Irinotecan Shown to Be Effective Against Colorectal Cancer

Irinotecan {Campo} a new anticancer agent developed by Rhone -PoulencRorer Inc, demonstrates significant activity in the treatmentof advanced colorectal cancer, according to research presentedat the Eighth Annual European Cancer Conference (ECCO-8) in Paris.

"Phase II clinical trials conducted in Europe, the UnitedStates, and Japan confirm that Campto has significant activityin advanced colorectal cancer," said Dr. Jean-Pierre Armandfrom the Institute Gustave Roussy in France, one of the principalclinical investigators of the irinotecan study. "There isa growing body of research that indicates Campto is effectiveboth as a first- and a second-line treatment. No other currentlyavailable anticancer drug has demonstrated comparable efficacyas a second-line treatment for advanced colorectal cancer. Asa first-line treatment, irinotecan's efficacy can be comparedto 5-fluorouracil (5-FU) with folinic acid, the standard chemotherapytreatment."

Irinotecan is now approved and available in France for the treatmentof advanced colorectal cancer that has failed to respond to standardchemotherapy with 5-FU and folinic acid.

Clinical Trial Results

Patients experienced a clinically significant response to irinotecanin a multicenter phase II clinical trial completed in France andreported at ECCO-8. Investigators enrolled 213 patients, 178 ofwhom were evaluable. A total of 130 patients had experienced diseaseprogression despite treatment with 5-FU (irinotecan was thus usedas second-line therapy in these patients), whereas 48 had notpreviously received chemotherapy (first-line therapy). Irinotecanwas administered as a 350-mg/m² intravenous infusion every3 weeks (one treatment cycle).

The overall response rate was 18%. Twenty-eight patients had apartial response (defined as at least a 50% reduction in measurabletumors), and four patients experienced a complete response (totaldisappearance of all measurable signs of cancer). The median durationof response was 9.1 months, and median survival was 10.6 months.

"Achieving a significant response for an average period ofup to 9 months is impressive," said Dr. Philippe Rougier,also a principal investigator at the Institut Gustave Roussy."Importantly, patients who had progressed during a pretreatmentof 5-FU also showed treatment response while on Campto, thus indicatingthe lack of cross-resistance between the two treatments."

"Campto represents a true advance in the treatment of advancedcolorectal cancer, an area where advances have been few and farbetween. Historically, patients who failed on 5-FU, the standardtreatment for colorectal cancer, had no other therapy alternatives,"said Dr. Armand.

While about 50% of patients are cured by surgery, the other halfdevelop metastatic disease and require treatment with an anticancerdrug. For four decades, 5-FU has been the only effective agentin the treatment of advanced colorectal cancer, with about 10%to 25% of patients experiencing a clinical response. In most cases,however, the disease progresses despite 5-FU treatment.

Irinotecan acts as an inhibitor of topoisomerase I, an enzymeessential for cell division. Inhibition of this enzyme's activitykills cancer cells. As is often seen with cancer chemotherapyagents, side effects of irinotecan have been observed during clinicaltrials, such as neutropenia and moderate to severe diarrhea. Theseeffects can be controlled through concomitant medications, suchas antibiotics and loperamide.

An additional clinical trial of irinotecan involving patientswho failed to respond while on 5-FU treatment has been completedin Belgium, the United Kingdom, the Netherlands, Germany, Switzerland,Austria, and Greece. Advanced clinical trials have begun or arebeing planned in most European countries.