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Monitoring is crucial for patients receiving irinotecan combination

The combination of bolus-therapy irinotecan (Campto), fluorouracil and calcium folinate (calcium leucovorin) for the treatment of colorectal cancer is associated with an excessive rate of early deaths compared with other treatment combinations, say American researchers.

In a letter to the New England Journal of Medicine, Dr Daniel Sargent of the Mayo Clinic in Rochester, Minnesota, and colleagues say that the regimen, which improves survival rates in advanced colorectal cancer (see PJ, April 8, 2000, p533 and November 4, 2000, p677), should continue to be a treatment option, but that patients receiving this combination should be closely monitored.

They report data from two studies that compared the use of irinotecan, fluorouracil and calcium folinate with regimens of oxaliplatin, fluorouracil and calcium folinate, of oxaliplatin and irinotecan, and of fluorouracil and calcium folinate. They say that the data reveal an imbalance in the number of deaths occurring within 60 days of the start of treatment.

Deaths from any cause within 60 days of start of treatment

In the first trial, 14 deaths occurred in the group of patients given irinotecan, fluorouracil and calcium folinate (n=289) compared with five deaths in patients given the other regimens (oxaliplatin, fluorouracil and calcium folinate, n=277, and oxaliplatin and irinotecan, n=275). In the second trial, 14 deaths occurred in the group of patients given irinotecan, fluorouracil and calcium folinate (n=635) compared with five deaths in the group receiving fluorouracil and calcium folinate (n=628).

The researchers comment that in the first trial, most of the deaths (13 out of 14) occurred during, or immediately after, the first six-week cycle of chemotherapy, and that 12 of the 14 deaths had several characteristics in common. These included neutropenia, sepsis, and dehydration from diarrhoea, nausea, and vomiting (2001;345:144).

In response to the letter, Dr Jonathan Ledermann of University College London, and colleagues comment that the incidence of neutropenia and diarrhoea associated with this regimen is higher when fluorouracil is delivered as a bolus rather than as an infusion.

They describe a regimen combining irinotecan with high doses of infused fluorouracil that they have found to be safe (ibid, p145).

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