II. Indications

  1. Pancreatic Adenocarcinoma (metastatic)
    1. Combined with other agents

III. Contraindications

IV. Mechanism

  1. See Mitotic Inhibitor Chemotherapy
  2. 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
  3. 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
  4. 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
  5. 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

V. Medications

  1. Irinotecan Liposome injection solution: 43 mg per 10 ml vial

VI. Dosing

  1. See other references for disease specific dosing protocols
  2. 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

VII. Adverse Effects

  1. Diarrhea (severe in 13% of patients)
    1. Symptomatic management with fluid and Electrolyte replacement, Loperamide
    2. Consider holding Diuretics
  2. Interstitial Lung Disease
  3. Hypersensitivity
  4. 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

VIII. Safety

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

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