New Treatment Options For Patients With Prostate Cancer

A Dutch study suggested treating prostate cancer patients with higher doses of radiotherapy significantly improved patient outcome and treatment over a five-year period. Another evaluated which patients would benefit from early adjuvant anti-androgen therapy. Data was presented on a new compound to treat androgen independent prostate cancer. An Australasian study reviewed the benefits of administering maximal androgen deprivation treatment before radiotherapy.

The Dutch study, a multicentre randomised Phase III trial, recruited 669 patients with stage T1b-T4N0M0 (free from cancer in the lymph nodes and no metastasis has occurred) prostate cancer and with baseline characteristics of median PSA (prostate specific antigen) of 13.0ng/ml. 63% of patients had T1-2 tumours (smaller tumours localised to the prostate). Patients were divided into three prognostic groups of low, intermediate and high risk which included 18%, 27% and 55% of patients respectively. These groups were treated with either the higher dose of radiotherapy at 78Gy or the conventional dose at 68Gy. Some of the patients from the intermediate and high risk groups were also receiving hormonal therapy (143 in total).

The aim of the study was to determine whether the higher dose of radiotherapy, 78Gy, offered more effective treatment of prostate cancer than the conventional dose at 68Gy. The study's endpoint was defined as 'freedom from failure' or clinical failure (clinical relapse or start of hormone treatment).

Results indicated at five years, that 'freedom from failure' was significantly improved in patients receiving the 78Gy radiotherapy dose than those receiving the 68Gy dose. The intermediate risk patients experienced the most benefit from the higher dose treatment (74% vs 58%. p=0.03). The gain in the high risk group was smaller (52% vs 44%, p=0.1) and there was no benefit in the low risk group (84% vs 86%, p=0.7). In overall data terms, there were no significant differences in overall survival (83% vs 82%) and 'freedom from clinical failure' (76% vs 76%) between the two radiotherapy doses.

Speaking on behalf of the study authors at the Netherlands Cancer Institute in Amsterdam, Professor Harry Bartelink commented, "This trial demonstrated that for radiotherapy of prostate cancer patients, higher radiation doses are more effective than conventional doses, and that these doses can be delivered safely. The consequence of this first analysis trial is that the standard treatment for prostate cancer should change to a higher radiation dose, as we predict that a higher local control rate will be obtained and eventually, a higher survival rate."

In the largest hormone therapy trial, the Early Prostate Cancer programme (EPC), ever conducted in prostate cancer patients, results indicated which patients would benefit from early anti-androgen therapy over a period of seven years. Patients (8113 in total) selected were diagnosed with localised (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N+) prostate cancer (all M0). Patients received bicalutamide (anti-androgen) or placebo once daily plus standard care (radiotherapy, radical prostatectomy surgery or watchful waiting -- see if tumour progresses or stays the same without treatment). Primary endpoints were overall survival (OS) and objective progression-free survival (PFS).

The data revealed that in localised disease, there was no significant PFS or OS benefit but in locally advanced disease, bicalutamide significantly improved OS in patients in combination with radiotherapy. Additionally bicalutamide produced a trend towards improved OS in patients with locally advanced disease who would have otherwise undergone 'watchful waiting'. However no overall survival benefit was achieved in patients who had surgery - radical prostatectomy.

Speaking about his study findings, Professor Peter Iversen stated, "Results from the EPC Trial Programme provide a significant step forward in our understanding of which men with early non metastatic prostate cancer benefit from the addition of bicalutamide 150mg therapy, enabling physicians to be more targeted in their selection of appropriate treatments. These data show that men with localised disease gain no significant benefit while men with locally advanced disease derive significant benefit from addition of bicalutamide therapy."

In an ongoing study, a new immunotherapy product, APC8015, is currently under investigation for the treatment of non-hormone responsive or androgen independent prostate cancer (AIPC). Preliminary results have been released from one of the two Phase III trials which demonstrated a significant survival for APC8015 treated patients in the intent-to-treat group compared with placebo. Results from the other clinical trial will be reported later and may confirm and strengthen the data found from the first trial.

Study author, Dr Tia Higano from The University of Washington, USA commented, "The combined data from these trials of APC8015 versus placebo suggest that immunotherapy might impact survival in men with androgen independent prostate cancer. APC8015 has a favorable safety profile. Future studies in patients with earlier stage disease or in combination with other agents will be of great interest."

The Australasian study determined whether 3 or 6 months maximal androgen deprivation (MAD) administered prior to and during radiotherapy improved treatment outcomes for patients with locally advanced prostate cancer. 818 patients, between June 1996 and February 2000, were randomised at 19 Australian and New Zealand centres to receive radiotherapy alone or MAD treatment either starting at 3 or 6 months before radiotherapy. Their cancers were staged at T2bc, T3 and T4 (N0, M0).

Improvements in various outcome measures were observed with 3 months MAD treatment prior to radiotherapy; in reduced local failure, improved biochemical failure free survival, clinical disease free survival and freedom from salvage therapy. The 6 month MAD treatment prior to radiotherapy improved on these effects and also reduced distant failure and produced significant improvement in cause specific survival. The investigators added that patients with 'high risk' cancer also experienced a strong trend towards improved overall survival. They concluded that further follow up studies were needed to estimate the size of survival benefits precisely.

About Prostate Cancer

The prostate is a small gland about the size and shape of a walnut situated just below the bladder and surrounding the urethra. The prostate produces the seminal fluid in which sperm is transported. Prostate cancer begins with small changes in size and shape of the prostate gland cells which can develop into an uncontrolled growth of cells.

Prostate cancer predominantly affects Western populations although the black population has a significantly higher rate than the white population. The lowest incidence is seen in Asian populations.1There are just under 238,000 cases of prostate cancer in Europe each year and it is the cause of 85,000 deaths annually. 2

Risk factors associated with prostate cancer include family history of the disease, age (predominantly men over 50 years of age) and a diet high in red meat and dairy products. 3

Once the cancer has been diagnosed it is graded and staged to assess aggressiveness of the tumour and how far it has spread, and for evaluating the type of treatment required. Treatment can involve surgery, radiotherapy, hormone treatments and chemotherapy (advanced cases). 3 Prostate cancer diagnosed at an early stage is usually treated by a combination of surgery and radiotherapy; more advanced cases are treated with radiotherapy and hormone therapies such as the anti-androgens. In patients with metastatic disease where the cancer has spread to other parts of the body, a multi-disciplinary approach which could include chemotherapy, is implicated.