FDA Approves Irinotecan as First-Line Therapy for Colorectal Cancer

The US Food and Drug Administration (FDA) has approved irinotecan (Camptosar) as first-line therapy for patients with metastatic colorectal cancer in conjunction with fluorouracil (5-FU) and leucovorin. The approval follows unanimous recommendation by the FDA’s Oncologic Drugs Advisory Committee (ODAC). The Committee’s recommendation was based on survival data from two prospective, independent studies demonstrating the potential of irinotecan for extending colorectal cancer patients’ lives when used as first-line treatment.

Both Trials Demonstrate Similar Benefits

Data from these two well-controlled, international (one North American, one European), phase III trials suggested significant improvements in objective tumor response rates, time to tumor progression, and prolongation of survival for the regimen of irinotecan and 5-FU/leucovorin, as compared with 5-FU/leucovorin alone.

“It is really exciting that the North American and European trials independently suggest the same basic benefits. The addition of irinotecan to 5-FU/leucovorin results in a generally well-tolerated regimen with superior antitumor activity and prolonged patient survival,” said Leonard Saltz, MD, principal investigator of the North American phase III trial and associate attending physician at Memorial Sloan-Kettering Cancer Center.

The trials also used the well-validated European Organization of Research and Treatment of Cancer (EORTC) Quality of Life questionnaire to measure such indicators as general health status and role functioning and such symptoms as pain. Questionnaire data showed that the addition of irinotecan to 5-FU and leucovorin did not compromise prespecified quality-of-life indicators for patients in either study.

“We are pleased that an additional treatment option is available for the treatment of colorectal cancer,” said Nancy Roach, Board of Directors, Colon Cancer Alliance. “Each new drug approval gives survivors renewed hope for a longer and better quality of life.”

Adverse Events

In the North American phase III trial, diarrhea, nausea, and vomiting occurred more commonly in patients receiving irinotecan and 5-FU/leucovorin than in those given 5-FU/leucovorin alone. However, less mucositis and less severe neutropenia were associated with the irinotecan-containing regimen.

Irinotecan is associated with both early (during or shortly after infusion) and late (more than 24 hours after infusion) forms of diarrhea, which may be severe. Early diarrhea may be accompanied by such symptoms as sweating, flushing, and abdominal cramping, and may be treated with atropine. Late diarrhea can be prolonged and life threatening, and should be treated promptly with loperamide.

In addition to its current colorectal cancer indications, irinotecan is being studied as an adjuvant treatment option (with 5-FU/leucovorin) for earlier-stage colorectal cancer through a National Cancer Institute–sponsored intergroup study.