Irinotecan

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Information about Irinotecan

  Irinotecan and topotecan are semisynthetic derivatives of the plant alkaloid camptothecin and are used as antineoplastic agents in the therapy of colorectal, ovarian and non-small cell lung cancer. 

Liver safety of Irinotecan

Both irinotecan and topotecan are associated with an appreciable rate of serum enzyme elevations during therapy, and irinotecan has been implicated in causing steatohepatitis when given as cyclic anticancer therapy. 

Mechanism of action of Irinotecan

Irinotecan (eye" ri noe tee' kan) and topotecan (toe" poe tee' kan) are semisynthetic derivatives of camptothecin, a plant alkaloid derived from the Chinese tree, Camptotheca acuminata.  Both drugs appear to act by blocking DNA topoisomerase I, which is responsible for relaxation of supercoiled double stranded DNA so that replication can proceed.  Topoisomerase I activity is particularly increased in cancer cells.  Irinotecan and topotecan have antineoplastic activity against colorectal, non-small cell lung and breast cancer in vivo and in vitro. 

FDA approval information for Irinotecan

Irinotecan and topotecan were both approved for use in the United States in 1996 and continue to be used in oncology practice.  Current formal indications for irinotecan are advanced colorectal cancer alone or in combination with other antineoplastic agents (usually fluorouracil). 

Dosage and administration for Irinotecan

Irinotecan is available generically and under the brand name Camptosar in 2, 5 and 15 mL vials of 20 mg/mL.  The typical dose varies is based upon body weight and is adjusted by whether it is used alone or in combination with other anticancer agents.  The approved indications for topotecan include advanced or metastatic ovarian and cervical cancer and small cell lung cancer (after failure of first line chemotherapy).  Topotecan is available in solution in 4 mg single dose vials generically and under the trade name Hycamtin.  The typical dose varies by indication and body weight. 

Side effects of Irinotecan

Side effects of irinotecan and topotecan are similar and include bone marrow suppression, nausea, vomiting, abdominal pain, stomatitis, diarrhea, fatigue, hair loss and peripheral neuropathy.  Infusions of irinotecan can be associated with severe diarrhea which is typically delayed and is treated with loperamide.  Irinotecan also can cause an acute cholinergic syndrome marked by hypotension, diarrhea, sweating, lacrimation and fatigue, which is typically treated with atropine. 


Antineoplastic Agents

Alkylating Agents - Altretamine, Bendamustine, Busulfan, Carmustine, Chlorambucil, Cyclophosphamide, Dacarbazine, Ifosfamide, Lomustine, Mechlorethamine, Melphalan, Procarbazine, Streptozocin, Temozolomide, Thiotepa, Trabectedin

Platinum Coordination Complexes - Carboplatin, Cisplatin, Oxaliplatin

Antibiotics Cytotoxic - Bleomycin, Dactinomycin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitomycin, Mitoxantrone, Plicamycin, Mithramycin, Valrubicin

Antimetabolites Antifolates - Methotrexate, Pemetrexed, Pralatrexate, Trimetrexate

Purine Analogues - Azathioprine, Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Nelarabine, Pentostatin, Thioguanine

Pyrimidine Analogues - Azacitidine, Capecitabine, Cytarabine, Decitabine, Floxuridine, Fluorouracil, Gemcitabine, Trifluridine/Tipracil

Biologic Response Modifiers - Aldesleukin (IL-2), Denileukin Diftitox, Interferon gamma

Histone Deacetylase Inhibitors - Belinostat, Panobinostat, Romidepsin, Vorinostat

Hormonal Agents Antiandrogens - Abiraterone, Bicalutamide, Cyproterone, Enzalutamide, Flutamide, Nilutamide

Antiestrogens (including Aromatase Inhibitors) - Anastrozole, Exemestane, Fulvestrant, Letrozole

Selective Estrogen Receptor Modulators - Raloxifene, Tamoxifen, Toremifene

Gonadotropin Releasing Hormone Analogues - Degarelix, Goserelin, Histrelin, Leuprolide, Triptorelin

Peptide Hormones - Lanreotide, Octreotide, Pasireotide

Monoclonal Antibodies - Alemtuzumab, Atezolizumab, Avelumab, Bevacizumab, Blinatumomab, Brentuximab, Cetuximab, Daratumumab, Dinutuximab, Durvalumab, Elotuzumab, Gemtuzumab, Inotuzumab Ozogamicin, Ipilimumab, Necitumumab, Nivolumab, Ofatumumab, Olaratumab, Panitumumab, Pembrolizumab, Pertuzumab, Ramucirumab, Rituximab, Tositumomab, Trastuzumab

Protein Kinase Inhibitors - Abemaciclib, Acalabrutinib, Afatinib, Alectinib, Axitinib, Bortezomib, Bosutinib, Brigatinib, Cabozantinib, Carfilzomib, Ceritinib, Cobimetinib, Copanlisib, Crizotinib, Dabrafenib, Dasatinib, Enasidenib, Erlotinib, Gefitinib, Ibrutinib, Idelalisib, Imatinib, Ivosidenib, Ixazomib, Lapatinib, Lenvatinib, Neratinib, Nilotinib, Niraparib, Olaparib, Osimertinib, Palbociclib, Pazopanib, Ponatinib, Regorafenib, Ribociclib, Rucaparib, Ruxolitinib, Sonidegib, Sorafenib, Sunitinib, Trametinib, Vandetanib, Vemurafenib, Vismodegib

Taxanes - Cabazitaxel, Docetaxel, Paclitaxel

Topoisomerase Inhibitors - Etoposide, Irinotecan, Teniposide, Topotecan

Tyrosine Kinase Receptor Inhibitors See Protein Kinase Inhibitors

Vinca Alkaloids - Vinblastine, Vincristine, Vinorelbine

Miscellaneous - Asparaginase (Pegaspargase), Bexarotene, Eribulin, Everolimus, Hydroxyurea, Ixabepilone, Lenalidomide, Mitotane, Omacetaxine, Pomalidomide, Temsirolimus, Thalidomide, Venetoclax

 

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