Advanced Hormone-dependent Prostate Cancer Research Articles

Preliminary results of the "DUO" observational study: Quality of life assessment and cross-sectional follow-up of prostate cancer patients treated with degarelix.

62 Background: The use of androgen deprivation therapy (ADT), has increased over time in the treatment of prostate cancer (PCa). ATD is accompanied by side effects, some of which may increase the cardiovascular (CV) risk. The aim of this study was to evaluate the prevalence of cardiovascular risks and quality of life at the initiation of degarelix, a GnRH antagonist, and 6 months later, in patients with advanced hormone-sensitive PCa. Methods: The DUO study is a PASS, pharmaco-epidemiologic, longitudinal, multicenter observational study. It prospectively enrolled PCa patients during the first 6 months of treatment with degarelix. cohort to describe the prevalence of real-life cardiovascular co-morbidities in. The study was carried out in 46 French urology centers. At D0 and M6, the prevalence of CV, osteoporotic, metabolic, mood disorder, geriatric and sexual morbidity and risk factors were recorded using validated tools and questionnaires. EQ-5D questionnaire measured quality of life. The evolution of the disease (PSA levels) and the tolerance of the treatments were also reported. Results: A total of 124 patients with advanced hormone-dependent PCa (of whom 26.6% were metastatic) were included. At D0 57.7% of patients had a CV morbidity and CV risk factors. Metabolic co-morbidities were also present in 60.6% of patients, osteoporotic risk factors in 34%, sexual disorders in 58%, and mood disorders in 36%. ONCO-G8 score ≤ 14 was observed in 45.6% of patients aged ≥ 70 years. The percentage of patients with CV co-morbidities remained stable (56.7%). The rates of osteoporotic, metabolic, sexual, and mood-related morbidity and risk factors also remained unaltered. Likewise, quality of life remained stable between D0 and M6 (Scores: 0.765 and 0.813 respectively). At the same time, the median PSA rate decreased by -98.4% from D0 (p < 0.001). 42 adverse events (AEs) were reported in 22 patients: degarelix-related AEs were reported in 4.4% of patients. Conclusions: The results of the DUO study showed high prevalence of CV co-morbidity and risk factors in patients with advanced PCa. It also showed no significant increase in CV co-morbidities and risk-factors during the first 6 months of treatment with degarelix as it was observed for osteoporotic, metabolic, sexual, and mood-related disorders. The GnRH antagonist was well tolerated without major impact on quality of life. Assessment of multiple co-morbidities at the initiation and during ADT is mandatory for the optimal management of patients.

Patients and physician satisfaction of Degarelix in androgen deprivation therapy for advanced hormone-dependent prostate cancer in the Netherlands.

Background:To explore the effectiveness and safety of the gonadotropin-releasing hormone antagonist, Degarelix, for the treatment of advanced hormone-dependent prostate cancer (PCa) in a real-world setting.Methods:In this noninterventional study, patients with advanced hormone-dependent PCa were included. Primary endpoints were progression-free survival (PFS) failure defined as either prostate-specific antigen failure, additional therapy related to PCa, or death. Secondary endpoints included patient and physician satisfaction scores, urinary symptoms, and adverse events (AEs).Results:Of 274 patients with PCa, 271 received at least 1 dose of Degarelix. At a median follow-up of 12.2 (interquartile range 6.2–22.0) months, 148 patients (60.2%) had PFS failure. Thirty-five patients (13%) withdrew from the study due to AEs, 23 patients (8.4%) died, and 36 patients (13%) completed 3 years’ follow-up. Urinary symptoms significantly decreased over time. In the safety population, 87.8% of patients reported AEs, with injection-site reactions commonly reported. The majority of physicians and patients considered the therapy satisfactory and well tolerated.Conclusions:In this observational study, Degarelix treatment was well accepted by men with advanced hormone-dependent PCa. Compared with phase III studies, a higher proportion of patients had PFS failure, possibly due to the inclusion of men with more advanced disease in the current study, and more men reported AEs.

Switching from an LHRH Antagonist to an LHRH Agonist: A Case Report of 10 Finnish Patients with Advanced Prostate Cancer.

