Intermittent dosing regimens of aspirin and naproxen inhibit azoxymethane-induced colon adenoma progression to adenocarcinoma and invasive carcinoma

Chronic use of aspirin and related drugs to reduce cancer risk is limited by unwanted side effects. Thus, we assessed the efficacy associated with different dosing regimens of aspirin and naproxen. Azoxymethane (AOM)-rat colon cancer model was used to establish the pharmacodynamic efficacy of aspirin and naproxen under different dosing regimens. Colon tumors were induced in rats (36/group) by two weekly doses of AOM. At the early adenoma stage, rats were fed diets containing aspirin (700, and 1,400 ppm) or naproxen (200 and 400 ppm), either continuously, one week on/one week off, or three weeks on/three weeks off, or aspirin (2,800 ppm) three weeks on/three weeks off. All rats were euthanized 48 weeks after AOM treatment and assessed for efficacy and biomarkers in tumor tissues. Administration of aspirin and naproxen produced no overt toxicities. Administration of different treatment regimens of both agents had significant inhibitory effects with clear dose-response effects. Aspirin suppressed colon adenocarcinoma multiplicity (both invasive and non-invasive) by 41% (p