The research, which had the participation of 1,195 patients from 147 medical sites in 13 countries over a period of 14 months, has been published in the specialized The Lancet Oncology journal. Participating from the University Hospital of Navarra were specialists at the Department of Oncology Ignacio Gil Bazo (lead researcher), José Luis Pérez Gracia (co-researcher) and nurse Elena Navarcorena (coordinator).
The trials were aimed at studying the effects of a new oral hormonal treatment – abiraterone acetate – on patients with metastatic prostate cancer resistant to castration (i.e. it continues to grow despite the hormonal therapy keeping the testosterone at very low levels) and who previously had received chemotherapy treatment.
Apart from the work with the trials, the University Hospital has had more than a year of experience with this new treatment from which about twenty patients have already benefited.
Benefits in different aspects and in all subgroups
As doctor Ignacio Gil Bazo explained, “The randomisation of the study was done in a 2 to 1 proportion. So, double the number of patients (797) was assigned to receive a daily dose of 1 gram of abiraterone acetate plus 5 milligrams of prednisone twice a day. The control group received a placebo plus prednisone. When the data was analysed, it should be pointed out that the group taking the placebo was also given prednisone, a steroid potentially active in the treatment of prostate cancer”.
As regards the results, doctor Gil Bazo underlined that these were favourable to the group receiving treatment in various aspects: “The relative risk of dying from the illness during the research was 26% less for this group. The median time for biochemical progression was also increased, i.e. for PSA progression, and from a radiological perspective, there was an increase in the average period of time with no new lesions or the growth of previous ones. At the same time, most patients had a very high tolerance and the relevant side effects such as fatigue (9% of cases) and anaemia (8%), were generally light”.
Moreover, the University Hospital of Navarra specialist highlighted, “in the analysis of the results for the patient subgroups, it was concluded that all the subgroups receiving the trial drug benefited thereof: both those who initially had a better functional state and those who had a worse one; those who had received one or two lines of chemotherapy (although those who had received treatment benefited more); those belonging to all age groups; those who had visceral affectation (hepatic or pulmonary metastasis) as well as those who did not, although the latter benefited more; and those who started with a high PSA as well as those who started with low levels thereof”.
New therapeutic paradigm for this kind of tumour
The results of this research, explained doctor Gil Bazo, “reinforces the new concept that patients with castration-resistant disease are not in fact resistant to hormonal treatment”.
In this vein he informs us that, “in recent years four new pharmaceutical drugs have been developed and hormonal treatment has gained importance, even after chemotherapy, which is cause for great hope for patients”.
For this reason, the model for tackling prostate cancer, the most common amongst men over 50, has changed. “When the tumour is detected at an early stage, radical treatment with surgery, radiotherapy or brachytherapy is carried out. From thereon, the illness can progress or not. When it was reproduced, it was considered that the disease was sensitive to hormonal treatment because the male hormones are the ones favourable to the growth of tumour cells”.
As he states, “in most patients the disease stops being sensitive to hormonal treatment within a year and a half to two years. Since 2004, the standard treatment in this situation is with docetaxel, a chemotherapeutic drug capable of controlling the illness in such circumstances”.
In fact, doctor Ignacio Gil Bazo recently took part as lead researcher from the University Hospital of Navarra in other multicentre clinical trials with the hormonal pharmaceutical drug enzalutamide. Given the results, plus those now obtained in the research with abiraterone acetate, the specialist in Oncology states that the therapeutic paradigm for castration-resistant disease tumours after receiving chemotherapy has changed: “It has meant the opening up of a second line of treatment. Although the first with hormones fails, this disease still has a hormonal component for the tumour cells to subsist. The fact of having received chemotherapy does not mean that dealing with hormones has no sense, but that now it regains importance”.
In any case, he specifies that the mechanism of the hormonal blockade of these new pharmaceutical drugs differs from the conventional: “It is not a pure antiandrogenic treatment, but a blockade of the synthesis of androgens in the adrenal glands. Abiraterone acetate is the first selective and irreversible inhibitor of CYP17 (enzyme that synthesises androgens in various locations of the organism) that has shown significant increase in survival within this clinical context”.
Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012 Oct;13(10):983-92.