (IL2) plus alpha-interferon (IFN) in metastatic renal cell cancer (RCC). Proc Annu Meet Am Soc Clin Oncol. 1993; 12:A778.

42. Figlin RA, Belldegrun A, Moldawer N et al. Concomitant administration of recombinant human interleukin-2 and recombinant interferon alfa-2A: an active outpatient regimen in metastatic renal cell carcinoma. J Clin Oncol. 1992; 10:414-21. http://www.ncbi.nlm.nih.gov/pubmed/1482425?dopt=AbstractPlus

43. Oldham RK, Blumenschein G, Schwartzberg L et al. Combination biotherapy utilizing interleukin-2 and alpha interferon in patients with advanced cancer: a National Biotherapy Study Group trial. Mol Biother. 1992; 4:4-9. http://www.ncbi.nlm.nih.gov/pubmed/1627272?dopt=AbstractPlus

44. Ilson DH, Motzer RJ, Kradin RL et al. A phase II trial of interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma. J Clin Oncol. 1992; 10: 1124-30. http://www.ncbi.nlm.nih.gov/pubmed/1607918?dopt=AbstractPlus

45. Lipton A, Harvey H, Givant E et al. Interleukin-2 and interferon-α-2a outpatient therapy for metastatic renal cell carcinoma. J Immunother. 1993; 13:122-9.

46. Atkins MB, Sparano J, Fisher RI et al. Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma. J Clin Oncol. 1993; 11:661-70. http://www.ncbi.nlm.nih.gov/pubmed/8478661?dopt=AbstractPlus

47. Kradin RL, Kurnick JT, Lazarus DS et al. Tumour-infiltrating lymphocytes and interleukin-2 in the treatment of advanced cancer. Lancet. 1989; 1:577-80. http://www.ncbi.nlm.nih.gov/pubmed/2564111?dopt=AbstractPlus

48. Bukowski RM, Sharfman W, Murthy S et al. Clinical results and characterization of tumor-infiltrating lymphocytes with or without recombinant interleukin 2 in human metastatic renal cell carcinoma. Cancer Res. 1991; 51:4199-205. http://www.ncbi.nlm.nih.gov/pubmed/1868441?dopt=AbstractPlus

49. Bukowski RM, McLain D, Olencki T et al. Interleukin-2: use in solid tumors. Stem Cells. 1993; 11:26-32. http://www.ncbi.nlm.nih.gov/pubmed/8457777?dopt=AbstractPlus

50. Atzpodien J, Kirchner H, Lopez Hanninen E et al. Alpha-interferon, interleukin-2 and 5-fluorouracil as a promising biochemotherapy regimen for the management of advanced renal cell carcinoma. Proc Annu Meet Am Soc Clin Oncol. 1993; 12:A708.

51. Rosenberg SA, Lotze MT, Yang JC et al. Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg. 1989; 210:474-85. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1357927&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/2679456?dopt=AbstractPlus

52. Reviewers’ comments (personal observations).

53. Rosenberg SA, Lotze MT, Yang JC et al. Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. J Clin Oncol. 1989; 7:1863-74. http://www.ncbi.nlm.nih.gov/pubmed/2685181?dopt=AbstractPlus

54. Bukowski RM, Goodman P, Crawford ED et al. Phase II trial of high-dose intermittent interleukin-2 in metastatic renal cell carcinoma: a Southwest Oncology Group Study. J Natl Cancer Inst. 1990; 82:143-6. http://www.ncbi.nlm.nih.gov/pubmed/2294224?dopt=AbstractPlus

55. Atzpodien J, Kirchner H. The outpatient use of recombinant human interleukin-2 and interferon alfa-2b in advanced malignancies. Eur J Cancer. 1991; 27(Suppl 4): S88-92. http://www.ncbi.nlm.nih.gov/pubmed/1799491?dopt=AbstractPlus

56. Lotze MT, Chang AE, Seipp CA et al. High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer: responses, treatment-related morbidity, and histologic findings. JAMA. 1986; 256:3117-24. http://www.ncbi.nlm.nih.gov/pubmed/3491225?dopt=AbstractPlus

57. Kradin R, Kurnick J. Interleukin-2 therapy for disseminated cancer. JAMA. 1987; 257:1729. http://www.ncbi.nlm.nih.gov/pubmed/3493357?dopt=AbstractPlus

58. Mittelman A, Arlin ZA, Podack E. Interleukin-2 therapy for disseminated cancer. JAMA. 1987; 257:1729-30. http://www.ncbi.nlm.nih.gov/pubmed/3493357?dopt=AbstractPlus

59. Rosenfelt FP, Weinstein IM, Rosenbloom BE. Interleukin-2 therapy for disseminated cancer. JAMA. 1987; 257:1730.

60. Lotze MT, Rosenberg SA. Interleukin-2 therapy for disseminated cancer. JAMA. 1987; 257:1730-1.

61. Moertel CG. Interleukin-2 therapy for disseminated cancer. JAMA. 1987; 257:1731. http://www.ncbi.nlm.nih.gov/pubmed/3820489?dopt=AbstractPlus

62. Smith T. Interleukin-2 therapy for disseminated cancer. JAMA. 1987; 257:1731. http://www.ncbi.nlm.nih.gov/pubmed/3820489?dopt=AbstractPlus

63. Parkinson DR, Abrams JS, Wiernik PH et al. Interleukin-2 therapy in patients with metastatic malignant melanoma: a phase II study. J Clin Oncol. 1990; 8:1650-6. http://www.ncbi.nlm.nih.gov/pubmed/2213101?dopt=AbstractPlus

64. Linehan WM, Shipley WU, Parkinson DR. Cancer of the kidney and ureter. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 4th ed. Philadelphia: JB Lippincott Company; 1993:1023-51.

