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Peter Iversen

Publications and source records attributed to Peter Iversen.

At least 19 recordsLinked to original sources
PubMed2007

[Prostate cancer in Denmark 1943-2002].

INTRODUCTION: Previous studies in Denmark have reported an increase in prostate cancer (PC) incidence- and mortality rates. So far, it has not been possible to establish the rising incidence as a consequence of an increase in diagnostic procedures. This study reviews the trends in PC incidence and mortality rates in Denmark during the 60-year-period from 1943 to 2002. MATERIAL AND METHODS: Register-based study. RESULTS: The age-standardised (World Standard Population) rate of PC in Denmark increased from 11.4/100,00 in the period 1943-47 to 38.2/100,000 in the period 1998-2002. Mortality rate increased from 13.5/100,000 in 1953 to 19.1/100,000 in the period 1993-98. Within the last 10 years changes in age-distribution and clinical stage, especially among younger patients, indicate a shift towards a more active diagnostic policy. CONCLUSION: In concordance with other studies we found an increasing PC incidence. In the last 10-year-period studied from 1993 to 2002, our study found the rise in incidence most likely explained by an increase in diagnostic activity, presumably as unsystematic PSA-based "gray-zone screening". This development contrasts with the national recommendation for PSA-based screening for PC. The rising incidence will necessitate allocation of increased resources for evaluation, treatment, and follow-up of patients with PC.

Aged↗
PubMed2006

Tolerability, efficacy and pharmacokinetics of bicalutamide 300 mg, 450 mg or 600 mg as monotherapy for patients with locally advanced or metastatic prostate cancer, compared with castration.

OBJECTIVE: To evaluate the pharmacokinetics, tolerability and effect on endocrinology of bicalutamide given as once-daily monotherapy at doses of >150 mg to patients with locally advanced (M0) or metastatic (M1) prostate cancer, with efficacy as a secondary endpoint. PATIENTS AND METHODS: Patients were initially enrolled to receive bicalutamide 300 mg in a non-randomized phase, after which further patients were randomized to higher bicalutamide doses (in 150 mg increments) or castration. Overall, 248 patients received bicalutamide at 300 mg (21), 450 mg (95) or 600 mg (42), or castration (90). RESULTS: Systemic exposure to bicalutamide stabilised at a dose of approximately 300 mg, as determined by pharmacokinetic analysis. The tolerability of high doses of bicalutamide was similar to that of the 150 mg dose, with no increase in the incidence of adverse events. Patients receiving bicalutamide had early increases in the mean levels of oestradiol, testosterone and luteinizing hormone, which were maintained throughout the study. Levels of these hormones rapidly decreased in the castration group and remained low. From baseline (first day of treatment) to 12 weeks there was an equivalent reduction in prostate-specific antigen (PSA) levels across all four groups. At a median follow-up of 5 years, there was no significant survival difference between patients who received bicalutamide and those who received castration, either in M0 or M1 disease. CONCLUSION: The low median PSA level (180 ng/mL) of patients with M1 disease might account for the lack of survival difference between the treatment groups. Further studies are needed to assess whether high-dose bicalutamide monotherapy can provide equivalent efficacy to castration in patients with M1 prostate cancer.

Aged↗
PubMed2006

Distribution of PK11195 binding sites in porcine brain studied by autoradiography in vitro and by positron emission tomography.

