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Posted by on Jul 14, 2014 in Prostate cancer | 1 comment

In a nutshell

This study evaluated the use of prostate-specific antigen doubling time as a marker of effectiveness of the personalized peptide vaccination for castration-resistant prostate cancer.

Some background

Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (progression despite treatment to reduce the levels of male hormone). Cancer vaccination involves separating small proteins from cancer cells and immunizing cancer patients against those proteins, in the hope of stimulating an immune reaction (by T-cells or B-cells of the immune system) that could kill the cancer cell. However, because of delayed immune responses, its clinical benefits are not well captured.

 Several markers for evaluation of the cancer vaccine in castration-resistant prostate cancer, including prostate-specific antigen doubling time, are currently sought. Prostate specific antigen (PSA) is a molecule produced by the prostate, and its levels are elevated in patients with prostate cancer. PSA doubling time is the length of time it takes for PSA levels to double.

The purpose of this study was to assess the PSA reactions and immune responses, as well as the effectiveness, safety, and markers of personalized peptide (small protein) vaccination in progressive castration-resistant prostate cancer.

Methods & findings

100 patients with a diagnosis of prostate cancer and progressive disease defined as at least two consecutive increases in PSA were evaluated. Of the 31 candidate vaccination proteins, 2 – 4 were used based on an evaluation of the patient’s immunological response to the candidates. All patients received at least 1 vaccination with the average number of vaccinations being 16.

Personalized peptide vaccination was generally well tolerated with an average survival time of 18.8 months. The most frequent adverse events were local redness and swelling at injection sites, bone pain, hypoalbuminemia (abnormally low levels of the protein albumin in the blood), lymphocytopenia (abnormally low levels of lymphocytes or white blood cells), appetite loss and fatigue which were grade 1 or 2 (mild to moderate) in most cases.

 49% of patients exhibited some decrease in PSA from the beginning of the study, ranging from 1.9% to 99.6%. A confirmed PSA decrease of 50% or greater was observed in 22% of patients during the follow-up with an average time to decline of 4 months and an average duration of decline lasting 3 months. The average PSA doubling time before the vaccination was 2 months compared to 3.89 months after vaccination. 56% of patients displayed at least a 2-fold increase in PSA doubling time compared to pre-treatment PSA doubling-time.

Positive IgG (a protein that protects the body from infection) responses during the vaccination period were observed in 79% of patients. Protein-specific T-cell responses were apparent in 43% of patients at the 6th vaccination. These were positively correlated to PSA doubling time.

Prolongation of PSA doubling-times, positive IgG response, good performance status at the beginning of the study and low PSA levels were factors favorably associated with overall survival.

The bottom line

PSA doubling-time could be an appropriate marker for evaluation of the clinical benefit of the personalized peptide  cancer vaccine.

Published By :

BMC cancer

Date :

Dec 30, 2013

Original Title :

A phase II trial of personalized peptide vaccination in castration-resistant prostate cancer patients : prolongation of prostate-specific antigen doubling time.

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