65. Balch CM, Houghton AN, Peters LJ. Cutaneous melanoma. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 4th ed. Philadelphia: JB Lippincott Company; 1993:1612-61.

66. Sznol M, Dutcher JP, Atkins MB et al. Review of interleukin-2 alone and interleukin-2/LAK clinical trials in metastatic malignant melanoma. Cancer Treat Rev. 1989; 16(Suppl A):29-38. http://www.ncbi.nlm.nih.gov/pubmed/2670213?dopt=AbstractPlus

67. Dutcher JP, Creekmore S, Weiss GR et al. A phase II study of interleukin-2 and lymphokine-activated killer cells in patients with metastatic malignant melanoma. J Clin Oncol. 1989; 7:477-85. http://www.ncbi.nlm.nih.gov/pubmed/2647913?dopt=AbstractPlus

68. Melanoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2008 May 22.

69. Dutcher JP, Gaynor ER, Boldt DH et al. A phase II study of high-dose continuous infusion interleukin-2 with lymphokine-activated killer cells in patients with metastatic melanoma. J Clin Oncol. 1991; 9:641-8. http://www.ncbi.nlm.nih.gov/pubmed/2066760?dopt=AbstractPlus

70. Topalian SL, Solomon D, Avis FP et al. Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J Clin Oncol. 1988; 6:839-53. http://www.ncbi.nlm.nih.gov/pubmed/3259261?dopt=AbstractPlus

71. Rosenberg SA, Packard BS, Aebersold PM et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma: a preliminary report. N Engl J Med. 1988; 319:1676-80. http://www.ncbi.nlm.nih.gov/pubmed/3264384?dopt=AbstractPlus

72. Sondel PM, Sosman JA, Hank JA et al. Tumor-infiltrating lymphocytes and interleukin-2 in melanomas. N Engl J Med. 1989; 320:1418-9. http://www.ncbi.nlm.nih.gov/pubmed/2785641?dopt=AbstractPlus

73. Rosenberg SA. Tumor-infiltrating lymphocytes and interleukin-2 in melanomas. N Engl J Med. 1989; 320:1419. http://www.ncbi.nlm.nih.gov/pubmed/2716790?dopt=AbstractPlus

74. Hanson JP, Kurtz J, Rohloff C et al. Recombinant interleukin-2 (rIL-2) with tumor-infiltrating lymphocytes (TIL) for metastatic malignant melanoma (MMM). Proc Annu Meet Am Soc Clin Oncol. 1993; 12:A1357.

75. Rosenberg SA, Yannelli JR, Yang JC et al. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst. 1994; 86:1159-66. http://www.ncbi.nlm.nih.gov/pubmed/8028037?dopt=AbstractPlus

76. Rosenberg SA, Aebersold P, Cornetta K et al. Gene transfer into humans—immunotherapy of patients with advanced melanoma using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med. 1990; 323: 570-8. http://www.ncbi.nlm.nih.gov/pubmed/2381442?dopt=AbstractPlus

77. Cournoyer D, Caskey CT. Gene transfer into humans: a first step. N Engl J Med. 1990; 323:601-3. http://www.ncbi.nlm.nih.gov/pubmed/2381445?dopt=AbstractPlus

78. Dillman RO, Oldham RK, Barth NM et al. Continuous interleukin-2 and tumor-infiltrating lymphocytes as treatment of advanced melanoma: a National Biotherapy Study Group trial. Cancer. 1991; 68:1-8. http://www.ncbi.nlm.nih.gov/pubmed/2049729?dopt=AbstractPlus

79. Castello G, Comella P, Manzo T et al. Immunological and clinical effects of intramuscular rIFNα-2a and low dose subcutaneous rIL-2 in patients with advanced malignant melanoma. Melanoma Res. 1993; 3:43-9. http://www.ncbi.nlm.nih.gov/pubmed/8471836?dopt=AbstractPlus

80. Keilholz U, Scheibenbogen C, Tilgen W et al. Interferon-α and interleukin-2 in the treatment of metastatic melanoma. Cancer. 1993; 72:607-14. http://www.ncbi.nlm.nih.gov/pubmed/8319195?dopt=AbstractPlus

81. Sparano JA, Fisher RI, Sunderland M et al. Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma. J Clin Oncol. 1993; 11:1969-77. http://www.ncbi.nlm.nih.gov/pubmed/8410122?dopt=AbstractPlus

82. Demchak PA, Mier JW, Robert NJ et al. Interleukin-2 and high-dose cisplatin in patients with metastatic melanoma: a pilot study. J Clin Oncol. 1991; 9:1821-30. http://www.ncbi.nlm.nih.gov/pubmed/1655988?dopt=AbstractPlus

83. Eisenthal A, Skornick Y, Chaitchik S. Combined chemotherapy and immunotherapy with low doses of interleukin-2 and interferon-alpha administered sc in advanced melanoma patients. Ann Oncol. 1992; 3(Suppl 5):141. http://www.ncbi.nlm.nih.gov/pubmed/1606084?dopt=AbstractPlus

84. Hamblin TJ, Davies B, Sadullah S et al. A phase II study of the treatment of metastatic malignant melanoma with a combination of dacarbazine, cisplatin, interleukin-2 (IL-2) and alfa-interferon (IFN). Proc Annu Meet Am Soc Clin Oncol. 1991; 10:A1029.