The cerebral distribution of peripheral-type benzodiazepine binding sites (PBBS) in human brain has been investigated by positron emission tomography (PET) with the specific radioligand [11C]PK11195 in diverse neuropathological conditions. However, little is known about the pattern of PK11195 binding sites in healthy brain. Therefore, we used quantitative autoradiography to measure the saturation binding parameters for [3H]PK11195 in cryostat sections from young Landrace pigs. Specific binding was lowest in the cerebellar white matter (85 fmol mg(-1)) and highest in the caudate nucleus (370 fmol mg(-1)), superior colliculus (400 fmol mg(-1)), and anterior thalamic nucleus (588 fmol mg(-1)). The apparent affinity was in the range of 2-6 nM in vitro, predicting high specific binding in PET studies of living brain. However, the distribution volume (V(d), ml g(-1)) of high specific activity [11C]PK11195 was nearly homogeneous (3 ml g(-1)) throughout brain of healthy Landrace pigs, and was nearly identical in studies with lower specific activity, suggesting that factors in vivo disfavor the detection of PBBS in Landrace pigs with this radioligand. In young, adult Göttingen minipig brain, the magnitude of V(d) for [11C]PK11195 was in the range 5-10 ml g(-1), and had a heterogeneous distribution resembling the in vitro findings in Landrace pigs. There was a trend toward globally increased V(d) in a group of minipigs with acute MPTP-induced parkinsonism, but no increase in V(d) was evident in the same pigs rescanned at 2 weeks after grafting of fetal mesencephalon to the partially denervated striatum. Thus, [11C]PK11195 binding was not highly sensitive to constituitively expressed PBBS in brain of young Landrace pigs, and did not clearly demonstrate the expected microglial activation in the MPTP/xenograft model of minipigs.

Animals↗
PubMed2006

Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma.

BACKGROUND: To examine the prognostic value of markers of bone metabolism (serum PINP, BAP, and CTX-I) and serum YKL-40 in metastatic prostate carcinoma (PC). METHODS: The biomarkers were determined by ELISAs in 153 metastatic PC patients before treatment with parenteral estrogen or total androgen ablation. The median follow-up was 4.9 years. One hundred fifteen patients died. RESULTS: The biomarkers were increased in the patients compared to controls (P < 0.001), and related to performance status and Soloway score (except YKL-40), but not to T-category and WHO tumor grade. PINP was elevated in 87%, BAP (55%), CTX-I (33%), and YKL-40 (43%). Univariate analysis showed an association to survival: PINP (HR = 1.6, P < 0.0001), BAP (HR = 1.4, P < 0.0001), CTX-I (HR = 1.7, P < 0.0001), and YKL-40 (HR = 1.4, P = 0.004). In multivariate Cox analysis performance status, WHO grade, Soloway score, PINP, and YKL-40 were independently predictive factors. CONCLUSIONS: High serum PINP, BAP, CTX-I, and YKL-40 are associated with poor outcome of metastatic PC patients.

Adipokines↗
PubMed2006

Peripheral benzodiazepine receptors in the brain of cirrhosis patients with manifest hepatic encephalopathy.

PURPOSE: It has been suggested that ammonia-induced enhancement of peripheral benzodiazepine receptors (PBRs) in the brain is involved in the development of hepatic encephalopathy (HE). This hypothesis is based on animal experiments and studies of post-mortem human brains using radiolabelled PK11195, a specific ligand for PBR, but to our knowledge has not been tested in living patients. The aim of the present study was to test this hypothesis by measuring the number of cerebral PBRs in specific brain regions in cirrhotic patients with an acute episode of clinically manifest HE and healthy subjects using dynamic (11)C-PK11195 brain PET. METHODS: Eight cirrhotic patients with an acute episode of clinically manifest HE (mean arterial ammonia 81 micromol/l) and five healthy subjects (22 micromol/l) underwent dynamic (11)C-PK11195 and (15)O-H(2)O PET, co-registered with MR images. Brain regions (putamen, cerebellum, cortex and thalamus) were delineated on co-registered (15)O-H(2) (15)O and MR images and copied to the dynamic (15)O-H(2)O and (11)C-PK11195 images. Regional cerebral blood flow (CBF) ((15)O-H(2)O scan) and the volume of distribution of PK11195 ((11)C-PK11195 scan) were calculated by kinetic analysis. RESULTS: There were regional differences in the CBF, with lowest values in the cortex and highest values in the putamen in both groups of subjects (p<0.05), but no significant differences between the groups. There were no significant differences in the volume of distribution of PK11195 (V (d)) between regions or between the two groups of subjects. Mean values of V (d) ranged from 1.0 to 1.1 in both groups of subjects. CONCLUSION: The results do not confirm the hypothesis of an increased number of PBRs in patients with HE.

Adult↗
PubMed2006

Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer: updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years.

