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Table 2 Clinical management recommendations for HD IL-2 therapy

From: High dose interleukin-2 (Aldesleukin) - expert consensus on best management practices-2014

Issue

Considerations

Management

Venous access

Central line (for possible vasopressors)

Typical

Double or triple lumen

PICC line placement

Power inject and large volume capacity

Remove temporary lines at end of cycle

Minimize catheter associated infection

Variations

Broviac/Hickman catheter

Subclavian/IJ catheter

IV fluids

Maintenance of volume with CLS

Typical

Boluses for blood pressure support

D5NS or D5LR 10 ml - 125 ml/hr

Administration of drugs

PRN KCL, HCO3, Mg replacement

Replacement of electrolytes

Variations

IL-2 only compatible with D5W

D5W, NS, 0.45% NaCl

Infections

No active infections

Typical

Prevention

Gram + prophylactic antibiotic

IV catheter likeliest source

Variations

Avoid unnecessary in-dwelling catheters

Expanded coverage per hospital

Chills/rigors

Chills and rigors occur 1-2 hrs after IL-2

Fever-Typical

Prophylaxis

Fever

Fever is common 2-4 hrs after IL-2

Acetaminophen 650 mg 30 min pre-dose, q 4-6 hrs and prn

Indomethacin 25 mg q 6-8 hrs

Constitutional symptoms

Muscle joint aches continuous and progressive during IL-2 treatment

Fever-Variation

Naproxen

Ibuprofen

Chills-Typical

Meperidine 25 mg IV q 15 m prn

Morphine 2-4 mg IV q 15 m prn

Nausea/vomiting

Episodic occurrence throughout therapy

Typical- Prophylaxis

Nausea > vomiting

Ondansetron 0.15 mg/kg q 8 hrs

Variations

Granisetron 1 mg daily

Ondansetron at longer interval

Compazine 10 mg po q 6 hrs

Use of antinausea agents prn

Epigastric distress

Gastritis induced by stress, medications

Typical

H2 blocker prophylaxis

Variation

PPI prophylaxis

Mucositis/stomatitis

Progressive with continued treatment

Typical

No prophylaxis

Oncology mouthwash

Diarrhea

Can be profuse and increases with therapy

Typical

5HT-3 antagonist anti-emetic prophylaxis

Imodium

may have positively impacted

Lomotil

 

Narcotic

 

Break between IL-2 doses

 

Variations

 

5HT-3 antagonist prophylaxis

Patient monitoring

I & O, Weight

Per shift and daily

Blood pressure, pulse, respirations, temp

Q 2-4 hrs

Blood work

Daily

EKG

Continuous cardiac monitoring

O2 Saturation

Q 2-4 hrs

Mental status examination

Q 8 hrs

Increase frequency as needed

Aldesleukin/Interleukin-2 dose and administration

IL-2 incompatible with salt solutions.

Typical: 600,000 IU/kg infused over 15 minutes Q 8 hrs up to 14 doses.

Dissolve in sterile water for injection Dilute into 50 cc D5W

Variations: 720,000 IU/kg Q 8 hrs Q 12 hrs < 14 maximum doses

Stop infusion, flush IV tubing with 50 cc D5W before and after each dose.

 

Hypotension

Maintain systolic BP 80-90 mm hg

Fluid boluses, 250-500 ml NS

Blood pressure nadirs 4-6 hrs after each dose with diminished recovery with cumulative dosing

2xday

Increase maintenance fluid rate

Phenylephrine 0.1-4.0 mcg/kg/min

Hold next dose

Prior to each dose anticipate ability to respond to next nadir

DC IL-2

Variations:

Dopamine 1-6 ug/kg/min

Progressive refractoriness to support measures

Pressors with minimal fluids

Fluids without pressors

Cardiac arrhythmias

Sinus tachycardia

Manage BP and fever

Common and progresses over a cycle

Peaks 2-4 hrs after dose with fever and hypotension

Must resolve prior to next dose

Supraventricular tachycardia, atrial fibrillation

Medical Conversion

Less common

Cardizem as needed

Atrial fibrillation

Digoxin

Ventricular tachycardia

Medical Conversion

Acute treatment

Discontinue IL-2

Renal function

 

Typical

Oliguria

Output less than 50-100 cc/8 hrs Fluid bolus, if no improvement next shift hold IL-2 dose

Rising creatinine

Creatinine >3-4

Stop NSAIDS and nephrotoxic antiobiotics

Urine output and creatinine resolve after discontinuation of IL-2

Hold overnight dose

If am creatinine improved continue

If only one kidney always consider obstruction of ureter

Variations

Dopamine 1-6 mcg/kg/min

Furosemide

Pulmonary

Tachypnea/Dyspnea

Typical

Diagnose etiology and treat

Oxygen 2-4 L nasal cannula, increasing up to 35% rebreather

Hypoxic causes-Fluid overload, capillary leak, bronchospasm

Reassurance or sedative for anxiety, treat bronchospasm or acidosis if appropriate

Non hypoxic causes

Hold IL-2 dose if O2sat < 95%

Anxiety, fever, acidosis

Maintain O 2 sat > 92-5%

Variation

Furosemide

Bronchodilators

Monitor bicarbonate

Peripheral edema

Expect to gain 5-10% body weight

Elevation, compression, limit fluid support in subsequent cycles

Treat edema symptomatically

Diuretics upon conclusion of IL-2 dosing are not necessary but may speed process

Entrapment of peripheral nerves in upper extremity may need therapy

Treat peripheral nerve pain

Neurotoxicity

 

Typical

Protean manifestations

Formal neuro checks

Gradual onset with sudden worsening near end of cycle

Enlist family evaluation

May persist after cessation of therapy

Lorazepam and Haloperidol

Delusions, Visual hallucinations

Hold IL-2 liberally for suspected neurotoxicity

Warn patient of vivid dreams after discharge

Dermatologic

 

Typical

Rash, erythema, dry desquamation

Emollient lotions and creams Oatmeal bath

Pruritus

Antihistamines

Moist dermatitis

Hold IL-2 dose

Variations

Crisco

Gabapentin

Naloxone

Narcotics

Nonalcohol, no steroid topicals

Metabolic

Hypomagnesemia, hypocalcemia (but low albumin - so corrected may be WNL), Hypokalemia-

Daily electrolyte panels

Acidosis due to diarrhea, hypoperfusion

Correct electrolytes cautiously prn

Hypothyroidism a slow onset problem

Magnesium and HCO3, particularly if diarrhea a problem

HCO3 < 18 meq/L hold dose of IL-2

Check TSH at beginning of cycle

RL as support fluids may decrease need for HCO3

Hepatic

↑Bilirubin (up to 10)

Monitor daily

↓Albumin (down to 1.8)

No intervention except if SGOT SGPT are >5x

↑Hepatic aminotransferases

Resolves spontaneously

 

Stop acetaminophen if bilirubin > 5

Hematologic

↓Platelets

Transfuse platelets if < 20 K

Lymphs ↓during IL-2, ↑post therapy

Other abnormalities require no intervention

Eosinophils progressively ↑with several cycles

Significant anemia needs evaluation for cause

Endocrine

Hypothyroidism - slow onset after completion of treatment

Check TFTs at beginning of cycle and monitor TFTs with subsequent visits

Requires serial monitoring