Phase IIa Clinical Biomarker Trial of Dietary Arginine Restriction and Aspirin in Colorectal Cancer Patients.

After potentially curative treatment, colorectal cancer (CRC) patients remain at high risk for recurrence, second primary CRC, and high-risk adenomas. In combination with existing data, our previous findings provide a rationale for reducing tissue polyamines as tertiary prevention in non-metastatic CRC patients. The goal of this study was to demonstrate rectal tissue polyamine reduction in optimally treated stage I-III CRC patients after intervention with daily oral aspirin + dietary arginine restriction. A single-institution phase IIa clinical trial was conducted. Patients were treated with aspirin 325 mg/day and an individualized dietary regimen designed to reduce arginine intake by ≥30% over a 12-week study period. Dietary intake, endoscopy with rectal biopsies, and phlebotomy were performed pre- and post-intervention. The primary endpoint was to demonstrate ≥50% decrease in rectal tissue putrescine levels from baseline as a measure of polyamine reduction in the target tissue. Twenty eligible patients completed the study. After study intervention, mean dietary arginine intake decreased from 3.7 g/day ± 1.3 SD to 2.6 g/day ± 1.2 SD (29.7% decrease, p < 0.02 by Sign test). Mean plasma arginine levels decreased from 46.0 ng/mL ± 31.5 SD at baseline to 35 ng/mL ± 21.7 SD ( p < 0.001). Rectal tissue putrescine levels were 0.90 nMol/mg-protein pre-intervention and 0.99 nMol/mg-protein post-intervention ( p < 0.64, NS). No significant differences were observed for the other tissue polyamines investigated: spermidine ( p < 0.13), spermine ( p < 0.21), spermidine:spermine ratio ( p < 0.71). Among CRC survivors, treatment with daily oral aspirin and an individualized dietary arginine restriction intervention resulted in lower calculated dietary arginine intake and plasma arginine levels but did not affect rectal tissue polyamine levels.