Complementary and alternative medicines in prostate cancer: From bench to bedside? "Beyond the Abstract," by Samuel Klempner, MD

BERKELEY, CA (UroToday.com) - In our recent article, we sought to discuss the common clinical question of the role of complementary and alternative (CAM) supplements in the treatment of prostate cancer (PCa). Despite the increasing frequency of CAM usage among all cancer patients, the molecular mechanisms underlying their use and even their overall effectiveness remain poorly understood. The summary table below outlines the molecular targets and major barriers to clinical usage for the most common CAM therapies used by PCa patients.

Table 1.  Comparison of human and cell line/xenograft data for several common CAM therapies used by prostate cancer patients.

CAM Substance

Targets

Cell line concentration(s)

Achievable human plasma concentration

Human Clinical Trials

Barriers to Clinical Translation

Paper Reference

Pomegranate Extract (Punicalagin)

NF-kB, p21, p27

10-100 ug/mL

0.06 uMol/L

(~ 0.06 µg/mL)

YES, phase III in PSA-only recurrence

High cell line concentration,         Bioavailability

21, 22

Green Tea (EGCG)

AR signaling, NF-kB, Bcl-2

10-100 uM

0.4 - 0.8 uM  (0.9 - 3.3 ug/mL)

YES, phase II neoadjuvant, PSA-only recurrent disease

Variable metabolism, absence of biomarkers, side effects at required doses

34, 39-42

Curcumin

NF-kB, MDM2, PI3K/Akt/mTOR

25-100 uM

0.5 - 0.75 nM (0.19-0.28 ug/mL)

YES, phase II pancreatic, neoadjuvant rectal with Capecitabine

High cell line concentrations needed, Low bioavailability

66, 67

Resveratrol

AR signaling, SIRT1, FOXO genes, Akt

50-150 uM

2 uM (0.5 ug/mL)

YES, multiple bioavailability studies

Low bioavailability

95, 96

Muscadine

Akt, proteasome, DJ-1

10-20 ug/mL (0.01 uM)

N/A

YES, phase I/II in PSA-only recurrence

Low bioavailability

101

Silibinin

IGF-1, IGFBP-3, ?VEGF

50-100 ug/mL

4.0 - 19.7 uM (1.9 - 9.4 ug/mL)

NONE

Low bioavailability

112, 113

Combination Therapy

Multiple

N/A

N/A

YES

Drug-CAM interactions

119 - 125

The above table demonstrates that for many of the agents currently in use as CAMs, it is unlikely that serum levels can be achieved that are commensurate with their reputed mechanism of action. We therefore believe that the scientific and clinical rigor expected of FDA-approved therapies should be applied to the CAM field. A coordinated effort between preclinical and clinical work is needed to improve our understanding. Both concentrations at which effective in-vitro target inhibition occurs and whether or not these concentrations are achievable in-vivo are important steps prior to more advanced clinical investigations. Further, reliable assays are needed to measure CAM concentrations in order to obtain further pharmacokinetic data.

There are several ongoing clinical trials (NCT00719030, NCT00685516, and NCT00844792) which also seek to address the important question of measuring tissue CAM concentrations in men undergoing prostatectomy, and these trials will hopefully demonstrate increased concentrations within malignant cells. While it is unlikely that CAM monotherapy will be effective in treating PCa, and other malignancies, the possibility of CAM adjuncts to standard therapies is highly possible, and this is an important area of ongoing investigation.

Despite the promising preclinical and early clinical phase data we do not routinely recommend CAM therapies in prostate cancer outside of a clinical trial.

 


Written by:

Samuel Klempner, 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.

Research and Clinical Fellow
Hematology-Oncology
Beth Israel Deaconess Medical Center
Boston, MA USA 


 

Complementary and alternative medicines in prostate cancer: From bench to bedside? - Abstract

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