Systemic Therapy Program

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Drug Monographs
Treatment Regimens

Scientific Name:
ALDESLEUKIN
Brand Name(s):
Proleukin®

Drug Monograph

Pharmacology

Mechanism of Action

Promotes proliferation, differentiation, and recruitment of T and B cells, natural killer (NK) cells, and thymocytes. It also causes cytolytic activity in some lymphocytes and subsequent interactions between lymphokine-activated killer (LAK) cells and tumour infiltrating lymphocytes (TIL). It causes multiple immunological effects including activation of cellular immunity with lymphocytosis, eosinophilia, and thrombocytopenia; production of cytokines (including tumour necrosis factor, interleukin-1, and g-interferon); and inhibition of tumour growth.

Pharmacokinetics

Oral Absorption: not absorbed orally
Distribution: 2 compartment model: 30% distributed to plasma initially; 90% rapid uptake into the liver, kidneys & lungs; enters breast milk
Cross blood brain barrier?  No information
Vd:  4-7L  
PPB:  no information
Metabolism:  Renal; >80% metabolized in kidneys to amino acids
Excretion: Renal:  urine- yes
t½a- 6-13 minutes  t½b- 85-120 minutes  Cl- 268mL/min

Side Effects

NOTE: Adverse Effects with intralesional injections are usually mild or none
Adverse effects with systemic administration are listed below:
IMMEDIATE ONSET
(hours to days)
capillary-leak syndrome (hypotension, reduced organ perfusion)
*  flu-like syndrome (fever, chills, rigors) 52%
pulmonary edema
EARLY ONSET
(days to weeks)
*  cardiovascular effects (hypotension, arrythmias, myocardial ischemia or infarction, myocarditits, angina, tachycardia-23%)
   respiratory effects (dyspnea, lung disorders) 43%
   nervous system effects (change inmental status, speech difficulties, hallucinations), somnolence 22%
   renal dysfunction with oliguria- 63% or anemia- 20%
   gastrointestinal effects- diarrhea 67%, vomiting 50%
   hepatic and biliary effects- increased bili (40%) and AST (23%)
   dermatologic effects- rash (42%), pruritis (24%)
   sensitivity to sunlight

Therapeutics

Approved Indications

• Renal cell carcinoma
• Metastatic malignant melanoma
• In-Transit malignant melanoma

Routes

SC
IV
Intralesional

Administration

• May be given as intralesional injection(s) into topical melanoma lesion(s) by qualified physician
• Subcutaneous self-administration (or administered by home caregiver)
• Mix in 50mL bag of 5% Dextrose; Infuse over 15 minutes

IV Compatibility

Sterile water, 5% dextrose- NO bacteriostatic water!

Dosing

Intralesional Administration:
• Local injection into tumor site- dosing at the discretion of the qualified surgeon or physician
• Doses range from 0.3 MIU to 6 MIU, depending on lesion size
Initial treatment:
• 600,000 IU/Kg IV q8h for up to 14 doses, 9 day rest then repeat up to 14 more doses
• Usually only 18-20 of full 28 doses given (full dose not tolerated)
Retreatment:
• After 4 weeks from last dose, repeat initial treatment schedule

Antiemetic Risk

NO RISK for Intralesional Injections
HIGH RISK (30-90% of patients) for Systemic Administration
• Use a serotonin receptor antagonist PLUS dexamethasone pre-chemotherapy and post-chemotherapy

Contraindications

• Uncontrolled or treatment-resistant arrythmias • Recurrent chest pain and ECG abnormalities (angina, myocardial infarction) • Impaired cardiac function • Organ allografts • Impaired pulmonary functions

Monitoring

Clinical Monitoring

RECOMMENDED CRITERIA
• Baseline and regular renal function tests [serum creatinine, electrolytes & BUN]
• Regular assessment of pulmonary and cardiac function, including auscultation and x-rays*
• Routine toxicity ratings for Flu-Like Symptoms and Cortical Toxicity*
FLU-LIKE SYMPTOMS
(Arthralgia, myalgia, diaphoresis, rigours/chills)
0. None
1. Mild
2. Moderate
3. Severe
Rated at Each Clinic Visit
SUGGESTED CRITERIA
• Cortical toxicity ratings if there is evidence of somnolence or central nervous system toxicity*
CORTICAL
0. None
1. Mild somnolence
2. Moderate somnolence
3. Severe somnolence, confusion, hallucination
4. Coma, seizures

