Irinotecan

Definition

Irinotecan is a chemotherapeutic drug used in the treatment of various types of cancer, including colorectal, lung, and ovarian cancer. It works by inhibiting the enzyme topoisomerase I, which is essential for DNA replication and transcription, leading to cell death in rapidly dividing cancer cells.

5 Must Know Facts For Your Next Test

1. Irinotecan is a semi-synthetic derivative of the natural compound camptothecin, which was isolated from the bark of the Chinese tree Camptotheca acuminata.
2. Irinotecan is administered intravenously and is typically used in combination with other chemotherapeutic agents, such as 5-fluorouracil (5-FU) and leucovorin, to enhance its effectiveness.
3. The active metabolite of irinotecan, SN-38, is responsible for the drug's anticancer activity by inhibiting topoisomerase I and inducing DNA damage.
4. Irinotecan can cause severe side effects, including diarrhea, nausea, vomiting, and neutropenia (low white blood cell count), which require close monitoring and management.
5. Genetic variations in the enzyme UGT1A1, which is responsible for the metabolism of irinotecan, can affect the drug's pharmacokinetics and increase the risk of adverse effects.

Review Questions

• Explain the mechanism of action of irinotecan in the context of chemotherapeutic drugs.
  • Irinotecan is a chemotherapeutic agent that works by inhibiting the enzyme topoisomerase I, which is essential for DNA replication and transcription. By binding to topoisomerase I and preventing the enzyme from rejoining the broken DNA strands, irinotecan induces DNA damage and leads to cell death, particularly in rapidly dividing cancer cells. This mechanism of action makes irinotecan an effective chemotherapeutic drug for the treatment of various types of cancer, including colorectal, lung, and ovarian cancer.
• Describe the pharmacokinetic and pharmacodynamic considerations associated with the use of irinotecan in cancer treatment.
  • Irinotecan is administered intravenously and is typically used in combination with other chemotherapeutic agents to enhance its effectiveness. The active metabolite of irinotecan, SN-38, is responsible for the drug's anticancer activity by inhibiting topoisomerase I and inducing DNA damage. However, genetic variations in the enzyme UGT1A1, which is responsible for the metabolism of irinotecan, can affect the drug's pharmacokinetics and increase the risk of adverse effects, such as severe diarrhea, nausea, vomiting, and neutropenia. Therefore, close monitoring and management of these side effects are crucial when using irinotecan in cancer treatment.
• Evaluate the role of irinotecan in the context of combination chemotherapy regimens for the treatment of colorectal cancer.
  • Irinotecan is an important component of combination chemotherapy regimens for the treatment of colorectal cancer. By inhibiting topoisomerase I and inducing DNA damage in rapidly dividing cancer cells, irinotecan has demonstrated improved outcomes when used in combination with other chemotherapeutic agents, such as 5-fluorouracil (5-FU) and leucovorin. The synergistic effects of these combination regimens have led to increased response rates, prolonged progression-free survival, and improved overall survival in patients with colorectal cancer. However, the use of irinotecan in these regimens requires careful consideration of the potential for severe side effects, which necessitates close monitoring and management to ensure the best possible outcomes for patients.

Related terms

Topoisomerase I: An enzyme that catalyzes the breaking and rejoining of DNA strands, allowing for the unwinding of DNA during replication and transcription.

DNA Replication: The process of making a duplicate copy of a cell's DNA, which is essential for cell division and growth.

Apoptosis:

A form of programmed cell death that occurs in response to various stimuli, including DNA damage caused by chemotherapeutic agents like irinotecan.