Clinical management recommendations for HD IL-2 therapy

IssueConsiderationsManagement
Venous accessCentral line (for possible vasopressors)Typical
Double or triple lumenPICC line placement
Power inject and large volume capacityRemove temporary lines at end of cycle
Minimize catheter associated infectionVariations
Broviac/Hickman catheter
Subclavian/IJ catheter
IV fluidsMaintenance of volume with CLSTypical
Boluses for blood pressure supportD5NS or D5LR 10 ml - 125 ml/hr
Administration of drugsPRN KCL, HCO3, Mg replacement
Replacement of electrolytesVariations
IL-2 only compatible with D5WD5W, NS, 0.45% NaCl
InfectionsNo active infectionsTypical
PreventionGram + prophylactic antibiotic
IV catheter likeliest sourceVariations
Avoid unnecessary in-dwelling cathetersExpanded coverage per hospital
Chills/rigorsChills and rigors occur 1-2 hrs after IL-2Fever-Typical
Prophylaxis
FeverFever is common 2-4 hrs after IL-2Acetaminophen 650 mg 30 min pre-dose, q 4-6 hrs and prn
Indomethacin 25 mg q 6-8 hrs
Constitutional symptomsMuscle joint aches continuous and progressive during IL-2 treatmentFever-Variation
Naproxen
Ibuprofen
Chills-Typical
Meperidine 25 mg IV q 15 m prn
Morphine 2-4 mg IV q 15 m prn
Nausea/vomitingEpisodic occurrence throughout therapyTypical- Prophylaxis
Nausea > vomitingOndansetron 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 distressGastritis induced by stress, medicationsTypical
H2 blocker prophylaxis
Variation
PPI prophylaxis
Mucositis/stomatitisProgressive with continued treatmentTypical
No prophylaxis
Oncology mouthwash
DiarrheaCan be profuse and increases with therapyTypical
5HT-3 antagonist anti-emetic prophylaxisImodium
may have positively impactedLomotil
Narcotic
Break between IL-2 doses
Variations
5HT-3 antagonist prophylaxis
Patient monitoringI & O, WeightPer shift and daily
Blood pressure, pulse, respirations, tempQ 2-4 hrs
Blood workDaily
EKGContinuous cardiac monitoring
O2 SaturationQ 2-4 hrs
Mental status examinationQ 8 hrs
Increase frequency as needed
Aldesleukin/Interleukin-2 dose and administrationIL-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 D5WVariations: 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.
HypotensionMaintain systolic BP 80-90 mm hgFluid boluses, 250-500 ml NS
Blood pressure nadirs 4-6 hrs after each dose with diminished recovery with cumulative dosing2xday
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 nadirDC IL-2
Variations:
Dopamine 1-6 ug/kg/min
Progressive refractoriness to support measuresPressors with minimal fluids
Fluids without pressors
Cardiac arrhythmiasSinus tachycardiaManage 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 fibrillationMedical Conversion
Less commonCardizem as needed
Atrial fibrillationDigoxin
Ventricular tachycardiaMedical Conversion
Acute treatment
Discontinue IL-2
Renal functionTypical
OliguriaOutput less than 50-100 cc/8 hrs Fluid bolus, if no improvement next shift hold IL-2 dose
Rising creatinineCreatinine >3-4
Stop NSAIDS and nephrotoxic antiobiotics
Urine output and creatinine resolve after discontinuation of IL-2Hold overnight dose
If am creatinine improved continue
If only one kidney always consider obstruction of ureterVariations
Dopamine 1-6 mcg/kg/min
Furosemide
PulmonaryTachypnea/DyspneaTypical
Diagnose etiology and treatOxygen 2-4 L nasal cannula, increasing up to 35% rebreather
Hypoxic causes-Fluid overload, capillary leak, bronchospasmReassurance or sedative for anxiety, treat bronchospasm or acidosis if appropriate
Non hypoxic causesHold IL-2 dose if O2sat < 95%
Anxiety, fever, acidosis
Maintain O2sat > 92-5%Variation
Furosemide
Bronchodilators
Monitor bicarbonate
Peripheral edemaExpect to gain 5-10% body weightElevation, compression, limit fluid support in subsequent cycles
Treat edema symptomaticallyDiuretics upon conclusion of IL-2 dosing are not necessary but may speed process
Entrapment of peripheral nerves in upper extremity may need therapyTreat peripheral nerve pain
NeurotoxicityTypical
Protean manifestationsFormal neuro checks
Gradual onset with sudden worsening near end of cycleEnlist family evaluation
May persist after cessation of therapyLorazepam and Haloperidol
Delusions, Visual hallucinationsHold IL-2 liberally for suspected neurotoxicity
Warn patient of vivid dreams after discharge
DermatologicTypical
Rash, erythema, dry desquamationEmollient lotions and creams Oatmeal bath
PruritusAntihistamines
Moist dermatitisHold IL-2 dose
Variations
Crisco
Gabapentin
Naloxone
Narcotics
Nonalcohol, no steroid topicals
MetabolicHypomagnesemia, hypocalcemia (but low albumin - so corrected may be WNL), Hypokalemia-Daily electrolyte panels
Acidosis due to diarrhea, hypoperfusionCorrect electrolytes cautiously prn
Hypothyroidism a slow onset problemMagnesium 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 aminotransferasesResolves spontaneously
Stop acetaminophen if bilirubin > 5
Hematologic↓PlateletsTransfuse platelets if < 20 K
Lymphs ↓during IL-2, ↑post therapyOther abnormalities require no intervention
Eosinophils progressively ↑with several cyclesSignificant anemia needs evaluation for cause
EndocrineHypothyroidism - slow onset after completion of treatmentCheck TFTs at beginning of cycle and monitor TFTs with subsequent visits
Requires serial monitoring