* Monitoring only for systemic administration

Extravasation Hazard

IRRITANT: injection site reactions- nodules or indurations at injection site Management- cold compresses; moist heat or warm packs Follow Extravasation Guidelines DO NOT manage extravasations when given intrelesionally

Significant Interactions

Myelosuppressive agents, radiotherapy, cardiotoxic medications (including anthracyclines), CNS depressants, contrast media, cyclophosphamide, dacarbazine, glucocorticosteroids, opioids, hepatotoxic medications, nephrotoxic medications, hypotension-producing medications.

Product Information

Commercial Product Description

Single use vials of 22 million IU, for reconstitution with 1.2mL Sterile Water for Injection- Keep refrigerated.

Pharmaceutical Considerations

Injection:
• Single-use vials containing 22 MU aldesleukin (1.3mg) with mannitol 50mg/mL, sodium dodecyl sulphate 0.18mg/mL (and buffers 0.17mg monobasic sodium phosphate and 0.89mg dibasic sodium phosphate) when reconstituted with 1.2mL Sterile Water for Injection.  Preservative-free
Preparation:
• Reconstitute with 1.2mL Sterile Water for Injection to a final concentration of 18MU/mL (or 1.1mg/mL).
• Add SWFI to side of vial when reconstituting, and gently swirl vial to dissolve powder.
• Do not shake vial to prevent foaming of final solution. 
• Reconstituted vials may be dispensed to qualified surgeon or physician for intralesional injections.
Reconstituted Solution for Injection:
• Clear colourless to slightly yellow liquid. 
• Store in refrigerator at 2-8oC for up to 48 hours; do not freeze. 
• Solution may be brought to room temperature before administration to patient.
Diluted Solution for Infusion:
• Dilute measured dose in 50mL of 5% Dextrose solution for infusion over 15 minutes. 
• If the dose of aldesleukin is below 1.5mg (e.g. patients <40Kg), dilute in a smaller volume of D5W (to remain within concentration range of 30-70µg/mL). 
• Solutions outside the concentration range should not be used.  In-line filters should not be used during infusion of aldesleukin.  Administer within 48 hours of reconstitution.
• Incompatible with Bacteriostatic Water for Injection- will form aggregates. 
• Manufacturer recommends that aldesleukin should not be administered with other drugs in the same container.

Handling Risk Level

Pregnancy CPOSSIBLE HAZARDOUS DRUG
FDA Pregnancy Risk Factor C

  • Consider handling this drug using precuations outlined in CCNS Policies for Occupational Safety, Preparing Cancer Chemotherapy and Administering Cancer Chemotherapy

Note

GUIDELINES:
In-Transit Metastatic Melanoma
pCODR Recommendation:  Unresectable in-transit metastatic melanoma (i.e., patients with rapidly developing in-transit metastases after surgery or patients who present with multiple in-transit metastases unsuitable for surgical resection). Funding should be for aldesleukin when administered as an intralesional injection. June 22, 2015

Visit the Pan-Canadian Oncology Drug Review website (www.pcodr.ca) for the guidelines on aldes;eukin for metastatic melanoma.
• Go to "Additional Information" tab (above) for links to pCODR Reviews

Availability & Funding

Administrative Information (Nova Scotia)

CCNS Provincial Formulary Status- Specialty Level- • For Intralesional Injections by Qualified Surgeon or Physican • For high-dose Systemic Therapy Community Level for Low Dose Systemic Therapy • Take Home Prescription- Restricted Use • Go to "Additional Information" tab (above) for links to Provincial Formulary of Cancer Drugs Pharmacare Formulary Status: Non-Formulary NOTE: It is recommended to limit ordering of this medication to standard preprinted order forms, for patient safety

New Cancer Drug Fund Status (Nova Scotia)

New Cancer Drug Fund (NCDF) funding approved for: As a single agent for intralesional injection for patients with unresectable in-transit metastatic melanoma (ie patients with rapidly developing in-transit metastases after surgey or patients who present with multiple in-transit metastases unsuitable for surgical resection).



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