The development of lonidamine for benign prostatic hyperplasia and other indications.

Lonidamine (LND) is a compound originally developed as an infertility drug. By capitalizing on the unique energy requirements of many solid tumors including benign prostatic hyperplasia (BPH), LND has shown efficacy as an adjunct to either radiation or chemotherapy in the treatment of several advanced solid organ malignancies such as lung, breast, head and neck, and liver metastases. It has an excellent safety profile in over 20 years of use in Italy in thousands of cancer patients. Preliminary data suggest that it is safe and effective in the treatment of lower urinary tract symptoms associated with BPH by metabolically targeting the unique dependency of the prostate on energy production by glycolysis instead of the aerobe Krebs cycle. The observed effects include a fast reduction in serum prostate-specific antigen and prostate volume, and simultaneous improvements in symptoms and urinary flow rate. The fact that prostate cancer and high-grade prostatic intraepithelial neoplasia have similar metabolic circumstances suggests that LND might also be effective in various stages of the prostate cancer carcinogenesis.