CPT-11 (
irinotecan) is a promising
anticancer agent with a novel mechanism of action dependent on the inhibition of the
DNA eukaryotic
enzyme,
topoisomerase I. The clinical utility of
CPT-11 in advanced
colorectal cancer has been documented in more than 400 patients recruited in phase II clinical trials in Europe, Japan, and United States. Among 178 eligible patients in a multicenter European study, the overall response rate to
CPT-11 on a once-every-3-weeks regimen was 18%, and the median duration of response was 9.1 months. Thirty-two percent of the patients had no evidence of
disease progression at 6 months. These results were similar in
chemotherapy-naive and pretreated patients. These findings are consistent with the results of other studies conducted in Japan and the United States in which a weekly
CPT-11 regimen was associated with response rates of 15% to 32% in
chemotherapy-naive or pretreated patients. The principal adverse events of
CPT-11 are
neutropenia and delayed
diarrhea, which in the European studies developed as grade 3 or 4 toxicity in 21% and 12% of the cycles (47% and 38% of patients), respectively.
Neutropenia did not appear to be cumulative, with total recovery by day 22 in most cases.
Loperamide was considered the most effective agent for controlling delayed
diarrhea. Other adverse events included an early
cholinergic-like syndrome (consisting of diaphoresis, early
diarrhea, and
abdominal cramps),
nausea and
vomiting,
fatigue, and
alopecia. In conclusion,
CPT-11 has shown promising antitumor activity in the treatment of patients with advanced
colorectal cancer, including those refractory to
5-fluorouracil (5-FU)-based regimens, suggesting no cross-resistance to
5-FU.
CPT-11 appears to have activity similar to that of
5-FU in first-line treatment and, moreover, remains active after failure of
5-FU therapy. The specific gastrointestinal toxicity is manageable, and a better control of this type of toxicity is expected in the future.
CPT-11 would therefore appear a welcome addition to the oncology armamentarium for this difficult-to-treat
malignancy.