IntroductionLuteinizing hormone-releasing hormone (LHRH) analogues are widely used for the treatment of advanced hormone-dependent prostate cancer. However, there are currently no clinical guidelines for switching between LHRH analogues. It has been reported that there may be clinical benefits for patients switching between different formulations of LHRH agonists, as well as from an LHRH agonist to LHRH antagonist, but there are no published data on switching from an LHRH antagonist to an LHRH agonist. In this paper, we summarize the clinical notes of 10 patients with hormone-sensitive advanced prostate cancer who switched from an LHRH antagonist to an LHRH agonist.MethodsPatients with T3N0M0–T4N1M1 prostate cancer experiencing injection site reactions, such as pain and swelling, with monthly degarelix (Firmagon®) subcutaneous injections were switched to the 3-monthly leuprorelin acetate implant (Leuprorelin Sandoz®) subcutaneous injections.ResultsMean patient age was 75 years (SD 8.3; range 59–85) and Gleason scores ranged from 7 to 9. The mean [±standard deviation (SD)] duration of degarelix treatment was 5 ± 3.7 months (range 2–13). After switching, prostate serum antigen levels were comparable or reduced from those measured prior to switching, showing that efficacy was not compromised. Throughout the course of treatment, no patients reported injection site reactions. Patients reported increased satisfaction with the leuprorelin acetate implant versus degarelix, mainly because of a lack of injection site reactions and reduced frequency of injection.ConclusionThis is the first report of the clinical experience and potential cost implications of switching from an LHRH antagonist to an LHRH agonist. These data are consistent with other experiences of switching between LHRH analogues in terms of efficacy, safety, and potential cost savings, and provide preliminary evidence that the switch from an LHRH antagonist to an agonist is safe and equally efficacious.

Degarelix for Treating Advanced Hormone-Dependent Prostate Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its Single Technology Appraisal Process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of degarelix (Ferring Pharmaceuticals) to submit evidence for the clinical and cost effectiveness of degarelix for the treatment of advanced hormone-dependent prostate cancer. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE. The evidence, which included a randomised controlled trial (RCT) of degarelix versus leuprorelin, found that degarelix was non-inferior to leuprorelin for reduction of testosterone levels and that degarelix achieved a more rapid suppression of prostate-specific antigen levels and subsequently decreased incidences of testosterone flare associated with luteinising hormone releasing-hormone (LHRH) agonists. However, protection against testosterone flare for the comparators in the clinical trials was not employed in line with UK clinical practice. Further claims surrounding overall survival, cardiovascular adverse events and clinical equivalence of the comparator drugs from six RCTs of degarelix should be regarded with caution because of flaws and inconsistencies in the pooling of trial data to draw conclusions. The cost-effectiveness evidence included a de novo economic model. Based on the ERG's preferred base case, the deterministic incremental cost-effectiveness analysis (ICER) for degarelix versus 3-monthly triptorelin was £14,798 per quality-adjusted life-year (QALY) gained. Additional scenario analyses undertaken by the ERG resulted in ICERs for degarelix versus 3-monthly triptorelin ranging from £17,067 to £35,589 per QALY gained. Subgroup analyses undertaken using the Appraisal Committee's preferred assumptions suggested that degarelix was not cost effective for the subgroup with metastatic disease but could be cost effective for the subgroup with spinal metastases. The company submitted further evidence to NICE following an initial negative Appraisal Committee decision. Further analyses from the Decision Support Unit found that that, whilst some evidence indicated that degarelix could be cost effective for a small subgroup of people with spinal cord compression (SCC), data on the potential size of this subgroup and the rate of SCC were insufficient to estimate an ICER based on the evidence submitted by the company and a separately commissioned systematic review. NICE recommended degarelix as an option for treating advanced hormone-dependent prostate cancer in people with spinal metastases, only if the commissioner can achieve at least the same discounted drug cost as that available to the UK NHS in June 2016.

The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK.