85. Richards JM, Mehta N, Ramming K et al. Sequential chemoimmunotherapy in the treatment of metastatic melanoma. J Clin Oncol. 1992; 10:1338-43. http://www.ncbi.nlm.nih.gov/pubmed/1634924?dopt=AbstractPlus

86. Flaherty LE, Robinson W, Redman BG et al. A phase II study of dacarbazine and cisplatin in combination with outpatient administered interleukin-2 in metastatic malignant melanoma. Cancer. 1993; 71:3520-5. http://www.ncbi.nlm.nih.gov/pubmed/8490900?dopt=AbstractPlus

87. Antoine E, Vuillemin E, Benhammouda A et al. Interleukin-2-alpha-interferon combined with cis-platinum therapy in metastatic malignant melanoma (MMM) patients: results of two consecutive trials. Proc Annu Meet Am Soc Clin Oncol. 1993; 12:A1321.

88. Khayat D, Borel C, Tourani JM et al. Sequential chemoimmunotherapy with cisplatin, interleukin-2, and interferon alfa-2a for metastatic melanoma. J Clin Oncol. 1993; 11:2173-80. http://www.ncbi.nlm.nih.gov/pubmed/8229131?dopt=AbstractPlus

89. Mitchell MS, Kempf RA, Harel W et al. Effectiveness and tolerability of low-dose cyclophosphamide and low-dose intravenous interleukin-2 in disseminated melanoma. J Clin Oncol. 1988; 6:409-24. http://www.ncbi.nlm.nih.gov/pubmed/2965219?dopt=AbstractPlus

90. Mitchell MS. Chemotherapy in combination with biomodulation: a 5-year experience with cyclophosphamide and interleukin-2. Semin Oncol. 1992; 19(Suppl 4):80-7. http://www.ncbi.nlm.nih.gov/pubmed/1553579?dopt=AbstractPlus

91. Flaherty LE, Redman BG, Chabot GG et al. A phase I-II study of dacarbazine in combination with outpatient interleukin-2 in metastatic malignant melanoma. Cancer. 1990; 65:2471-7. http://www.ncbi.nlm.nih.gov/pubmed/2337862?dopt=AbstractPlus

92. Dillman RO, Oldham RK, Barth NM et al. Recombinant interleukin-2 and adoptive immunotherapy alternated with dacarbazine therapy in melanoma: a National Biotherapy Study Group trial. J Natl Cancer Inst. 1990; 82:1345-9. http://www.ncbi.nlm.nih.gov/pubmed/2199682?dopt=AbstractPlus

93. Stoter G, Aamdal S, Rodenhuis S et al. Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma: a multicenter phase II study. J Clin Oncol. 1991; 9:1687-81. http://www.ncbi.nlm.nih.gov/pubmed/1875225?dopt=AbstractPlus

94. Belli F, Arienti F, Rivoltini L et al. Treatment of recurrent in transit metastases from cutaneous melanoma by isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine activated killer cells: a pilot study. Melanoma Res. 1992; 2:263-71. http://www.ncbi.nlm.nih.gov/pubmed/1490114?dopt=AbstractPlus

95. Arienti F, Belli F, Longoni P et al. Treatment of recurrent in transit metastases from cutaneous melanoma by normothermic isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine-activated killer cells. Proc Annu Meet Am Assoc Cancer Res. 1993; 34:A2799.

96. Chiron Therapeutics. Proleukin (aldesleukin for injection): product information for American Hospital Formulary Service. Emeryville, CA: 1992 May 5.

97. Geersten PR, Hermann GG, von der Maase H et al. Treatment of metastatic renal cell carcinoma by continuous intravenous infusion of recombinant interleukin-2: a single-center phase II study. J Clin Oncol. 1992; 10:753-9. http://www.ncbi.nlm.nih.gov/pubmed/1569448?dopt=AbstractPlus

98. Thompson JA, Shulman KL, Benyunes MC et al. Prolonged continuous intravenous infusion interleukin-2 and lymphokine-activated killer-cell therapy for metastatic renal cell carcinoma. J Clin Oncol. 1992; 10:960-8. http://www.ncbi.nlm.nih.gov/pubmed/1588376?dopt=AbstractPlus

99. Stahl M, Wilke HJ, Seeber S et al. Cytokines and cytotoxic agents in renal cell carcinoma: a review. Semin Oncol. 1992; 19(Suppl 4):70-9. http://www.ncbi.nlm.nih.gov/pubmed/1553577?dopt=AbstractPlus

100. Aapro MS. Advances in systemic treatment of malignant melanoma. Eur J Cancer. 1993; 29A:613-7. http://www.ncbi.nlm.nih.gov/pubmed/8435218?dopt=AbstractPlus

101. Chiron Therapeutics. Emeryville, CA: Personal communication.

102. Sella A, Zukiwski A, Robinson E et al. Interleukin-2 (IL-2) with interferon-alfa (IFN-alpha) and 5-fluorouracil (5-FU) in patients (pts) with metastatic renal cell cancer (RCC). Proc Annu Meet Am Soc Clin Oncol. 1994; 13:A733.