OBJECTIVE: The Early Prostate Cancer (EPC) programme is evaluating the efficacy and tolerability of bicalutamide following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N + ) non-metastatic prostate cancer. Herein we report the latest findings after a median follow-up period of 7.1 years from the Scandinavian Prostate Cancer Group (SPCG)-6 study, one of three trials in the EPC programme. MATERIAL AND METHODS: A total of 1218 patients were randomized on a 1:1 basis to either bicalutamide 150 mg/day (n=607) or placebo (n=611) following standard care; 81.4% were followed conservatively (watchful waiting). The primary endpoints were objective progression-free survival (PFS) and overall survival (OS). RESULTS: In patients with localized disease there was no significant difference in PFS [hazard ratio (HR) 0.85; 95% CI 0.69-1.06; p=0.15] and a trend towards decreased OS with bicalutamide plus standard care compared with standard care alone (HR 1.23; 95% CI 0.96-1.58; p=0.11). In patients with locally advanced disease, bicalutamide significantly improved PFS, reducing the risk of progression by 53% compared with standard care alone (HR 0.47; 95% CI 0.37-0.59; p<0.001). The median time to progression was 8.8 years for bicalutamide plus standard care and 7.1 years for standard care alone. There was a significant improvement in OS with bicalutamide plus standard care, with a reduction in the risk of death of 35% versus standard care alone (HR 0.65; 95% CI 0.50-0.85; p=0.001). CONCLUSION: This analysis of the SPCG-6 study showed that bicalutamide plus standard care offers significant PFS and OS benefits for patients with locally advanced disease, but not for those with localized disease.

Aged↗
PubMed2006

Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer.

OBJECTIVE: To evaluate, in the ongoing Early Prostate Cancer (EPC) trial programme, the efficacy and tolerability of bicalutamide 150 mg once daily in addition to standard care for localized or locally advanced, nonmetastatic prostate cancer. PATIENTS AND METHODS: The EPC programme comprises three randomized, double-blind, placebo-controlled trials designed for combined analysis. Following standard care, 8113 men with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N+) prostate cancer (all M0) received oral bicalutamide 150 mg once daily or oral placebo. The primary endpoints were progression-free survival (PFS) and overall survival. RESULTS: The large EPC trial programme is defining men who benefit or do not from early or adjuvant antiandrogen therapy. At a median follow-up of 7.4 years, in localized disease there is no benefit to PFS by adding bicalutamide to standard care, and there is a trend (hazard ratio, HR, 1.16; 95% confidence intervals, CI, 0.99-1.37; P = 0.07) towards decreased survival in patients otherwise undergoing watchful waiting. However, in locally advanced disease, bicalutamide significantly improved PFS irrespective of standard care. Bicalutamide significantly improved overall survival in patients receiving radiotherapy (HR 0.65; 95% CI 0.44-0.95; P = 0.03); this was driven by a lower risk of prostate cancer-related deaths. Bicalutamide produced a trend towards improved overall survival in patients with locally advanced disease otherwise undergoing watchful waiting (HR 0.81; 95% CI 0.66-1.01; P = 0.06). No survival difference was evident in the prostatectomy subgroup. CONCLUSIONS: This ongoing programme is clarifying the role of early or adjuvant antiandrogen therapy in prostate cancer. Patients with localized disease do not appear to derive clinical benefit from added bicalutamide. However, adding bicalutamide 150 mg to standard care provides significant clinical benefits in patients with locally advanced prostate cancer, irrespective of primary therapy.

Aged↗
PubMed2005

Expression of urokinase plasminogen activator, its receptor and type-1 inhibitor in malignant and benign prostate tissue.