PurposeComparing gonadotrophin-releasing hormone (GnRH) antagonists and agonists as androgen deprivation therapy for advanced prostate cancer (PC).MethodsThis article stems from a round-table meeting in December 2014 to compare the properties of GnRH agonists and antagonists in the published literature in order to identify the patient groups most likely to benefit from GnRH antagonist therapy. A broad PubMed and congress abstract search was carried out in preparation for the meeting to ensure that the latest data and opinion were available for the discussions.ResultsIn randomised, controlled trials, GnRH antagonist therapy provides more rapid suppression of luteinising hormone, follicle-stimulating hormone and testosterone than GnRH agonist treatment. Compared with the GnRH agonist, there is evidence of improved disease control by a GnRH antagonist, with longer interval to prostate-specific antigen progression and greater reduction of serum alkaline phosphatase. In a post hoc analysis of six randomised trials, the risk of cardiac events within 1 year of initiating therapy was significantly lower among men receiving GnRH antagonist than agonist. Pre-clinical laboratory data suggest a number of mechanisms whereby GnRH antagonist therapy may benefit men with pre-existing cardiovascular disease (CVD), the most plausible hypothesis being that, unlike GnRH agonists, GnRH antagonists do not activate T lymphocytes, which act to increase atherosclerotic plaque rupture.ConclusionWhen making treatment decisions, clinicians should consider comorbidities, particularly CVD, in addition to effects on PC. GnRH antagonists may be appropriate in patients with significant CV risk, existing osteopenia, lower urinary tract symptoms and significant metastatic disease.

Clinical and economic analysis of Degarelix (Firmagon) in treatment of patients with advanced hormone-dependent prostate cancer

Clinical and economic analysis of Degarelix (Firmagon) in treatment of patients with advanced hormone-dependent prostate cancer

Quality of Life Improvement in Patients Treated with Degarelix versus Leuprorelin for Advanced Prostate Cancer

We used responses to questionnaires included in the CS21 degarelix trial and published mapping algorithms to address the paucity of evidence for health related quality of life in patients with advanced hormone dependent prostate cancer treated with degarelix. We measured health related quality of life in 610 patients enrolled in the CS21 trial using SF-12® and EORTC QLQ-C30. Based on responses to these questionnaires we estimated patient utility using 4 published mapping algorithms. Utility was tested for relationships with aspects of the symptom and side effect burden that may be affected by degarelix treatment, that is prostate specific antigen progression and adverse events. Average utility in patients without prostate specific antigen progression or an adverse event was 0.742, similar to previously published utilities for nonprogressed prostate cancer states. Prostate specific antigen progression was associated with a utility decrement of between 0.062 and 0.134 depending on the mapping algorithm used. Of adverse events considered in our analysis musculoskeletal events were associated with the greatest effects on patient utility with a decrement of between 0.029 and 0.086. The 4 mapping algorithms generated similar utility estimates, although values derived from SF-12 were consistently lower than those derived from EORTC QLQ-C30. Prostate specific antigen progression status and the incidence of treatment and disease related adverse events result in significant decrements to patient health related quality of life. By slowing prostate specific antigen progression degarelix may improve patient utility and the health related quality of life burden.

A cost–utility analysis of degarelix in the treatment of advanced hormone-dependent prostate cancer in the United Kingdom

Objective:To determine the cost-effectiveness of the treatment of advanced hormone-dependent prostate cancer with degarelix compared to luteinizing hormone-releasing hormone (LHRH) agonists in the UK using the latest available evidence and the model submitted to AWMSG.Methods:A cost-effectiveness model was developed from the perspective of the UK National Health Service evaluating monthly injection of degarelix against 3-monthly leuprorelin therapy plus anti-androgen flare cover for the first-line treatment of patients with advanced (locally advanced or metastatic) hormone-dependent prostate cancer. A Markov process model was constructed using the patient population characteristics and efficacy information from the CS21 Phase III clinical trial and associated extension study (CS21A). The intention-to-treat (ITT) population and a high-risk sub-group with a PSA level >20 ng/mL were modeled.Results:In the base-case analysis using the patient access scheme (PAS) price, degarelix was dominant compared to leuprorelin with cost savings of £3633 in the ITT population and £4310 in the PSA > 20 ng/mL sub-group. The chance of being cost-effective was 95% in the ITT population and 96% in the PSA > 20 ng/mL sub-group at a threshold of £20,000 per quality-adjusted life-year (QALY). In addition, degarelix remained dominant when PSA progression was assumed equal and only the benefits of preventing testosterone flare were taken into account. Treatment with degarelix also remained dominant in both populations when the list price was used. The additional investment required to treat patients with degarelix could be offset in 19 months for the ITT population and 13 months for the PSA > 20 ng/mL population. The model was most sensitive to the hazard ratio assumed for PSA progression between degarelix and leuprorelin and the quality-of-life (utility) of patients receiving palliative care.Conclusion:Degarelix is likely to be cost-effective compared to leuprorelin plus anti-androgen flare cover in the first-line treatment of advanced hormone-dependent prostate cancer.

