Tag: Prostate Cancer

Prolaris is a molecular diagnostic tool developed by Myriad Genetics, Inc. This 46 gene panel is capable of predicting  aggressiveness of prostate cancer and can be used in conjunction with Gleason score and PSA. By measuring the  expression level of genes involved with cell cycle progression, this test is able to differentiate indolent from aggressive prostate cancers and therefore predict disease outcome.

In a retrospective analysis of 366 patients who had undergone radical prostatectomy and 337 patients with clinically localized prostate cancer, this gene panel was able to give a favorable and unfavorable score to patient subsets and thus predict clinical outcomes. This prognostic information will allow clinicians to recommend appropriate therapy at the time of diagnosis of prostate cancer.

So we have gene signature assays for breast cancer, colon cancer, lung cancer (oncoprescribe blog) and now for prostate cancer as well. In the end, patients benefit.

Abiraterone is a steroidal agent and inhibits CYP17A, an enzyme necessary for the production of androgen precursors and subsequently testosterone. It is capable of inhibiting testosterone production both in the adrenals as well as the testes.

Data from a recent phase III trial was presented at the ESMO meeting and in this International trial involving 1,195 patients, Abiraterone plus a steroid was compared with placebo plus steroid in patients with CRPC (Castrate-Resistant Prostate Cancer) who had failed chemotherapy with Docetaxel. Following an interim analysis and upon recommendation from the Independent Data Monitoring Committeee, the study had to be unblinded, as there was a significant improvement in overall survival in the group receiving Abiraterone. With the availability of several new agents for the treatment of CRPC, it may be important to properly sequence these available drugs to get the best of each treatment intervention and thus improve long term survival with limited toxicity.

Cabazitaxel is a microtubule inhibitor approved for the treatment of patients with CRPC (Castrate-Resistant Prostate Cancer) who have progressed on Docetaxel. This agent in a randomized phase III trial (TROPIC) demonstrated a significant improvement in Overall Survival (OS) compared with Mitoxantrone, with a 30% reduction in the risk of death. We now have another option for the treatment of CRPC which until not too long back was considered as a disease for which chemotherapy was not effective.

This year 2 new agents have been approved for the treatment of Castrate-Resistant Prostate Cancer – Sipuleucel-T and Cabazitaxel. Sipuleucel-T is composed of autologous antigen-presenting cells (APC’s) from the patient, cultured with a fusion protein PA2024 (Prostate Acid Phosphatase-PAP linked to granulocyte/macrophage colony-stimulating factor). Prostatic Acid Phosphatase (PAP) is an antigen expressed in most prostate cancers. When administered, Sipuleucel-T an autologous active cellular immunotherapy stimulates T cell immunity against PAP and thus the prostate cancer cells. This agent demonstrated improvement in median survival and is best suited for those patients who are asymptomatic or have minimal symptoms with CRPC. It is important to note that this agent is given as three infusions 2 weeks apart and one may not see a drop in the PSA or improvement in the bone scan findings until after three months following treatment. For this reason it is best to consider this agent well before chemotherapy with docetaxel is planned. The number of patients who can be treated with this agent presently is limited due to various barriers associated with the processing of autologous Antigen Presenting Cells. It is important to realize that steroids may counter the T cell response associated with this agent and therefore should be avoided.