A “promising avenue” for preventing colorectal cancer has been discovered
by US researchers. Combining a non-steroidal anti-inflammatory drug with an
epidermal growth factor receptor (EGFR) kinase inhibitor “afforded remarkable
protection” from intestinal neoplasia in a mouse model.
Dr Christopher Torrance (Howard Hughes medical institute and Johns Hopkins oncology
centre, Baltimore, Maryland) and colleagues tested the NSAID sulindac with an
EGFR kinase inhibitor, EKB-569. Mice with a predisposition to developing intestinal
polyps were treated for 60 days, after which their intestinal tracts were removed
and the number of intestinal polyps counted. High doses of sulindac (20mg/kg/day)
reduced intestinal polyps by about 70 per cent while low doses (5mg/kg/day)
had no effect. EKB-569, when given alone, reduced polyp formation by 87 per
cent. However, a combination of EKB-569 and 5mg/kg/day sulindac reduced the
number of polyps formed by over 95 per cent. Of the control group, 100 per cent
developed tumours while 47 per cent of the combination group had no tumours
at all. Further experiments suggested that the drugs prevented tumour progression
rather than tumour initiation (Nature Medicine 2000;6:1024).
Commenting on the paper (ibid, p974), Dr Rajnish Gupta and Dr Raymond DuBois
(Vanderbilt university medical centre, Nashville, Tennessee) note that the results
show that the combination of sulindac and EKB-569 allowed a 75 per cent reduction
in the dose of sulindac which might minimise its long-term toxicity. They say
that this may lead to the eventual development of effective combination regimens
for cancer prevention in humans. However, they caution that the safety of long-term
use of an EGFR kinase inhibitor is unknown. Combining an EGFR kinase inhibitor
with a COX-2 selective inhibitor might achieve similar or better results for
prevention of tumour formation, they add.