An update on the use of degarelix in the treatment of advanced hormone-dependent prostate cancer

Androgen deprivation therapy remains the mainstay of medical treatment for advanced prostate cancer. Commonly, this is achieved with medical androgen deprivation rather than surgical intervention as the permanence and psychological effects of the latter are unacceptable for most patients. Degarelix is a third generation antagonist of luteinizing hormone-releasing hormone (LHRH, also termed gonadotropin-releasing hormone) for the first-line treatment of androgen-dependent advanced prostate cancer. Degarelix acts directly on the pituitary receptors for LHRH, blocking the action of endogenous LHRH. The use of degarelix eliminates the initial undesirable surge in gonadotropin and testosterone levels, which is produced by agonists of LHRH. Degarelix is the most comprehensively studied and widely available LHRH antagonist worldwide. Clinical trials have demonstrated that degarelix has a long-term efficacy similar to the LHRH agonist leuprolide in achieving testosterone suppression in patients with prostate cancer. Degarelix, however, produces a faster suppression of testosterone and prostate-specific antigen (PSA), with no testosterone surges or microsurges, and thus prevents the risk of clinical flare in advanced disease. Recent clinical trials demonstrated that treatment with degarelix results in improved disease control when compared with an LHRH agonist in terms of superior PSA progression-free survival, suggesting that degarelix likely delays progression to castration-resistant disease and has a more significant impact on bone serum alkaline phosphatase and follicle-stimulating hormone. Degarelix is usually well tolerated, with limited toxicity and no evidence of systemic allergic reactions in clinical studies. Degarelix thus represents an important addition to the hormonal armamentarium for therapy of advanced androgen-dependent prostate cancer.

Two Innovative Pharmaceutical Forms of Leuprorelin: Results from 818 Patients with Advanced Prostate Cancer

This study set out to examine the efficacy and tolerability of two innovative implant forms of leuprorelin acetate in men with advanced hormone-dependent prostate cancer in everyday clinical practice. Data were collected from 818 patients (from 273 centers across Germany) who were pretreated with slow-release luteinizing hormone-releasing hormone (LHRH) agonist formulations and who were about to be switched to the leuprorelin implants. Patients received three injections of 1- or 3-month leuprorelin implant and physicians were asked to complete a case report form specific to each of the three clinic visits. Documented parameters included laboratory measurements, such as testosterone and prostate-specific antigen (PSA) levels, adverse events, and patient- and physician-rated assessments of the therapy. Compared with baseline, a significant decrease in both testosterone and PSA levels were measured after the first and second injections of leuprorelin implant. These results were confirmed for both the 1-month and 3-month implants in separate analyses. Switching, without treatment interruption, from Trenantone® (Takeda Pharma GmBH, Aachen, Germany) to the leuprorelin implant resulted in a significant decrease in the mean serum testosterone concentrations (P < 0.05) and a nonsignificant increase in the proportion of patients reaching castrate testosterone levels, while the number of patients with PSA values ≤ 4 ng/mL significantly increased (P = 0.045). Similar results were obtained for patients previously treated with goserelin who switched to leuprorelin implant. For 94% of patients, treating physicians rated the efficacy of leuprorelin implant as "very good" or "good." Treatment with leuprorelin implant was well tolerated, with only 61 adverse events reported in 42 (5.1%) patients. Patients and physicians rated the tolerability of leuprorelin implant as "very good" or "good" in 95% and 91% of cases, respectively. These results confirm the efficacy, tolerability, and ease of use of the leuprorelin implants among a large population of men with advanced, hormone-dependent prostate cancer treated in a clinical practice setting.

