Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 14.04.2021

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CAS number: 100286-90-6

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Irinotecan, like topotecan, is a semi-synthetic derivative of campothecin, an alkaloid extracted from fruits, leaves and the wood of Camptotheca acuminata . It is used as a cytostatic drug in chemotherapy. Irinotecan itself is a prodrug. It is converted into the active and more lipophilic active form mainly in the liver by a carboxyesterase by splitting off the carbamate group. Irinotecan inhibits the enzyme topoisomerase I(topoisomerase inhibitor).

Pharmacodynamics (Effect)
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Type I topoisomerases relax DNA, transforming superhelical DNA into relaxed DNA by reversibly cleaving one strand of duplex DNA. This creates the prerequisite for reading, i.e. transcription of the DNA. After successful DNA replication, the DNA gap is closed again. Type I topisomerases reversibly cleave only one strand of DNA at a time.

Topoisomerase inhibitors I allow DNA cleavage, stabilize the topoisomerase-DNA complex, and prevent the enzyme from closing the cleavage site again. Thus, DNA strand breakage remains to occur and the cell is driven into apoptosis. Topotecan as topoisomerase inhibitor I exerts the strongest antineoplastic activity in S phase (Brogden RN et al 1998).

Note: The type II topoisomerases act in an ATP-dependent manner. They are able to separate both DNA strands.

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Metastatic colorectal cancer

Primary treatment (first line): Irinotecan is used for first line treatment of metastatic colon cancer in combination with 5-fluorouracil (5-FU) and folinic acid.

Second line treatment: Irinotecan is used for second line treatment of metastatic colon cancer that has not responded or has responded inadequately to primary treatment with 5-FU and folinic acid.

Experimental data are available:

  • In adults: cervical carcinoma, esophageal carcinoma, gastric carcinoma, lung carcinomas, mesothelioma, pancreatic carcinoma, bile duct carcinoma.
  • In children and adolescents for: Ewing's sarcoma, neuroblastoma, rhabdomyosarcoma, PNET, Wilms' tumor as well as various brain tumors (ependymal tumor). Brain tumors (ependymoma, medulloblastoma, malignant glioma, glioblastoma, PNET).
  • Combination of cetuximab plus irinotecan in metastatic colorectal carcinoma (Horie Y et al. 2015).
  • Combination of docetaxel and irinotecan in metastatic melanoma (Tas F et al. 2003).
  • Combination of irinotecan and carboplatin in advanced non-small cell lung cancer (Takeda K et al. 2002).

Pregnancy/nursing period
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Irinotecan is contraindicated during lactation (see section 4.3). Although it is not known whether irinotecan passes into human breast milk, it is recommended to stop breastfeeding before starting therapy.

Fertility: No effects on male or female fertility have been observed in reproductive toxicology studies in rats. However, irinotecan, like other cytotoxic drugs, is genotoxic and effects on fertility, including male fertility, cannot be excluded.

Undesirable effects
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Irinotecan is characterised by severe diarrhoea (late diarrhoea), which only sets in after 5 days. These are treated with loperamide. In addition, irinotecan can trigger a "cholinergic syndrome" (inhibition of acetylcholinesterase) within 24 hours. This is characterised byflushing, diarrhoea, abdominal pain, sweating, miosis and increased tears and saliva flow (therapy with atropine).

Other possible adverse effects are myelosuppression (manifested in neutropenia, anemia and thrombopenia), alopecia, liver damage (elevation of transaminases, hyperbilirubinemia, jaundice to liver failure), Kidney damage (increase in creatinine, sometimes renal failure, especially with simultaneous fluid loss through diarrhoea), hypersensitivity (hypersensitivity, allergic reaction), colitis, ileus (inflammation and obstruction of the bowel).

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Last updated on: 14.04.2021