Prostate cancer APC-8015
The large majority of prostate cancers are hormone-dependent, and if they can be caught early and treated while they are still androgen-responsive then progression to hormone refractory cancer, which is very difficult to treat, can be prevented.
The large majority of prostate cancers are hormone-dependent, and if they can be caught early and treated while they are still androgen-responsive then progression to hormone refractory cancer, which is very difficult to treat, can be prevented.
Androgen production in the testes is stopped by drug-induced or surgical castration, but while this is often effective for some time, patients are still liable to progress to the refractory form of the disease in the end.
US biotech company Dendreon has been investigating the potential of a therapeutic vaccine to treat prostate cancer. Prostatic acid phosphatase is expressed only in the prostate and in prostatic tumours, and APC-8015 consists of antigen-presenting cells (APCs) that are loaded with the recombinant fusion protein PA2024. This entity is made up of prostatic acid phosphatase (PAP) linked to granulocyte macrophage colony stimulating factor, which specifically targets a receptor on the surface of the APCs. The aim is to induce a T cell mediated immune response against PAP.
Several Phase II trials have already been carried out. In one, 19 men with prostate cancer and no metastases were given APC-8015.1 Treatment was well tolerated and all the subjects had T cell proliferation responses. Median time to disease progression was 29 weeks, although it was significantly longer in those who had experienced an immune response.
Another trial looked at the prostate-specific androgen modulating effects of the vaccine in patients suffering from androgen-dependent prostrate cancer with biochemical progression.2 A total of 19 patients with non-metastatic recurrent disease who had already undergone surgical or radiation treatment were given three infusions of the vaccine, two weeks apart. Eighteen patients were evaluable for PSA response, and 13 of these demonstrated an increase in PSA doubling time, with a median increase of 62% after treatment. Median time to progression was a shade under one year.
A randomised double blind placebo-controlled Phase III trial has also been conducted. A total of 127 men with asymptomatic metastatic hormone refractory prostate cancer, no cancer-related pain and PAP-expressing tumours were given APC-8015 or placebo by infusion three times, with two weeks between each dose.3 The primary end point was objective disease progression, and once those given placebo experienced progression they were eligible for treatment with the active. Those given APC-8015 had a slightly longer time to progression - 11.1 weeks compared with 10 weeks for those given placebo. Median overall survival of the treated patients was 25.9 months, while it was 22.0 months for the placebo group. After three years one-third of those given the vaccine were still alive while only 11% of those given the placebo survived: this is the first time an immunotherapy drug has shown a survival advantage in prostate cancer. Phase III trials continue.