Clinical development of two innovative pharmaceutical forms of leuprorelin acetate

Two innovative pharmaceutical forms of leuprorelin acetate have been developed as 1-month and 3-month implants for the treatment of advanced hormone-dependent prostate cancer. These products contain active substance dispersed homogeneously in a biodegradable polymer. Here we present the key results from the clinical development of these slow-release implant formulations of leuprorelin. Two therapeutic studies of the 1-month implant were performed: a randomized, controlled study comparing the leuprorelin implant with leuprorelin prolonged-release microspheres (Enantone) as the active control; and a single-arm study of the leuprorelin implant. For the 3-month implant, four therapeutic studies were performed: a randomized, controlled study comparing the leuprorelin implant with leuprorelin prolonged-release microspheres (Trenantone) as the active control; a single-arm study of the leuprorelin implant; and two long-term studies with the 3-month implant administered twice, either 12 or 16 weeks apart. A pooled analysis of data from the comparator-controlled and single-arm studies of the 3-month implant was also conducted. The main inclusion criterion for all studies was histologically confirmed advanced prostate cancer, with primary endpoints based around successful testosterone suppression (≤0.5 ng/ml). In the comparator-controlled studies, both implants were as effective as the microspheres for achieving successful testosterone suppression and normalization of prostate-specific antigen (PSA) levels. Data from the single-arm and long-term studies were consistent with those from the comparator-controlled studies. In the pooled analysis, significantly more patients treated with the 3-month implant achieved successful testosterone suppression compared with the comparator (p ≤ 0.01). The safety profile of the implants in the comparator-controlled studies was similar to that of the prolonged-release microsphere formulation, and consistent with that of the luteinizing hormone-releasing hormone agonist class. The innovative 1-month and 3-month implants of leuprorelin acetate are at least as effective as leuprorelin acetate prolonged-release microspheres for achieving successful testosterone suppression and normalization of PSA in men with advanced hormone-dependent prostate cancer, with a comparable safety profile.

A new pharmaceutical form of leuprorelin acetate for the treatment of advanced prostate cancer: Clinical experience from a non-interventional study

Purpose: A new pharmaceutical form of leuprorelin acetate has been developed for the treatment of advanced prostate cancer. This product is a rod-shaped implant in which the active substance is dispersed homogeneously in a lactic acid polymer. The implant is administered once every 3 months by subcutaneous injection into the anterior abdominal wall, where it is hydrolytically degraded and the active substance is continually released. Here, we report data from a large noninterventional observational study of this implant conducted inGermany. Methods: Included patients were men diagnosed with advanced hormone-dependent prostate cancer and receiving, or about to start, treatment, with the 3-month implant. A total of 1148menwere analysed. The start of the observational period was the date of the first administration of the 3-month implant. Baseline demographic data and relevantmedical historywere collected at visit 1. Thepatients returned for two observational visits at 3-month intervals; additional injections could be given at these visits according to the clinical judgement of the treating physician. Themain objective of the study was to assess the safety profile of the 3-month implant in routine clinical practice. The incidence and frequency of the expected adverse drug reactions (ADRs) were assessed, and unexpected ADRs identified. At visits 2 and 3, physicians assessed treatment success and patients assessed the tolerability of the implant using a 5-point scale (very good, good, satisfactory, poor, and very poor). The efficacy of the medication was assessed from PSA measurements made during the routine medical examinations. Results: The mean age of the patients was 74.6 years and the mean duration of their prostate cancer was 22 months. Metastases were present in 242 patients. Overall, the type and incidence of ADRswere as expected for this product and the LHRH agonist class. Expected ADRs were experienced by 70.8% of patients, with hot flushes (554 patients; 48.3%) and increased sweating (383 patients; 33.4%) themost frequent. Other expected ADRs reported included loss of potency (33.2%), loss of libido (31.6%) and weight gain (25.5%). Only 15 patients (1.3%) experienced unexpected ADRs. In only 2 patientswere these considered to be drug-related; one patient experienced erysipelas and abdominal wall abscess after the second injection, and one patient experienced constipation and a slight decrease in haemoglobin after the first injection. Four patients died during the observation period; no death was considered to be related to study treatment. Physicians assessed treatment success as very good/good/satisfactory in more than 98% of patients at visit 2 and visit 3. More than 98% of patients assessed tolerability of the implant as very good/good/satisfactory at visit 2 and visit 3. Mean PSA decreased by more than 80% between visit 1 and visit 2, with a further slight decrease between visits 2 and 3. Conclusion: The new 3-month implant of leuprorelin acetate was well tolerated by patients. The type and incidence of ADRs were as expected for this product and the LHRH agonist class. PSA control was achieved in the majority of patients.

