Info

🌱 來自: regimens of treatment of metastatic colorectal cancer

Irinotecan

• Topoisomerase I inhibitors

  • Inhibition of topoisomerase I → ↓ DNA unwinding → ↓ DNA replication and DNA degradation (because of ssDNA breaks)

• Dosing:

  • 180mg/BSA in mCRC
  • 125 mg/m2 × 4 wks w/ 2 wks rest. Homozygous for UGT1A1*28 allele & hepatic impairment (Tbili > ULN): ↓ dose, no specific adjustments suggested

• PK/PD: Extensive extravascular distribution, active drug (SN-38) hepatically glucuronidated via UGT1A1, renal excretion (25%), remainder eliminated via hepatic metabolism & biliary excretion, T1/2 6-12 h (irinotecan), 10-20 h (SN-38)

• AEs:

• detail: Adverse Reactions 󰒖

  • Diarrhea (DLT, early & delayed),
    • Cholinergic syndrome
  • Pulmonary toxicity (irinotecan)
  • myelosuppression (neutropenia),
  • abdominal pain,
  • N/V (mod. emetogenic potential),
  • alopecia,
  • fatigue,
  • ↑ LFTs & Tbili,
  • pulmonary tox (uncommon)

• DDI: CYP3A4 inducers/inhibitors (↓/↑ conc. of irinotecan)

• Clinical pearls:

  • Diarrhea <24 h: Acute cholinergic effect produced by inhibition of acetylcholinesterase by prodrug, treat w/ atropine.
  • Diarrhea >24 h: Mucosal cytotoxicity, treat w/ loperamide &/or octreotide.
  • Liposomal irinotecan (Onivyde) for tx of metastatic pancreatic CA in combination w/ 5-FU refractory to gemcitabine

---

• Note: FOLFIRI regimens may also be administered in combination with bevacizumab (Ref), cetuximab (Ref), panitumumab (Ref), ramucirumab (Ref), or ziv-aflibercept (Ref); refer to protocols for further information.
• IV: 180 mg/m2 over 90 minutes on days 1, 15, and 29 of a 6-week cycle (in combination with infusional leucovorin and bolus/infusion fluorouracil; leucovorin administered immediately following irinotecan; fluorouracil immediately following leucovorin); continue until disease progression or unacceptable toxicity.
• Adjusted dose level −1: 150 mg/m2.
• Adjusted dose level −2: 120 mg/m2.
• Further adjust if needed in decrements of ~20%.