Two trials of irinotecan in colorectal cancer suspended on safety concerns

Two US clinical trials of the topoisomerase I inhibitor irinotecan,which is marketed in that country as Camptosar by Pharmacia, have been suspended after a higher mortality was seen with the drug versus comparator regimens. A report on the trials has been published on the New England Journal of Medicine's web site, over a month before publication in the hard copy version of the journal, because of the potential clinical significance of the findings.

Both studies were in metastatic colorectal cancer patients, an indication in which irinotecan is now considered front-line therapy, and investigated a regimen of irinotecan, 5-fluorouracil and leucovorin (developed by Saltz et al) which was recently shown to be superior to 5-FU and leucovorin alone (NEJM September 28, 2000). The regimen used in these studies is not based on the approved infusional schedule for irinotecan.

The first trial, N9741, compared irinotecan to Sanofi-Synthelabo's Eloxatin (oxaliplatin), both given in combination with 5-FU and leucovorin, as well as dual therapy with irinotecan plus oxaliplatin. The second study, C89803, compared adjuvant therapy with the irinotecan-based triple regimen to 5-FU and leucovorin alone in patients with resected stage III colon cancer. Both were conducted by the US National Cancer Institute.