103. Yang JC, Sherry RM, Steinberg SM et al. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003; 21:3127-32. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2275327&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/12915604?dopt=AbstractPlus

104. Mitchell MS, Kempf RA, Harel W et al. Low-dose cyclophosphamide and low-dose interleukin-2 for malignant melanoma. Bull NY Acad Med. 1989; 65:128-44.

105. Palmer PA, Vinke J, Evers P et al. Continuous infusion of recombinant interleukin-2 with or without autologous lymphokine activated killer cells for the treatment of advanced renal cell carcinoma. Eur J Cancer. 1992; 28A:1038-44. http://www.ncbi.nlm.nih.gov/pubmed/1627369?dopt=AbstractPlus

106. Legha SS, Buzaid AC. Role of recombinant interleukin-2 in combination with interferon-alfa and chemotherapy in the treatment of advanced melanoma. Semin Oncol. 1993; 20(Suppl 9):27-32. http://www.ncbi.nlm.nih.gov/pubmed/8054006?dopt=AbstractPlus

107. Blair S, Flaherty L, Valdivieso M et al. Comparison of high-dose interleukin-2 (HD IL-2) with combined chemotherapy/low-dose IL-2 (CHEMO/IL-2) in metastatic malignant melanoma (MMM). Proc Annu Meet Am Soc Clin Oncol. 1991; 10:A1031.

108. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to June 28, 1996. Rockville, MD; 1996 Jul.

109. Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med. 1996; 335:865-75. http://www.ncbi.nlm.nih.gov/pubmed/8778606?dopt=AbstractPlus

110. NCCN practice guidelines for kidney cancer. National Comprehensive Cancer Network. Oncology (Huntingt). 1998; 12:396-412.

111. Fyfe G, Fisher RI, Rosenberg SA et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995; 13:688-96. http://www.ncbi.nlm.nih.gov/pubmed/7884429?dopt=AbstractPlus

112. Lissoni P, Barni S, Ardizzoia A et al. Prognostic factors of the clinical response to subcutaneous immunotherapy with interleukin-2 alone in patients with metastatic renal cell carcinoma. Oncology. 1994; 51:59-62. http://www.ncbi.nlm.nih.gov/pubmed/8265104?dopt=AbstractPlus

113. Lee DS, White DE, Hurst R et al. Patterns of relapse and response to retreatment in patients with metastatic melanoma or renal cell carcinoma who responded to interleukin-2-based immunotherapy. Cancer J Sci Am. 1998; 4:86-93. http://www.ncbi.nlm.nih.gov/pubmed/9532410?dopt=AbstractPlus

114. Sherry RM, Rosenberg SA, Yang JC. Relapse after response to interleukin-2-based immunotherapy: patterns of progression and response to retreatment. J Immunother. 1991; 10:371-5. http://www.ncbi.nlm.nih.gov/pubmed/1790145?dopt=AbstractPlus

115. Negrier S, Escudier B, Lasset C et al. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Francais d’Immunotherapie. N Engl J Med. 1998; 338:1272-8. http://www.ncbi.nlm.nih.gov/pubmed/9562581?dopt=AbstractPlus

116. Figlin RA. Renal cell carcinoma: management of advanced disease. J Urol. 1999; 161:381-7. http://www.ncbi.nlm.nih.gov/pubmed/9915408?dopt=AbstractPlus

117. Bukowski RM. Natural history and therapy of metastatic renal cell carcinoma: the role of interleukin-2. Cancer. 1997; 80:1198-220. http://www.ncbi.nlm.nih.gov/pubmed/9317170?dopt=AbstractPlus

118. Yang JC, Rosenberg SA. An ongoing prospective randomized comparison of interleukin-2 regimens for the treatment of metastatic renal cell cancer. Cancer J Sci Am. 1997; 3(Suppl 1):S79-84. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2597550&blobtype=pdf

119. Palmer PA, Atzpodien J, Philip T et al. A comparison of 2 modes of administration of recombinant interleukin-2: continuous intravenous infusion alone versus subcutaneous administration plus interferon alpha in patients with advanced renal cell carcinoma. Cancer Biother. 1993; 8:123-36. http://www.ncbi.nlm.nih.gov/pubmed/7804353?dopt=AbstractPlus

120. Atzpodien J, Lopez Hanninen E, Kirchner H et al. Multiinstitutional home-therapy trial of recombinant human interleukin-2 and interferon alfa-2 in progressive metastatic renal cell carcinoma. J Clin Oncol. 1995; 13:497-501. http://www.ncbi.nlm.nih.gov/pubmed/7844611?dopt=AbstractPlus

