Irinotecan Liposome

See Mitotic Inhibitor Chemotherapy
Irinotecan Liposome is a pegylated formulation of the chemotherapeutic agent Irinotecan
1. Irinotecan is encapsulated by Polyethylene Glycol (PEG)-modified liposomes
2. Pegylated liposomal delivery of Irinotecan increases drug penetration into neoplasms and decreases drug clearance
  1. Increases the duration of Irinotecan exposure
  2. Lowers Irinotecan-associated systemic toxicity
Irinotecan is a semisynthetic derivative of camptothecin with antineoplastic activity
1. Camptothecin extracted from the Asian tree Camptotheca acuminata ("Happy Tree")
2. Camptothecin is a cytotoxic quinoline-based alkaloid
Irinotecan is a prodrug
1. Metabolized to SN-38 (7-ethyl-10-hydroxy-camptothecin) in vivo by carboxylesterase-converting enzyme
2. SN-38 is a thousand times more potent than Irinotecan in its inhibition of Topoisomerase 1
Irinotecan (and its active metabolite SN-38) is a Topoisomerase Inhibitor
1. SN-38 binds to topoisomerase 1, inhibiting DNA ligation
2. DNA breaks accumulate
3. Inhibits DNA Replication and transcription
4. Arrests cell cycle in S phase
5. Results in cell apoptosis and death

See other references for disease specific dosing protocols
Irinotecan Liposome 70 mg/m2 IV over 90 minutes every 2 weeks
1. Combined with other agents
2. Hold for Absolute Neutrophil Count <1500/mm3

Diarrhea (severe in 13% of patients)
1. Symptomatic management with fluid and Electrolyte replacement, Loperamide
2. Consider holding Diuretics
Interstitial Lung Disease
Hypersensitivity
Myelosuppression
1. Neutropenia higher risk with UGT1A1*28 Allele
2. Severe Neutropenia in 20% of patients
  1. Severe neutropenic Sepsis in up to 3% (and fatal in 0.8%) of patients on Irinotecan Liposome

Avoid in Lactation
Avoid in pregnancy (all trimesters)
1. Use reliable Contraception
Monitoring
1. Complete Blood Count
  1. Hold Irinotecan Liposome for Absolute Neutrophil Count <1500/mm3