Key Terms: Alkaloid, Anorexia, Apoptosis, Diuretic, Inflammation.
Definition
Irinotecan is a drug used to treat certain types of cancer. Irinotecan, also known as CPT-11, is available under the trade name Camptosar, and may also be referred to as irinotecan hydrochloride or camptothecin-11.
Purpose
Irinotecan is an antineoplastic agent used to treat cancer. A primary use of the drug is treatment of colon or rectal cancers that have recurred or progressed while the patient was on 5-FU (fluorouracil) therapy. Irinotecan also can be given as first line therapy with 5-FU and leucovorin for patients with metastatic colon or rectal cancer. Other uses for irinotecan include treatment of small cell lung cancer, nonsmall cell lung cancer, ovarian cancer, stomach cancer, breast cancer, pancreatic cancer, leukemia, lymphoma, and cervical cancer.
Several 2003 studies showed some potential new uses for irinotecan. One reported that a combination of irinotecan and docetaxel can help patients with esophageal cancer who have been extensively pretreated with cisplatin. Weekly use of irinotecan has shown preliminary results in treating patients with nonsmall cell lung cancer with minimal side effects. Another 2003 study reported that when used in combination with cancer drugs cisplatin and epirubicin, irinotecan might have promising broad antitumor activity. In the future, irinotecan might be used in combination therapies to treat many types of tumors.
Description
Irinotecan is a synthetic derivative of the naturally occurring compound camptothecin. Camptothecin belongs to a group of chemicals called alkaloids and is extracted from plants such as camptotheca acuminata. Captothecin was initially investigated as a chemotherapeutic agent due to its anticancer activity in laboratory studies. The chemical structure and biological action of irinotecan is similar to that of camptothecin and topotecan.
Irinotecan inhibits the normal functioning of the enzyme topoisomerase I. The normal role of topoisomerase I is to aid in the replication, recombination, and repair of deoxyribonucleic acid (DNA). Higher levels of topoisomerase I have been found in certain cancer tumors compared to healthy tissue. Inhibiting topoisomerase I causes DNA damage. This damage leads to apoptosis, or programmed cell death.
Recommended Dosage
Patients should be carefully monitored during irinotecan treatment for toxicity. Irinotecan is given at a dose of 125 mg per square meter of body surface area per week for four weeks, followed by a two week rest period. Other dosing schedules include 100 mg per square meter of body surface area per day for three days every three weeks, or 100-115 mg per square meter of body surface area per week, or 200-350 mg per square meter of body surface area every 3 weeks. The drug is administered through the vein over a 90-minute period. The initial dose of irinotecan may be adjusted downward depending on patient tolerance to the toxic side effects of irinotecan.
Treatment may be continued as long as intolerable side effects do not develop and patients continue to benefit from the treatment.
Precautions
Irinotecan should only be used under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Special caution, especially in those 65 years and older, should be taken to monitor the toxic effects of irinotecan, particularly diarrhea, nausea, and vomiting. Because irinotecan is administered intravenously, the site of infusion should be monitored for signs of inflammation. Should inflammation occur, flushing the site with sterile water and applying ice are recommended. Irinotecan may cause nausea and vomiting, and premedication with antiemetic agents is recommended.
Neither the effects of irinotecan in patients with significant liver dysfunction nor the safety of irinotecan in children have been established. Irinotecan should not be administered to pregnant women. Women of child-bearing age are advised not to become pregnant during treatment with this drug.
Side Effects
Early- or late-onset diarrhea are common side effects of irinotecan. Late-onset diarrhea, occurring more than 24 hours after irinotecan administration, can be life-threatening and should be treated promptly. Patients should immediately report diarrhea to their physician. Patients can also take the antidiarrheal drug loperamide as prescribed by their physician at the first sign of diarrhea. Suppression of bone marrow function is another serious side effect commonly observed in this treatment. Additional side effects, including nausea, vomiting, anorexia (loss of appetite), pain, fatigue, and hair loss (alopecia) may occur.
Interactions
Irradiation treatment during the course of irinotecan treatment is not recommended. Patients who have received prior pelvic or abdominal irradiation treatment should notify their physician. Since irinotecan may cause diarrhea, the use of laxatives should be avoided. The use of diuretics should be closely monitored. The adverse side effects caused by irinotecan may be increased by other antineoplastic agents having similar adverse effects and should generally be avoided.
Resources
Periodicals
"Cisplatin, Irinotecan, and Epirubicin Have Promising Broad Antitumor Activity." Cancer Weekly October 14, 2003:12.
"Irinotecan and Docetaxel Shows Some Activity in Extensively Pretreated Patients." Clinical Trials Week October 13, 2003: 25.
"Weekly Irinotecan Showed Antitumoral Activity and Minimum Toxicity in NSCCLC." Clinical Trials Week October 13, 2003: 25.
—Marc Scanio; Teresa G. Odle
