For men younger than 50 with prostate cancer, undergoing a radical prostatectomy can greatly increase their chances for long-term survival, according to a new study from Henry Ford Hospital.

Results from the study done on the National SEER database show that the surgical procedure improves the 5-, 10-, 15- and 20-year survival for younger patients, when compared with other standard treatments such as radiotherapy or watchful waiting.

“When given the choice between surgery, watchful waiting or external beam radiotherapy, patients younger than 50 with moderately and poorly differentiated prostate cancers have better long-term overall and cancer-specific survival when they opt for surgery,” says study author Naveen Pokala, M.D., an urologist with Henry Ford Hospital.

Based on findings from the study, Dr. Pokala and co-author Mani Menon, M.D., director of Henry Ford’s Vattikuti Urology Institute, strongly recommend retropubic radical prostatectomy - a surgical procedure that removes the entire prostate gland plus some of the tissue around it - as the treatment of choice for prostate cancer patients under the age of 50.

Prostate cancer affects one in six men in the United States during his lifetime, but according to the American Cancer Society only one in 35 will die of it.

Although the majority of all prostate cancer are diagnosed in men older than 65, its prevalence is growing among men younger than 50. In fact, about one in 10,000 men under the age of 40 will be diagnosed this year with prostate cancer.

To determine which treatment option offers the best chance for long-term survival for younger prostate cancer patients, Pokala and Menon studied more than 8,200 men under age 50 with prostate cancer.

Among the study group, 73 percent were white and about 22 percent were black. The mean age was 46, and over 70 percent had moderately and 22 percent had poorly differentiated cancers. Of the patients, 1,065 were managed with no definitive treatment (watchful waiting); 6,614 (79.9 percent) with radical retropubic prostatectomy; and 600 with external beam radiotherapy.

The cancer-specific survival in the NDT group was 78 percent at 16 years, in the radiation group was 63 percent at 17 years; and 94 percent in the radical prostatectomy at 21 years. On a subset analysis the outcome was significantly better after radical prostatectomy in patients with moderately and poorly differentiated prostate cancer.

Overall, the study shows the 5-year, 10-year, 15-year and 20-year overall survival and cancer specific survival is significantly increased in patients who were less than 50 years of age with moderately and poorly differentiated cancers in the surgery group.

The results were presented in Chicago at the recent American Urological Association’s annual meeting.

Source:
Dwight Angell

Henry Ford Health System

Ligand Pharmaceuticals Incorporated (NASDAQ:LGND) announced the initiation of a Phase I clinical trial with LGD-4033, a next-generation selective androgen receptor modulator (SARM) designed to provide the benefits of androgen receptor stimulation on skeletal muscle and bone without the side effects of currently marketed androgens. The Phase I study will evaluate the safety, tolerability and pharmacokinetic profile of orally administered LGD-4033.

In preclinical studies, LGD-4033 demonstrated a highly tissue-selective profile with increased skeletal muscle mass and bone mineral density while largely sparing the prostate in males and masculinizing effects in females. Extensive preclinical studies with LGD-4033 demonstrate the following:

- LGD-4033 is highly selective for the androgen receptor.

- Gene transcriptional regulation assays using muscle or bone cells demonstrate that LGD-4033 is a potent, full agonist producing efficacy comparable to the natural steroidal androgen dihydrotestosterone.

- In repeat oral dosing studies LGD-4033 increases skeletal muscle mass.

- In the ovariectomized rat model of post-menopausal osteoporosis, LGD-4033 had anabolic activity in cortical bone, significantly increasing cortical bone formation rates, bone strength and bone density. LGD-4033 also suppressed bone turnover at cancellous bone sites, leading to an increase in lumbar spine bone density and strength.

- In repeat oral dosing studies, LGD-4033 is a weak partial agonist on the prostate gland with more than 500-fold selectivity for muscle versus prostate. This indicates an absence of the prostatic hypertrophy that occurs with the currently marked androgens.

“LGD-4033 has shown an excellent SARM profile to date in terms of efficacy, potency and selectivity, and it is potentially a novel therapeutic for muscle and bone-related disorders such as cachexia and frailty,” said John L. Higgins, President and Chief Executive Officer of Ligand Pharmaceuticals. “This program is another example of how the success of Ligand’s research platform, which so far includes five approved drugs, allows us to continue investing in and strengthening a portfolio of promising candidates to address major clinical needs and commercial market opportunities.”

SARM Program

SARMs are designed to elicit the desired biological effects without the undesirable side effects or potential risks over time of currently marketed androgens, providing a wide range of opportunities for the treatment of many diseases and disorders in both men and women. Tissue-selective androgen receptor agonists may provide utility in the treatment of a number of medical conditions, including frailty, cachexia, osteoporosis, sexual dysfunction and hypogonadism. Ligand has discovered orally active, non-steroidal SARM compounds, such as LGD-4033 and LGD-3303, based on tissue-specific gene expression and other functional, cell-based technologies.

Source
Ligand Pharmaceuticals