Irinotecan acts on topoisomerase to prevent religation of breaks in DNA. It may be given as a weekly intravenous injection for four out of six weeks or at a higher dose every three weeks.
Irinotecan may produce severe toxicity, with delayed onset diarrhoea requiring rehydration occurring in over 30% of patients. This can be ameliorated with the use of high-dose loperamide, 4 mg initially and 2 mg every two hours at the first sign of severe diarrhoea, continuing until the patient has been free of diarrhoea for 12 hours. If the diarrhoea does not settle, intravenous hydration should be considered and if neutropenia co-exists, start antibiotics active against Gram negative organisms. Less commonly an acute, early onset, cholinergic mediated diarrhoea may occur, but this settles with atropine. Other toxicities include neutropenia and alopecia. Patients who have had pelvic radiotherapy have been excluded from trials of irinotecan, because of concerns that this might cause more severe diarrhoea, so these patients should be treated with caution. Irinotecan is probably not a treatment which should be lightly instituted in frail and/or elderly patients.
Irinotecan is currently available on the PBS for patients with advanced and recurrent colorectal cancer who have failed therapy with fluoropyrimidines.5,6 There are data to suggest that the combination of irinotecan and 5-FU may be an optimal first-line therapy for patients with advanced colorectal cancer.7,8
As a second-line therapy, irinotecan treatment produces significantly improved survival compared to either best supportive care or infusional 5-FU. Approximately 20% of patients will have evidence of a major tumour response. When used first-line, two randomised studies have shown that the combination of irinotecan and 5-FU produces responses in approximately 50% of patients and provides a survival advantage of several months compared to patients treated with 5-FU and folinic acid. The median survival for patients with advanced colorectal cancer using combination therapy approaches 18 months.