Sulindac-erlotinib limits polyp burden in familial adenomatous polyposis

Reuters Health Information: Sulindac-erlotinib limits polyp burden in familial adenomatous polyposis

Sulindac-erlotinib limits polyp burden in familial adenomatous polyposis

Last Updated: 2018-02-13

By Will Boggs MD

NEW YORK (Reuters Health) - Combination treatment with sulindac and erlotinib reduces colorectal polyp burden in patients with familial adenomatous polyposis (FAP), according to a secondary analysis of the FAPEST study.

"No other agent to date has shown such a strong polyp regression effect in FAP," Dr. N. Jewel Samadder from Mayo Clinic, Phoenix, Arizona, told Reuters Health by email. "Though the standard of care for management of FAP currently involves annual endoscopy/colonoscopy followed by surgery, we can now foresee a time when a chemoprevention approach may be able to transition the management of these patients to chronic medical therapy, reducing the need for invasive and morbid surgery."

Earlier results from FAPEST showed that this combination of COX (sulindac) and EGFR (erlotinib) inhibition resulted in a 71% reduction in duodenal polyp burden after only six months of treatment.

For the current analysis, Dr. Samadder and colleagues assessed the effect of sulindac and erlotinib on colorectal adenoma formation and regression in 82 patients with FAP. The findings were reported online February 8 in JAMA Oncology.

Patients randomized to receive sulindac-erlotinib experienced a median decrease of 27 colorectal polyps from baseline, compared with a 2-polyp decrease from baseline in the placebo group, a significant 69.4% change-from-baseline advantage of the combination therapy.

Results persisted in the per-protocol analysis (a 28-polyp difference among patients with an intact colorectum and a 5.5-polyp difference among patients with ileal pouch anal anastomosis, both in favor of sulindac-erlotinib).

Common adverse events in the treatment group included an erlotinib-induced acneiform-like cutaneous eruption (68%), oral mucositis (32%), diarrhea (24%), and nausea (24%). Grade 2 or 3 adverse events were twice as common with treatment than with placebo (44% vs. 22%).

Nearly three-quarters of patients (73%) in the treatment group required erlotinib dose reductions, and just over half (54%) required sulindac dose reductions.

"This clinical trial provides a proof of concept regarding chemoprevention for colorectal and duodenal neoplasia in patients with FAP," Dr. Samadder said. "There is a new clinical trial - Erlotinib Hydrochloride in Reducing Duodenal Polyp Burden in Patients With Familial Adenomatous Polyposis, NCT02961374 ( - that has now been approved by the National Cancer Institute and is open for recruitment. This is a multicenter trial that will test a weekly dosing regimen of erlotinib alone to see if polyposis (colorectal and duodenal) will decrease while reducing the side effect profile."

"FAP patients should only receive erlotinib for 'chemoprevention' within the confines of a clinical trial at this time," she said. "I would recommend physicians interested in having their patients assessed for erlotinib chemoprevention consider referral to one of the sites participating in the trial and/or speaking with a clinical expert in this area."

"Since FAP is genetic, 50% of an affected individual's children will have the same condition, and most parents will do anything to prevent their children going through the same hardship they have faced," Dr. Samadder said. "These clinical trials aim to offer hope to the current individuals with FAP and to their children that a medical management option will replace the need for complex surgeries."


JAMA Oncol 2018.

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