Degarelix: a guide to its use in advanced prostate cancer

Degarelix (Firmagon®), a gonadotropin-releasing hormone (GnRH) receptor antagonist, is indicated as an androgen-deprivation therapy in men with advanced hormone-dependent prostate cancer. It effectively induces and maintains suppression of serum testosterone to castration levels and has an acceptable tolerability profile. Relative to leuprolide, degarelix is associated with more rapid induction of testosterone and prostate-specific antigen (PSA) suppression without the testosterone surges associated with GnRH receptor agonists, and a potentially lower risk of the combined endpoint of PSA progression and death.

PCN100 A Cost–Utility Analysis of Degarelix in the Treatment of Advanced Hormone-Dependent Prostate Cancer in Scotland

PCN100 A Cost–Utility Analysis of Degarelix in the Treatment of Advanced Hormone-Dependent Prostate Cancer in Scotland

A 6-month depot formulation of leuprolide acetate is safe and effective in daily clinical practice: a non-interventional prospective study in 1273 patients

BackgroundTestosterone stimulates growth in many prostate tumours. The established GnRH analogue leuprolide acetate is incorporated in a novel biodegradable polymer matrix (Atrigel® delivery system), that can be administered to reduce testosterone levels in men with advanced hormone-dependent prostate cancer. This novel formulation is available as a 1-, 3- and most recently 6-month depot (Eligard® 45 mg). The latter was shown to lower and maintain safe and effective serum testosterone suppression in a clinical study.MethodsA non-interventional study to confirm the efficacy and safety of 6-monthly leuprolide acetate (Eligard® 45 mg) in routine urological practice was performed in Germany. Data were obtained from 1273 patients under the care of 634 urologists, and were analysed descriptively. Concentrations of PSA and serum testosterone were documented at the baseline visit and at 6 and 12 months following 6-monthly leuprolide acetate. The participating physicians were also asked to assess the efficacy, tolerabilty and handling of 6-monthly leuprolide acetate.ResultsSerum concentrations of PSA and testosterone were decreased substantially within 6 months of initial 6-monthly leuprolide acetate administration. At 12 months, median reductions of 96% (to 0.5 ng/ml) in PSA, and 90% (to 8.9 ng/dl) in serum testosterone, were observed. Further PSA and serum testosterone decreases were also observed in a subpopulation of patients who switched to 6-monthly leuprolide acetate from other GnRH analogues. Physicians rated 6-monthly leuprolide acetate as easy to use, and patients reported good tolerability. Adverse events occurred in 9% of patients; the majority were not serious. In particular, low rates of hot flushes were reported.ConclusionsThis non-interventional study showed that the reliable reduction of PSA and testosterone levels demonstrated in previous clinical studies of twice-yearly leuprolide acetate can also be achieved in routine clinical practice. This study also confirmed good tolerability of 6-monthly leuprolide acetate in routine clinical use and received positive appraisal from physicians.

Ozarelix, a fourth generation GnRH antagonist, induces apoptosis in hormone refractory androgen receptor negative prostate cancer cells modulating expression and activity of death receptors

Antagonistic or agonistic analogues of gonadotropin-releasing hormone are extensively used for the treatment of advanced hormone-dependent prostate cancer. However, the majority of recurrent prostate tumors is androgen independent. This study explored the in vitro effects on DU145 and PC3 cell lines, two models of androgen-independent prostate cancer, of a fourth generation GnRH antagonist (Ozarelix). Ozarelix was added to cultures and toxicity, cell cycle modifications, cell viability and caspase activity were investigated. Ozarelix showed antiproliferative effects and produced an accumulation of cells in G2/M cell cycle phase. Apoptosis was related with caspase-8-dependent caspase 3 activation with down-regulation of c-FLIP (L) and a sensitization to TRAIL-induced apoptosis linked also to increased expression and activity of death receptors DR4/5 and Fas. TRAIL-resistant cancer cells can be sensitized to TRAIL by Ozarelix. This effect may be achieved by the activation of apoptotic pathway improving the therapeutic effects in androgen independent tumor cell lines. However, a better understanding of molecular mechanisms by which GnRH antagonists may act in androgen independent models is necessary.