121. Lopez Hanninen E, Kirchner H, Atzpodien J. Interleukin-2 based home therapy of metastatic renal cell carcinoma: risks and benefits in 215 consecutive single institution patients. J Urol. 1996; 155:19-25. http://www.ncbi.nlm.nih.gov/pubmed/7490829?dopt=AbstractPlus

122. Vogelzang NJ, Lipton A, Figlin RA. Subcutaneous interleukin-2 plus interferon alfa-2a in metastatic renal cancer: an outpatient multicenter trial. J Clin Oncol. 1993; 11:1809-16. http://www.ncbi.nlm.nih.gov/pubmed/8355047?dopt=AbstractPlus

123. Lissoni P, Barni S, Ardizzoia A et al. A randomized study of low-dose interleukin-2 subcutaneous immunotherapy versus interleukin-2 plus interferon-alpha as first line therapy for metastatic renal cell carcinoma. Tumori. 1993; 79:397-400. http://www.ncbi.nlm.nih.gov/pubmed/8171738?dopt=AbstractPlus

124. Boccardo F, Rubagotti A, Canobbio L et al. Interleukin-2, interferon-alpha and interleukin-2 plus interferon-alpha in renal cell carcinoma. A randomized phase II trial. Tumori. 1998; 84:534-9. http://www.ncbi.nlm.nih.gov/pubmed/9862512?dopt=AbstractPlus

125. Jayson GC, Middleton M, Lee SM et al. A randomized phase II trial of interleukin 2 and interleukin 2-interferon alpha in advanced renal cancer. Br J Cancer. 1998; 78:366-9. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2063040&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/9703284?dopt=AbstractPlus

126. Witte RS, Leong T, Ernstoff MS et al. A phase II study of interleukin-2 with and without beta-interferon in the treatment of advanced renal cell carcinoma. Invest New Drugs. 1995; 13:241-7. http://www.ncbi.nlm.nih.gov/pubmed/8729953?dopt=AbstractPlus

127. Figlin RA, Pierce WC, Kaboo R et al. Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2 and cytokine-primed or CD8(+) selected tumor infiltrating lymphocytes from primary tumor. J Urol. 1997; 158:740-5. http://www.ncbi.nlm.nih.gov/pubmed/9258071?dopt=AbstractPlus

128. Belldegrun A, Pierce W, Kaboo R et al. Interferon-alpha primed tumor-infiltrating lymphocytes combined with interleukin-2 and interferon-alpha as therapy for metastatic renal cell carcinoma. J Urol. 1993; 150:1384-90. http://www.ncbi.nlm.nih.gov/pubmed/8411405?dopt=AbstractPlus

129. Ellerhorst JA, Sella A, Amato RJ et al. Phase II trial of 5-fluorouracil, interferon-alpha and continuous infusion interleukin-2 for patients with metastatic renal cell carcinoma. Cancer. 1997; 80:2128-32. http://www.ncbi.nlm.nih.gov/pubmed/9392335?dopt=AbstractPlus

130. Ravaud A, Audhuy B, Gomez F et al. Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastatic renal cell carcinoma: a multicenter phase II trial. Groupe Francais d’Immunotherapie. J Clin Oncol. 1998; 16:2728-32. http://www.ncbi.nlm.nih.gov/pubmed/9704724?dopt=AbstractPlus

131. Tourani JM, Pfister C, Berdah JF et al. Outpatient treatment with subcutaneous interleukin-2 and interferon alfa administration in combination with fluorouracil in patients with metastatic renal cell carcinoma: results of a sequential nonrandomized phase II study. Subcutaneous Administration Propeukin Program Cooperative Group. J Clin Oncol. 1998; 16:2505-13. http://www.ncbi.nlm.nih.gov/pubmed/9667271?dopt=AbstractPlus

132. Dutcher JP, Atkins M, Fisher R et al. Interleukin-2-based therapy for metastatic renal cell cancer: the Cytokine Working Group experience, 1989-1997. Cancer J Sci Am. 1997; 3(Suppl 1):S73-8. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2597550&blobtype=pdf

133. Negrier S, Caty A, Lesimple T et al. Treatment of patients with metastatic renal carcinoma with a combination of subcutaneous interleukin-2 and interferon alfa with or without fluorouracil. Groupe Francais d'Immunotherapie, Federation Nationale des Centres de Lutte Contre le Cancer. J Clin Oncol. 2000; 18:4009-15. http://www.ncbi.nlm.nih.gov/pubmed/11118461?dopt=AbstractPlus

134. Gleave ME, Elhilali M, Fradet Y et al. Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group. N Engl J Med. 1998; 338:1265-71. http://www.ncbi.nlm.nih.gov/pubmed/9562580?dopt=AbstractPlus

135. Young RC. Metastatic renal-cell carcinoma: what causes occasional dramatic regressions? N Engl J Med. 1998; 338:1305-6. Editorial.

