irinotecan; camptothecin (Camptosar, Topotecin, Onivyde, CPT-11)
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Introduction
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
- 125 mg/m2 IV over 90 minutes once weekly for 4 weeks
- 2 weeks hiatus
- reinitiate therapy with dose increased 25-50 mg/m2 as tolerated
- prophylactic loperamide 2-4 mg PO, repeated as needed with each loose bowel movement
- avoid extravasation
Injection: 20 mg/mL (5 mL), Onivyde: liposomal injection
Pharmacokinetics
- metabolized in liver
- 10% is eliminated in the urine
- 1/2life is of the parent drug is 6 hours
- active metabolite 1/2life is 10 hours
elimination via liver
elimination via kidney
1/2life = 6-10 hours
Monitor
complete blood count with each dose
Adverse effects
- common (> 10%)
- vasodilation
- insomnia
- dizziness
- fever (45%
- mild to moderate nausea (80%)/vomiting (12%)
- moderate to severe diarrhea
- myelosuppression: dose-limiting toxicity
- onset: 10 days
- nadir: 14-16 days
- recovery: 21-28 days
- neuromuscular & skeletal weakness (76%)
- dyspnea (22%)
- cough
- rhinitis
- diaphoresis
- less common (1-10%)
- other
- headache
- flu-like syndrome
- elevated liver function tests
- steatohepatitis (may effect mortality after hepatic resection for colorectal carcinoma metastases[4]
Drug interactions
- increased incidence of akathisia with prochlorperazine
- 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
More general terms
Component of
References
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Irinotecan Plus 5-FU Boosts Survival in Advanced Colon Cancer http://www.nci.nih.gov/clinicaltrials/results/irinotecan-plus0900
- ↑ 4.0 4.1 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: https://www.ncbi.nlm.nih.gov/pubmed/16648507
- ↑ 5.0 5.1 ARUP Consult: UGT1A1 Gene Analysis https://arupconsult.com/ati/ugt1a1-gene-analysis
- ↑ 6.0 6.1 Deprecated Reference
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60837
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60838
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3750
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=74990
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=357467
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=24360
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=72402