Allopurinol in Subjects with Colorectal Adenoma—Response

We thank de Boer and van Bodegraven for their interest in our trial (1) and the important considerations about the potential use of allopurinol for the prevention of colorectal cancer (CRC) in subjects with inflammatory bowel disease (IBD).

Allopurinol has been used in the treatment of IBD for several years, and recent data (2, 3) further underline the efficacy of this drug to increase the compliance of thiopurine for the maintenance of remission of IDB, allowing lower doses of thiopurine.

A second most relevant aspect in the field of cancer prevention is the potential of preventing CRC in high-risk patients, including IBD. IBD has been associated with CRC in several epidemiologic studies (4–6). Allopurinol has been shown to be associated with lower risk of CRC in subjects with gout (7) and with better survival in advanced CRC (8, 9).

Thus, allopurinol should be tested as a cancer preventive agent in patients with IBD in controlled clinical trials. We firmly believe that the development of old drugs with mature safety data is an important avenue of research in cancer prevention. Paradigmatic examples of this area are aspirin and metformin. Retooling old and inexpensive agents with long postmarketing surveillance that have accumulated sound evidence of cancer preventive potential can have huge public health implications. Moreover, as molecular medicine comes of age, these old drugs are being shown to be targeted agents that act through recently discovered and crucial mechanisms of proliferation control, including stimulation of AMPK and inhibition mTOR pathways (10).

A key point not to be overlooked is the low cost of these old drugs: in the era of the most expensive targeted therapies for the treatment of advanced cancer, cancer prevention could be cost effective 2 times: first for being potentially able to avoid a costly cancer therapy and second for using low cost drugs.

See the original Letter to the Editor, p. 368