BERKELEY, CA (UroToday.com) - If we go back to our medicinal roots (unintended, but fortuitous pun), up until the late 1800s almost all the available medicinals were from plants. Recognizing that, in the evolution of the drug industry the early goals were to extract the active compounds from their natural sources. For example, it was recognized that chewing white willow bark offered anti-inflammatory and pain relief effects. Subsequently, salicyclic acid (the precursor to aspirin) was successfully extracted from the bark. In oncology, one famous example is the taxanes, whose origins go back to the Taxus brevifolia tree. Certainly, efforts are continuing to find unique chemical compounds in plants and animals. Unfortunately, in the naturopathic “medicine“ world (“alternative medicine”), given that there is no federal mandate to do so as with the pharmaceutical industry, there is often very little scientific support for the claims of effect that are made. That hasn’t prevented it from being a billion dollar annual industry. The unfortunate result, there hasn’t been much of a need for those purveyors to prove anything, tainting the field with an anti-scientific flavor. Given history though, it is clear that there are likely other effective plant compounds out there. The challenge is to find them, but given the lack of financial impetus to do so, there have not been a lot of industry driven trials. What is remarkable, though, is the vast number of basic science research that has been ongoing. There are many promising findings on the cellular and animal level; they just have not been taken to trial. The appeal of the “natural products” is that they are generally widely available and widely used (often with a long history).
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Our interest in the phellodendron amurense extract (Nexrutine®) is from some work done in the mouse model that showed a potential suppressive effect in prostate cancer. This raised the question for us as to whether there would be any further therapeutic benefit with radiation. We were fortunate to obtain institutional funding, and in a TRAMP mouse model, we found that the combination of the extract and radiation had a dramatic effect on prostate cancer. Given that there was already a clinical safety record with Nexrutine®, it appeared to be a “no lose” situation to take this to human trial. Our immediate goal was to confirm in a detailed way the safety of the drug, with and without radiation therapy. We obtained limited institutional funding and the result is what we published. It is pretty clear that it is well tolerated, which is the endpoint of a phase II study. Our goal was for about twice as many patients, with the hope of getting at least some feel for efficacy. Unfortunately, we ran out of funding before we could get there. While obviously not as dramatic as was seen in the mice model, there are some intriguing little blips (i.e., PSA response). Whether these would have been confirmed in more patients is uncertain. It does raise the point that there are many plant products worth looking at, it is just a matter for those that dole out the limited research sources (i.e., the NCI and the associated well-funded institutions) to see their importance and seek to fund further trials of this kind.
- Ghosh R, Graham H, Rivas P, Tan XJ, Crosby K, Bhaskaran S, Schoolfield J, Banu J, Fernandes G, Yeh IT, Kumar AP. Phellodendron amurense bark extract prevents progression of prostate tumors in transgenic adenocarcinoma of mouse prostate: potential for prostate cancer management. Anticancer Res. 2010 30: 857-65, 2010.
- Robson C, Ganapathy M, Swanson G, Papanikolaou N, Rivas P, Hanes M, I-Tien Y, Ghosh R, and Kumar A. Phellodendron amurense bark extract as an adjuvant for prostate cancer radio-therapy. AACR Meeting Abstracts, Apr 2009; 2009: 3005.
Gregory P. Swanson, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Clinical Professor of Radiation Oncology, Radiology and Urology
UT Health Science Center San Antonio
Professor of Radiology
Texas A&M College of Medicine