Colorectal cancer: dilemmas regarding patient selection and toxicity prediction

Irinotecan (Campto, Rhône-Poulenc Rorer) is probably the most studied drug used as second-line treatment for colorectal cancer. Its main disadvantages are toxicity and cost. Delayed diarrhea and neutropenia are the most common toxic side effects, both of which can usually be predicted, by knowing the criteria for patients who are at increased risk for those side effects. These criteria include poor performance status (>2), bulky disease, previous abdominal-pelvic irradiation, hyperleukocytosis and increased bilirubin >1.5 x normal upper range. There are some other less common toxic effects of irinotecan, such as pneumonitis, cardiac arrhythmia, paralytic ileus, liver dysfunction, tumor lysis syndrome. While these side effects are very rare, physicians should be able to recognize them, because the number of patients being treated with irinotecan is increasing. The authors report four cases of probable irinotecan-related toxicity with fatal outcome in all 4 patients. Two of these 4 patients were not in the known risk categories for irinotecan toxicity. One patient died with signs of hepato-renal syndrome, the other with signs of rapid tumor lysis-like syndrome. Two other patients with bulky disease and performance status 2, had increased urea, creatinine and bilirubin serum levels after irinotecan administration, that could not be explained as manifestation of disease progression only. Data on all uncommon irinotecan toxic effects should be gathered and analyzed so that toxic effects, other than diarrhea and neutropenia, are better defined and predicted.