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Irinotecan is a medication used to manage and treat a variety of solid tumors. It is in the DNA topoisomerase I inhibitor class of drugs. Also known as CPT-11, irinotecan is used adjunctively with other therapeutic agents against colorectal cancer as a first- or second-line treatment. This activity reviews the indications, action, and contraindications for irinotecan as a valuable agent in treating solid tumors such as colorectal, pancreatic, ovarian, and lung cancers. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for healthcare team members in the care of patients who receive treatment with this medication. Objectives: Identify the mechanism of action of irinotecan. Describe the adverse effects associated with irinotecan. Review the appropriate monitoring for Irinotecan. Explain the importance of collaboration and communication amongst the interprofessional team to ensure the optimal therapeutic results with irinotecan resulting in optimal patient outcomes. Access free multiple choice questions on this topic.

Life-threatening toxicities can occur even in patients who are in relatively good conditions. When a patient is unable to manage the side effect profile of irinotecan, it limits the therapeutic advantages that come with its use. Most of the irinotecan's side effect profile is due to its active metabolite, SN-38. Researchers have noted higher incidences of toxicity with genetic polymorphisms to the UDP-glucuronosyltransferase 1A1 gene. A particular polymorphism, UDP1A1*28, decreases the inactivation of SN-38, causing adverse toxic effects.[16] Patients with Gilbert disease, a syndrome of mildly decreased levels of UDP-glucuronyltransferase provoked at times of stress, suffer toxic side effects more commonly than patients not diagnosed with Gilbert disease.[5] Among the most common dose-limiting toxicities of irinotecan, commonly shared with the DNA topoisomerase I inhibitor group of chemotherapeutic agents, is diarrhea. Diarrhea is most widely noted within 7 to 10 days after treatment and can be life-threatening. High-dose loperamide, a dopamine agonist that does not cross the blood-brain barrier, is effective against diarrhea caused by irinotecan. It allows the ability to increase doses during chemotherapy to levels that patients can tolerate.[11]

The use of irinotecan for FDA-approved purposes such as colorectal and pancreatic carcinoma has greatly improved patient longevity. Factors that limit its usage mainly involve dose-limiting toxicities. Irinotecan's appropriate dosing regimen is still unclear, but the medical community has come to a consensus. The goal for the recommended dosing of irinotecan involves limiting side effects but still providing adequate treatment. The use of irinotecan requires the efforts of an interprofessional healthcare team to be maximally effective. To minimize its side effects, there have been attempts to manage drug-limiting diarrhea that can occur in patients. A combination of atropine with irinotecan or loperamide with irinotecan has demonstrated effectiveness in preventing diarrhea in some patients.[7][11] The medical community should continue to put in efforts to make irinotecan more tolerable during treatments. Irinotecan therapy requires the focused efforts of an interprofessional healthcare team. Board-certified oncologic pharmacists review dosing, check for interactions and assist with patient education, as well as consult with the oncologist or other ordering clinicians. Oncology nurses administer the medication, monitor for side effects, facilitate communication with the team, and chart their observations for use in making therapeutic decisions in the future. These are but two examples of interprofessional teamwork that can improve patient outcomes; this needs to be the norm in healthcare delivery. [Level 5] In a study completed at the Gustave Roussy Institute in 2002, the Department of Medicine conducted a study to determine the appropriate dosing of irinotecan in patients with cancer with hyperbilirubinemia. Researchers noted that the dose-limiting toxicities observed in the patients were mainly neutropenia and diarrhea. Patients with high bilirubin and alkaline phosphatase levels had a reduction in the clearance of irinotecan.[18] As healthcare professionals, it is essential to factor in a patient's hepatobiliary function. Since irinotecan and its metabolites are eliminated mainly through the liver, future treatments for patients should be adjusted to decrease accidental hyperbilirubinemia. [Level 5]

In a study completed at the Gustave Roussy Institute in 2002, the Department of Medicine conducted a study to determine the appropriate dosing of irinotecan in patients with cancer with hyperbilirubinemia. Researchers noted that the dose-limiting toxicities observed in the patients were mainly neutropenia and diarrhea. Patients with high bilirubin and alkaline phosphatase levels had a reduction in the clearance of irinotecan.[18] As healthcare professionals, it is essential to factor in a patient's hepatobiliary function. Since irinotecan and its metabolites are eliminated mainly through the liver, future treatments for patients should be adjusted to decrease accidental hyperbilirubinemia. [Level 5] Research has noted that irinotecan works better as a combination therapy. Two main combinations, XELIRI and FOLFIRI, are used to treat colorectal carcinoma. XELIRI is the combination of capecitabine with irinotecan, whereas FOLFIRI is the combination of 5-fluorouracil, leucovorin, and irinotecan. A meta-analysis in 2014 in China demonstrated that one was not superior to the other.[6] This data is useful for physicians and other healthcare providers in finding the most appropriate and best-suited chemotherapy regimen for their patients. Instead of choosing one over superiority, a healthcare provider can select by reasoning with patient status, tolerability, and age. [Level 5]