Hollis-Eden reports additional findings from Phase I/II prostate cancer study

The new findings show that Apoptone treatment significantly reduced tumor volume (p < 0.05), and delayed tumor-doubling time relative to that in vehicle-treated animals. An analysis of tumor samples from these mice also demonstrated that Apoptone lowered levels of androgen receptor protein and significantly reduced gene expression relative to the vehicle controls (p < 0.05). In addition, tumors in mice treated with Apoptone had reduced levels of testosterone and dihydrotestosterone (DHT) relative to the vehicle-treated animals, suggesting that Apoptone suppressed hormone synthesis directly within the tumors. These preclinical results demonstrate that Apoptone significantly inhibits tumor growth in this model of castration-resistant prostate cancer, apparently by suppressing critical hormones and receptors necessary for tumor cell survival. Data were also presented from a separate model of prostate mediated bone disease, where C4-2B castration-resistant tumor cells were implanted directly into the tibia of castrated SCID mice. Apoptone treatment significantly lowered the tumor bearing tibia weight and reduced PSA levels relative to the vehicle-treated animals (p < 0.05). The Phase I/II clinical trial, now currently enrolling patients, is a dose escalation trial currently scheduled to evaluate up to four different dosing groups to determine the maximum tolerated dose. Primary objectives of the study are to determine the safety, tolerance, pharmacokinetics and potential activity of the compound over 28-day dosing cycles in up to 44 patients with advanced prostate cancer who have failed hormone therapy and at least one round of taxane-based chemotherapy. Bruce Montgomery, associate professor, division of oncology, University of Washington, said: "Apoptone appears in preclinical studies to suppress the androgen receptor while also inhibiting the ability of castration-resistant tumor cells to synthesize their own androgens. The potential that Apoptone acts to cut off the tumors' fuel supply and cause programmed cell death is completely different from the effect of classical hormonal blockade therapy."