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irinotecan; camptothecin (Camptosar, Topotecin, Onivyde, CPT-11)

Tradename: Camptosar Indications: - metastatic colorectal adenocarcinoma failure of 5-fluorouracil treatment - anaplastic astrocytoma [6] - glioblastoma multiforme - non small cell carcinoma - small cell carcinoma - Ewing sarcoma - pancreatic cancer (Onivyde) in combination with 5-fluorouracil & leucovorin after progression on gemcitabine-based therapy Dosage: 1) 125 mg/m2 IV over 90 minutes once weekly for 4 weeks 2) 2 weeks hiatus 3) reinitiate therapy with dose increased 25-50 mg/m2 as tolerated 4) prophylactic loperamide 2-4 mg PO, repeated as needed with each loose bowel movement 5) avoid extravasation Injection: 20 mg/mL (5 mL), Onivyde: liposomal injection Pharmacokinetics: 1) metabolized in liver 2) 10% is eliminated in the urine 3) 1/2life is of the parent drug is 6 hours 4) active metabolite 1/2life is 10 hours Monitor: complete blood count with each dose Adverse effects: 1) common (> 10%) - vasodilation - insomnia - dizziness - fever (45% - mild to moderate nausea (80%)/vomiting (12%) - moderate to severe diarrhea - early diarrhea (50%) - < 24 hours after treatment - responds to atropine - late diarrhea (88%) - > 24 hours after treatment - mean onset 11 days after treatment - mean duration: 3-7 days - myelosuppression: dose-limiting toxicity - onset: 10 days - nadir: 14-16 days - recovery: 21-28 days - neuromuscular & skeletal weakness (76%) - dyspnea (22%) - cough - rhinitis - diaphoresis 2) less common (1-10%) - thrombophlebitis 3) other - headache - flu-like syndrome - elevated liver function tests - steatohepatitis (may effect mortality after hepatic resection for colorectal carcinoma metastases [4] Drug interactions: 1) increased incidence of akathisia with prochlorperazine 2) diuretics (fluid & electrolyte balances due to diarrhea) Laboratory: - UGT1A1 genotyping - see ARUP consult [5] Mechanism of action: - inhibitor of topoisomerase 1 - down-regulation of PRMT7 confers increased sensitivity of Top1 to irinotecan

Related

UGT1A1 genotyping

General

alkaloid topoisomerase-1 inhibitor

Properties

MISC-INFO: elimination route LIVER KIDNEY 1/2life 6-10 HOURS

Database Correlations

PUBCHEM correlations

References

  1. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Irinotecan Plus 5-FU Boosts Survival in Advanced Colon Cancer http://www.nci.nih.gov/clinicaltrials/results/irinotecan-plus0900
  4. Vauthey JN et al, Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 2006, 24:2065 PMID: 16648507
  5. ARUP Consult: UGT1A1 Gene Analysis https://arupconsult.com/ati/ugt1a1-gene-analysis
  6. Deprecated Reference

Component-of

5-fluorouracil/irinotecan/leucovorin/oxaliplatin (FOLFIRINOX)