Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis

RCT (n=171) found that incidence of disease progression was not significantly lower with combination of eflornithine and sulindac compared with either drug alone [18 of 56 (32%) combination vs. 22 of 58 (38%) sulindac and 23 of 57 (40%) eflornithine group].

SPS commentary:

Cyclooxygenase (COX) and ornithine decarboxylase (ODC) are enzymes that are normally negatively regulated by adenomatous polyposis coli and are overexpressed in tumour tissue. Trials of pharmacologic prevention with NSAIDs to prevent or delay the progression of polyps in patients with familial adenomatous polyposis or to prevent the development of advanced adenomas in patients with sporadic polyps have yielded limited benefit. A 3-year randomized, placebo-controlled trial of a combination of eflornithine, an irreversible inhibitor of ODC, plus low-dose sulindac for the prevention of sporadic adenomas showed that the risk of subsequent advanced colorectal adenomas was more than 90% lower with combination therapy than with placebo; and another trial reported that celecoxib and eflornithine enhanced regression of total polyp burden. These clinical data provided proof of concept that polyamine inhibition combined with NSAIDs as a potential approach for pharmacologic prevention could delay progression of familial adenomatous polyposis.

The researchers note that despite the difficulties associated with anticipating the incidence of progression among patients with rare diseases, their data showed that the eflornithine–sulindac group had the expected result with an incidence of 32%, however, the incidences in the eflornithine and sulindac groups were much lower than the predicted 70% estimated on the basis of a literature review, which may have contributed to the lack of significance between the eflornithine–sulindac and either monotherapy group.


New England Journal of Medicine