II. Indications
-
Pancreatic Adenocarcinoma (metastatic)
- Combined with other agents
III. Contraindications
- Bowel Obstruction
- Severe Hypersensitivity to Irinotecan or Irinotecan Liposome
- Interstitial Lung Disease
IV. Mechanism
- See Mitotic Inhibitor Chemotherapy
- Irinotecan Liposome is a pegylated formulation of the chemotherapeutic agent Irinotecan
- Irinotecan is encapsulated by Polyethylene Glycol (PEG)-modified liposomes
- Pegylated liposomal delivery of Irinotecan increases drug penetration into neoplasms and decreases drug clearance
- Increases the duration of Irinotecan exposure
- Lowers Irinotecan-associated systemic toxicity
-
Irinotecan is a semisynthetic derivative of camptothecin with antineoplastic activity
- Camptothecin extracted from the Asian tree Camptotheca acuminata ("Happy Tree")
- Camptothecin is a cytotoxic quinoline-based alkaloid
-
Irinotecan is a prodrug
- Metabolized to SN-38 (7-ethyl-10-hydroxy-camptothecin) in vivo by carboxylesterase-converting enzyme
- 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
- SN-38 binds to topoisomerase 1, inhibiting DNA ligation
- DNA breaks accumulate
- Inhibits DNA Replication and transcription
- Arrests Cell Cycle in S phase
- Results in cell apoptosis and death
V. Medications
- Irinotecan Liposome injection solution: 43 mg per 10 ml vial
VI. Dosing
- See other references for disease specific dosing protocols
- Irinotecan Liposome 70 mg/m2 IV over 90 minutes every 2 weeks
- Combined with other agents
- Hold for Absolute Neutrophil Count <1500/mm3
VII. Adverse Effects
-
Diarrhea (severe in 13% of patients)
- Symptomatic management with fluid and Electrolyte replacement, Loperamide
- Consider holding Diuretics
- Interstitial Lung Disease
- Hypersensitivity
- Myelosuppression
- Neutropenia higher risk with UGT1A1*28 Allele
- Severe Neutropenia in 20% of patients
- Severe neutropenic Sepsis in up to 3% (and fatal in 0.8%) of patients on Irinotecan Liposome
VIII. Safety
- Avoid in Lactation
- Avoid in pregnancy (all trimesters)
- Use reliable Contraception
- Monitoring
- Complete Blood Count
- Hold Irinotecan Liposome for Absolute Neutrophil Count <1500/mm3
- Complete Blood Count
IX. Resources
- Irinotecan Liposome (DailyMed)