News &amp; Notes

AbstractPCTs limit HPV vaccine to national programmeAs many as half of PCTs may be pressuring GPs to limit prescribing of the HPV vaccine to those patients covered by the national immunisation programme, according to reports in the newspaper GP.The programme is funded centrally, but PCTs pay for additional prescribing of the vaccine. A full course of Cervarix or Gardasil costs £241.50.The newspaper's survey of 101 GPs revealed that one‐third of respondents were prescribing outside the immunisation programme; a majority considered that vaccination is appropriate for a patient not yet sexually active who requests it.Survival with non‐hormonal treatments for breast cancerImprovements in chemotherapy have resulted in major gains in survival for patients with advanced breast cancer, according to an exhaustive meta‐analysis of 148 comparative randomised trials (J Natl Cancer Inst 2008; 100: 1780‐91).Compared with monotherapy with non‐anthracyclines, regimens containing an anthracycline reduced mortality by 22–33 per cent. Treatment with a taxane, alone or with an anthracycline, was similarly effective. Combining a taxane with gemcitabine or capecitabine approximately halved the risk of death.Overall, whereas older agents offered increased survival of around one year, these data suggest that newer treatments offer a further 4.2–12.5 months.Degarelix approved in EuropeGnRH receptor antagonist degarelix has received European approval for treatment of advanced hormone dependent prostate cancer. Ferring Pharmaceuticals says degarelix suppresses testosterone levels to below 0.5ng/ml in 96 per cent of patients within 3 days, and in all patients after 14 days, compared with 18 per cent with leuprorelin. This was associated with a median decline in PSA levels of 64 per cent compared with 18 per cent with leuprorelin. The adverse effect profiles were similar.Fertility drugs raise cancer riskIsraeli investigators have published new evidence that treatment to induce ovulation may increase risk of cancer (Am J Epidemiol 2008; published online doi:10.1093/aje/kwn318).Their cohort study identified 15030 women in Jerusalem who gave birth between 1974 and 1976. Among the 567 who used drugs to induce ovulation, overall risk of cancer was increased by 36 per cent compared with controls. Risk of uterine cancer was increased more than fourfold by clomiphene. Risks of malignant melanoma and non‐Hodgkin's lymphoma were also raised; a 40 per cent increased risk of breast cancer was of borderline statistical significance. Risk of ovarian cancer was not increased. The findings are based on relatively few cases, but are supported by evidence of a dose‐response relationship: women who took longer to conceive were at higher risk.Radiotherapy enhances endocrine therapy in prostate cancerCombining radiotherapy with endocrine therapy reduces mortality in men with locally advanced prostate cancer, a Scandinavian study suggests (Lancet 2008; published online doi:10.1016/S0140‐6736(08)61815‐2).After a median follow‐up of 7.6 years in 875 men, the cumulative 10‐year incidence of prostate‐cancer specific death was 24 per cent with endocrine therapy alone and 12 per cent with endocrine therapy plus radiotherapy – a relative risk of 0.44. Overall mortality was 39 and 30 per cent respectively. PSA recurrence was less frequent with radiotherapy (26 vs 75 per cent), but adverse urinary, rectal and sexual effects were more common. Copyright © 2009 Wiley Interface Ltd

Effectiveness and tolerance of 1 dosage forms (subcutaneous and intramuscular) of decapeptyl depot in patients with advanced prostate carcinoma

The intramuscular (i.m.) administration of Decapeptyl Depot has been approved in Germany for the treatment of advanced hormone dependent prostate cancer since July 1990. In this study a reformulated Decapeptyl Depot, administered as a first-line endocrine therapy, was injected intramuscularly (i.m.) or subcutaneously (s.c.) every 28 days for 6 months. At 12 different hospitals, 52 prostate cancer patients were treated, whereby 25 patients received a s.c. injection and 27 patients a i.m. injection. Testosterone was measured as the main parameter: after 28 days, both the s.c. and the i.m. application form of Decapeptyl Depot successfully reduced initial testosterone levels of at least 2.3 ng/ml to steady-state castration levels below 1.2 ng/ml, maintaining this complete suppression for the entire length of the trial (168 days). Decapeptyl Depot was well tolerated and very acceptable to the patients in both groups. Side effects were few and predictable, being largely associated with decreased testosterone concentrations. No cumulation in triptorelin serum levels was observed within the 6 months of treatment. Decapeptyl Depot, administered subcutaneously or intramuscularly was effective and safe in the treatment of patients with advanced prostate cancer.