Phellodendron amurensebark extract (Nexrutine®) has shown a favorable effect on prostate cancerin vivoandin vitro. We evaluated its tolerance in patients undergoing surgery or radiation for prostate cancer. Patients received Nexrutine® orally (500 mg tid) either 1 to 2 months preoperatively or 1 to 2 months prior to and with radiation therapy. Common Terminology Criteria for Adverse Events were used to measure tolerance. In total, 21 patients (9 surgery and 12 radiation) underwent treatment. During the Nexrutine® alone component, there were two transient grade 3 toxicities (hypokalemia and urinary incontinence). There was no grade 4 toxicity. For the combined Nexrutine® and radiation component, no additional patients suffered a grade 3 toxicity. All the toxicities were transient. By the end of the neoadjuvant treatment, 81% of the patients had a decline in prostate-specific antigen. This is the first report of patients with prostate cancer being treated withP. amurensebark extract, and it was very well tolerated. Toxicities were minimal and self-limited. This compound can be safely used in further evaluation of a treatment effect on cancer. Copyright © 2014 John Wiley & Sons, Ltd.