136. Henriksson R, Nilsson S, Colleen S et al. Survival in renal cell carcinoma-a randomized evaluation of tamoxifen vs interleukin 2, alpha-interferon (leucocyte) and tamoxifen. Br J Cancer. 1998; 77:1311-7. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2150170&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/9579838?dopt=AbstractPlus

137. Buter J, Sleijfer DT, van der Graaf WT et al. A progress report on the outpatient treatment of patients with advanced renal cell carcinoma using subcutaneous recombinant interleukin-2. Semin Oncol. 1993; 20(6 Suppl 9):16-21. http://www.ncbi.nlm.nih.gov/pubmed/8284687?dopt=AbstractPlus

138. Bergmann L, Fenchel K, Weidmann E et al. Daily alternating administration of high-dose alpha-2b-interferon and interleukin-2 bolus infusion in metastatic renal cell cancer. A phase II study. Cancer. 1993; 72:1733-42. http://www.ncbi.nlm.nih.gov/pubmed/8348502?dopt=AbstractPlus

139. Sherry RM, Pass HI, Rosenberg SA et al. Surgical resection of metastatic renal cell carcinoma and melanoma after response to interleukin-2-based immunotherapy. Cancer. 1992; 69:1850-5. http://www.ncbi.nlm.nih.gov/pubmed/1551067?dopt=AbstractPlus

140. Chiron Therapeutics. Proleukin (aldesleukin) for injection prescribing information. Emeryville, CA; 1994 May.

141. Redman BG, Flaherty L, Martino S et al. Effect of calcium replacement on the hemodynamic changes associated with high dose interleukin-2 therapy. Am J Clin Oncol. 1992; 15:340-3. http://www.ncbi.nlm.nih.gov/pubmed/1514532?dopt=AbstractPlus

142. Conant EF, Fox KR, Miller WT. Pulmonary edema as a complication of interleukin-2 therapy. AJR Am J Roentgenol. 1989; 152:749-52. http://www.ncbi.nlm.nih.gov/pubmed/2784257?dopt=AbstractPlus

143. Escudier B, Ravaud A, Fabbro M et al. High-dose interleukin-2 two days a week for metastatic renal cell carcinoma: a FNCLCC multicenter study. J Immunother Emphasis Tumor Immunol. 1994; 16:306-12. http://www.ncbi.nlm.nih.gov/pubmed/7881640?dopt=AbstractPlus

144. Vogelzang NJ, Stadler WM. Kidney cancer. Lancet. 1998; 352:1691-6. http://www.ncbi.nlm.nih.gov/pubmed/9853456?dopt=AbstractPlus

145. Schomburg A, Kirchner H, Fenner M et al. Lack of therapeutic efficacy of tamoxifen in advanced renal cell carcinoma. Eur J Cancer. 1993; 29A:737-40. http://www.ncbi.nlm.nih.gov/pubmed/7682428?dopt=AbstractPlus

146. Stahl M, Wilke H, Schmoll HJ et al. A phase II study of high dose tamoxifen in progressive, metastatic renal cell carcinoma. Ann Oncol. 1992; 3:167-8. http://www.ncbi.nlm.nih.gov/pubmed/1606089?dopt=AbstractPlus

147. Stahl M, Schmoll E, Becker H et al. Lonidamine versus high-dose tamoxifen in progressive, advanced renal cell carcinoma: results of an ongoing randomized phase II study. Semin Oncol. 1991; 18(2 Suppl 4):33-7. http://www.ncbi.nlm.nih.gov/pubmed/2031196?dopt=AbstractPlus

148. Hernberg M, Pyrhonen S, Muhonen T. Regimens with or without interferon-alpha as treatment for metastatic melanoma and renal cell carcinoma: an overview of randomized trials. J Immunother. 1999; 22:145-54. http://www.ncbi.nlm.nih.gov/pubmed/10093039?dopt=AbstractPlus

149. Minasian LM, Motzer RJ, Gluck L et al. Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol. 1993; 11:1368-75. http://www.ncbi.nlm.nih.gov/pubmed/8315435?dopt=AbstractPlus

150. Clark JI, Atkins MB, Urba WJ et al. Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell carcinoma: a Cytokine Working Group randomized trial. J Clin Oncol. 2003; 21:3133-40. http://www.ncbi.nlm.nih.gov/pubmed/12810695?dopt=AbstractPlus

151. Pizzocaro G, Piva L, Costa A et al. Adjuvant interferon (IFN) to radical nephrectomy in Robson’s stages II and III renal cell cancer (RCC), a multicenter randomized study with some biological evaluations. Proc Am Soc Clin Oncol. 1997; 16:A1132.

152. Trump DL, Elson P, Propert K et al. Randomized, controlled trial of adjuvant therapy with lymphoblastoid interferon (L-IFN) in resected, high-risk renal cell carcinoma (HR-RCC). Proc Am Soc Clin Oncol. 1996; 15:A648.

153. Galligioni E, Quaia M, Merlo A et al. Adjuvant immunotherapy treatment of renal carcinoma patients with autologous tumor cells and bacillus Calmette-Guerin: five-year results of a prospective randomized study. Cancer. 1996; 77:2560-6. http://www.ncbi.nlm.nih.gov/pubmed/8640706?dopt=AbstractPlus

154. Stadler WM, Kuzel T, Dumas M et al. Multicenter phase II trial of interleukin-2, interferon-alpha, and 13-cis-retinoic acid in patients with metastatic renal-cell carcinoma. J Clin Oncol. 1998; 16:1820-5. http://www.ncbi.nlm.nih.gov/pubmed/9586896?dopt=AbstractPlus

