Irinotecan side effects

Irinotecan (CPT-11) is approved for colorectal tumors. It is given by intravenous infusion. The most severe side effect is diarrhea, which can be severe and needs to be treated by a physician. Temporary liver dysfunction is generally asymptomatic. The other side effects are the same as those produced by topotecan. 

Patients should be closely monitored for side effects that require aggressive intervention such as irinotecan-induced diarrhea and bevacizumab-induced GI perforation. Patients should be evaluated for other treatment-specific side effects such as oxaliplatin-induced neuropathy, cetuximab and panitumumab-induced skin rash, and bevacizumab-induced hypertension and proteinuria. 

Hardman, W. E., Moyer, M. P., and Cameron, I. L., 1999, Fish oil supplementation enhanced CPT-11 (irinotecan) efficacy against MCF7 breast carcinoma xenografts and amehorated intestinal side-effects, Br. J. Cancer SI 440-448. 

Irinotecan treatment schedules differ from 125 to 150 mg/m2 once a week for 4 wk followed by a 2-wk drug free interval (United States), to 350 mg/m2 once every 3 wk (Europe), or 100 mg/m2/wk or 150 mg/m2 every 2 wk (Japan). Differing intermittent treatment schedules using cytokine support for neutropenia, or intensive loperamide to counteract diarrhea, have also been reported (14). These tolerable CPT-11 regimens have produced median durations of response that range from 5.6 to 10.6 mo in colorectal patients disease stabilization occurs in 30 to 71 % (40). Response rates of 26% and 32% have been reported for previously untreated colorectal cancer patients higher response rates have been reported for non-5-FU-refractory patients (only 7-21%). Symptoms of diarrhea, nausea, and vomiting are common toxicities other side effects are asthenia, abdominal pain, leukopenia, and neutropenia. In the US trials at least one of these adverse... 

SN-38, the major active metabolite of irinotecan formed from hepatic carboxylesterase, accounts for both the cytotoxic activity and the gastrointestinal side-effects. The metabolism of SN-38 is catalysed via CYP3A4 to a much less active metabolite - aminopentane carboxylic acid,... 

Topotecan is associated with bone marrow suppression (dose-limiting neutropenia). Other side effects include mild to moderate nausea/vomiting, alopecia, and abdominal complaints. Irinotecan has been associated with both acute (within 24 hours) and delayed (3 to 11 days posttherapy) diarrhea. The diarrhea may be severe or prolonged and may lead to fluid and electrolyte imbalances. The early diarrhea may be mediated by cholinergic mechanisms and can sometimes be ameliorated by administration of atropine. 

The camptothecins were discovered in extracts from the Chinese tree Camptotheca acuminata. Initial studies showed that camptothecins had antitumor activity, but clinical trials demonstrated severe side effects and toxicity. Numerous camptothecin analogues have been synthesized several have received FDA approval (irinotecan and topotecan), whereas others are still in clinical trials. 

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