155. Parker MG, Atkins MB, Ucci AA et al. Rapidly progressive glomerulonephritis after immunotherapy for cancer. J Am Soc Nephrol. 1995; 5:1740-4. http://www.ncbi.nlm.nih.gov/pubmed/7787140?dopt=AbstractPlus

156. Koretz MJ, Lawson DH, York RM et al. Randomized study of interleukin 2 (IL-2) alone vs IL-2 plus lymphokine-activated killer cells for treatment of melanoma and renal cell cancer. Arch Surg. 1991; 126:898-903. http://www.ncbi.nlm.nih.gov/pubmed/1854252?dopt=AbstractPlus

157. Samuels BL, Hollis DR, Rosner GL et al. Modulation of vinblastine resistance in metastatic renal cell carcinoma with cyclosporine A or tamoxifen: a cancer and leukemia group B study. Clin Cancer Res. 1997; 3:1977-84. http://www.ncbi.nlm.nih.gov/pubmed/9815587?dopt=AbstractPlus

158. Fossa SD, Droz JP, Pavone-Macaluso MM et al. Vinblastine in metastatic renal cell carcinoma: EORTC phase II trial 30882. The EORTC Genitourinary Group. Eur J Cancer. 1992; 28A:878-80. http://www.ncbi.nlm.nih.gov/pubmed/1524914?dopt=AbstractPlus

159. Kish JA, Wolf M, Crawford ED et al. Evaluation of low dose continuous infusion 5-fluorouracil in patients with advanced and recurrent renal cell carcinoma. A Southwest Oncology Group Study. Cancer. 1994; 74:916-9. http://www.ncbi.nlm.nih.gov/pubmed/8039119?dopt=AbstractPlus

160. Tzannis ST, Hrushesky WJ, Wood PA et al. Irreversible inactivation of interleukin 2 in a pump-based delivery environment. Proc Natl Acad Sci USA. 1996; 93:5460-5. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=39268&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/8643597?dopt=AbstractPlus

161. Atzpodien J, Kirchner H, Illiger HJ et al. IL-2 in combination with IFN-alpha and 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial. Br J Cancer. 2001; 85:1130-6. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2375150&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/11710825?dopt=AbstractPlus

162. Halperin EC. Kidney cancer. Lancet. 1999; 353:594. http://www.ncbi.nlm.nih.gov/pubmed/10029013?dopt=AbstractPlus

163. Figlin RA, Thompson JA, Bukowski RM et al. Multicenter, randomized, phase III trial of CD8+ tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J Clin Oncol. 1999; 17:2521-9. http://www.ncbi.nlm.nih.gov/pubmed/10561318?dopt=AbstractPlus

164. Sawczuk IS, Graham Jr SD, Miesowicz F. Randomized, controlled trial of adjuvant therapy with ex vivo activated T cells (ALT) in T1-3a,b,c or T4N+,M0 renal cell carcinoma. Proc Am Soc Clin Oncol. 1997; 16:A1163.

165. Duran Garcia E, Santolaya R, Requena T. Treatment of malignant melanoma. Ann Pharmacother. 1999; 33:730-8. http://www.ncbi.nlm.nih.gov/pubmed/10410188?dopt=AbstractPlus

166. Cohen GL, Falkson CI. Current treatment options for malignant melanoma. Drugs. 1998; 55:791-9. http://www.ncbi.nlm.nih.gov/pubmed/9617594?dopt=AbstractPlus

167. Houghton A, Coit D, Bloomer W et al. NCCN melanoma practice guidelines. National Comprehensive Cancer Network. Oncology (Huntingt). 1998; 12:153-77.

168. Oncologic Drugs Advisory Committee Meeting. 55th meeting. Bethesda, MD: Food and Drug Administration; 1997 Dec 19.

169. Keilholz U, Conradt C, Legha SS et al. Results of interleukin-2-based treatment in advanced melanoma: a case record-based analysis of 631 patients. J Clin Oncol. 1998; 16:2921-9. http://www.ncbi.nlm.nih.gov/pubmed/9738559?dopt=AbstractPlus

170. Atkins MB, Lotze MT, Dutcher JP et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999; 17:2105-16. http://www.ncbi.nlm.nih.gov/pubmed/10561265?dopt=AbstractPlus

171. Dorval T, Negrier S, Chevreau C et al. Randomized trial of treatment with cisplatin and interleukin-2 either alone or in combination with interferon-alpha-2a in patients with metastatic melanoma: a Federation Nationale des Centres de Lutte Contre le Cancer Multicenter, parallel study. Cancer. 1999; 85:1060-6. http://www.ncbi.nlm.nih.gov/pubmed/10091789?dopt=AbstractPlus

172. Keilholz U, Goey SH, Punt CJ et al. Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: a randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group. J Clin Oncol. 1997; 15:2579-88. http://www.ncbi.nlm.nih.gov/pubmed/9215828?dopt=AbstractPlus

173. Marincola FM, White DE, Wise AP, Rosenberg SA Combination therapy with interferon alfa-2a and interleukin-2 for the treatment of metastatic cancer. J Clin Oncol. 1995; 13:1110-22. (IDIS 347746)

174. Rosenberg SA, Yang JC, Schwartzentruber DJ et al. Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b. J Clin Oncol. 1999; 17:968-75. http://www.ncbi.nlm.nih.gov/pubmed/10071291?dopt=AbstractPlus

175. Johnston SR, Constenla DO, Moore J et al. Randomized phase II trial of BCDT [carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen] with or without interferon alpha (IFN-alpha) and interleukin (IL-2) in patients with metastatic melanoma. Br J Cancer. 1998; 77:1280-6. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2150174&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/9579834?dopt=AbstractPlus

176. Legha SS, Ring S, Bedikian A et al. Treatment of metastatic melanoma with combined chemotherapy containing cisplatin, vinblastine and dacarbazine (CVD) and biotherapy using interleukin-2 and interferon-alpha. Ann Oncol. 1996; 7:827-35. http://www.ncbi.nlm.nih.gov/pubmed/8922197?dopt=AbstractPlus

177. Legha SS, Gianan MA, Plager C et al. Evaluation of interleukin-2 administered by continuous infusion in patients with metastatic melanoma. Cancer. 1996; 77:89-96. http://www.ncbi.nlm.nih.gov/pubmed/8630945?dopt=AbstractPlus

178. Rosenberg SA, Yang JC, White DE et al. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response. Ann Surg. 1998; 228:307-19. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1191483&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/9742914?dopt=AbstractPlus

179. Medical Research Council Renal Cancer Collaborators. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Lancet. 1999; 353:14-7. http://www.ncbi.nlm.nih.gov/pubmed/10023944?dopt=AbstractPlus

180. Pyrhonen S, Salminen E, Ruutu M et al. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol. 1999; 17:2859-67. http://www.ncbi.nlm.nih.gov/pubmed/10561363?dopt=AbstractPlus

181. Rosenberg SA, Yang JC, Schwartzentruber DJ et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med. 1998; 4:321-7. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2064864&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/9500606?dopt=AbstractPlus

182. Legha SS, Ring S, Eton O et al. Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma. J Clin Oncol. 1998; 16:1752-9. http://www.ncbi.nlm.nih.gov/pubmed/9586888?dopt=AbstractPlus

183. Atkins MB, Lee S, Flaherty LE et al. A prospective randomized phase III trial of concurrent biochemotherapy (BCT) with cisplatin, vinblastine, dacarbazine (CVD), IL-2 and interferon alpha-2b (IFN) versus CVD alone in patients with metastatic melanoma (E3695): An ECOG-coordinated intergroup trial. Proc ASCO. 2003; Abstract No. 2847.

184. Childhood acute myeloid leukemia/other myeloid malignancies. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2003 Jun 18.

185. Flanigan RC, Salmon SE, Blumenstein BA et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001; 345:1655-9. http://www.ncbi.nlm.nih.gov/pubmed/11759643?dopt=AbstractPlus

186. Tannock IF. Removing the primary tumor after the cancer has spread. N Engl J Med. 2001; 345:1699-700. http://www.ncbi.nlm.nih.gov/pubmed/11759650?dopt=AbstractPlus

187. Pantuck AJ, Belldegrun AS, Figlin RA. Nephrectomy and interleukin-2 for metastatic renal-cell carcinoma. N Engl J Med. 2001; 345:1711-2. http://www.ncbi.nlm.nih.gov/pubmed/11759660?dopt=AbstractPlus

188. Mickisch GH, Garin A, van Poppel H et al. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001; 358:966-70. http://www.ncbi.nlm.nih.gov/pubmed/11583750?dopt=AbstractPlus

189. Klotz L. Back to nephrectomy for patients with metastatic renal cancer. Lancet. 2001; 358:948-9. http://www.ncbi.nlm.nih.gov/pubmed/11583744?dopt=AbstractPlus

190. McDermott DF, Regan MM, Clark JI et al. Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol. 2005; 23:133-41. http://www.ncbi.nlm.nih.gov/pubmed/15625368?dopt=AbstractPlus

191. Eton O, Legha SS, Bedikian AY et al. Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial. J Clin Oncol. 2002; 20:2045-52. http://www.ncbi.nlm.nih.gov/pubmed/11956264?dopt=AbstractPlus

192. Keilholz U, Punt CJ, Gore M et al. Dacarbazine, cisplatin, and interferon-alfa-2b with or without interleukin-2 in metastatic melanoma: a randomized phase III trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol. 2005; 23:6747-55. http://www.ncbi.nlm.nih.gov/pubmed/16170182?dopt=AbstractPlus

193. Klapper JA, Downey SG, Smith FO et al. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma: a retrospective analysis of response and survival in patients treated in the Surgery Branch at the National Cancer Institute between 1986 and 2006. Cancer. 2008; 113:293-301. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3486432&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/18457330?dopt=AbstractPlus

194. Ives NJ, Stowe RL, Lorigan P et al. Chemotherapy compared with biochemotherapy for the treatment of metastatic melanoma: a meta-analysis of 18 trials involving 2,621 patients. J Clin Oncol. 2007; 25:5426-34. http://www.ncbi.nlm.nih.gov/pubmed/18048825?dopt=AbstractPlus

a. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:17-19.

b. AHFS drug information 2009. McEvoy GK, ed. Aldesleukin. Bethesda, MD: American Society of Health-System Pharmacists; 2009:915–24.

Medical Disclaimer