The plasminogen activation (PA) cascade participates in degradation of extracellular matrix during cancer invasion. We have studied the expression of urokinase-type plasminogen activator (uPA) mRNA, uPA receptor (uPAR) mRNA and immunoreactivity, and type-1 plasminogen activator inhibitor (PAI-1) mRNA and immunoreactivity in 16 prostate adenocarcinomas and 9 benign prostate hyperplasias. uPA mRNA and uPAR mRNA expression were found in 9 and 8 of the adenocarcinomas, respectively, and in 7 and 6 of the benign hyperplasias, respectively. In both malignant and benign lesions, expression of these 2 mRNAs was predominantly seen in cells identified as macrophages, which in most of the carcinomas (approximately 90%) were located in the interstitial tissue between the tumor cell islands, while in most of the benign hyperplasias they were located in the lumen of the glands and were in only a few cases (approximately 30%) found in the interstitial tissue. uPAR immunoreactivity correlated with the mRNA expression and was, in addition, found in neutrophils. PAI-1 mRNA was detected in 13 of the 16 carcinomas and in 8 of the 9 benign hyperplasias, located in scattered fibroblast-like cells in both groups, in some vascular structures and in a few macrophages located in the interstitial tissue of both malignant and benign lesions. A similar expression pattern was found for PAI-1 immunoreactivity. In 8 of the 16 carcinomas, all 3 components were present, and in several areas colocalization was observed in stromal cells in close proximity to cancer cell islands. No immunoreactivity and/or mRNA expression of uPA, uPAR or PAI-1 was observed in cancer cells or in other epithelial cells in any of the cases.

Adenocarcinoma↗
PubMed2005

Bicalutamide ('Casodex') 150 mg as adjuvant to radiotherapy in patients with localised or locally advanced prostate cancer: results from the randomised Early Prostate Cancer Programme.

BACKGROUND AND PURPOSE: The ongoing Early Prostate Cancer (EPC) programme is assessing bicalutamide ('Casodex') 150 mg, either alone or as adjuvant to treatment of curative intent, in patients with localised or locally advanced prostate cancer (n=8113). This paper presents an exploratory analysis of the subgroup of the EPC programme who received radiotherapy with curative intent (n=1370) in order to determine the efficacy (in terms of progression-free survival [PFS]) and tolerability of bicalutamide 150 mg in this setting. PATIENTS AND METHODS: 1370 patients with T1-4, MO, any N prostate cancer received bicalutamide 150 mg or placebo adjuvant to radiotherapy of curative intent. This analysis was undertaken at median 5.3 years' follow-up. RESULTS: In patients with locally advanced disease (n=305), bicalutamide adjuvant to radiotherapy significantly increased PFS by 53% (event-time ratio 1.53; 95% confidence intervals [CI] 1.16, 2.02) compared with placebo and reduced the risk of disease progression by 42% (hazard ration [HR] 0.58; 95% CI 0.41, 0.84; P=0.00348). In these patients, objective progression was experienced by 33.5% of those randomised to bicalutamide versus 48.6% for those randomised to placebo. The between-group difference in patients with localised disease (n=1065) failed to reach statistical significance (HR 0.80; 95% CI 0.62, 1.03; P=0.088). The most common adverse events were breast pain (74.8%) and gynaecomastia (66.6%), which were mild to moderate in >90% of cases. CONCLUSIONS: Bicalutamide 150 mg/day given as adjuvant to radiotherapy significantly improved PFS in patients with locally advanced prostate cancer. For patients with localised disease, the results at this stage from the radiotherapy subgroup and the overall EPC programme suggest that adjuvant hormonal therapy is currently not appropriate. There were no unexpected tolerability findings.

Aged↗
PubMed2005

Inguinal hernia in stage M0 prostate cancer: a comparison of incidence in men treated with and without radical retropubic prostatectomy--an analysis of 1105 patients.

OBJECTIVES: To analyze the incidence of inguinal hernia (IH) in a large group of patients with nonmetastatic prostate cancer who were treated nonoperatively, and to compare it with the incidence in a subset of patients who had undergone radical retropubic prostatectomy (RRP). IH has been reported in 12% to 21% of men at a mean period of 6 to 10 months after RRP. However, whether IH truly represents a complication after RRP has been somewhat debatable owing to the lack of proper control groups. METHODS: A total of 953 patients treated without surgery (nonoperative group) and 152 patients who underwent RRP (operative group) were selected from the Scandinavian Prostate Cancer Group Study No. 6 database consisting of 1218 patients with nonmetastatic prostate cancer. Radiotherapy, cryotherapy, and a follow-up duration of less than 3 months were exclusion criteria. Patients were followed up for any new medical condition at 12-week intervals for a mean period of 39 months (nonoperative group) and 50 months (operative group). RESULTS: Of the 953 patients in the nonoperative group, 23 (2.4%) developed IH versus 13 (8.6%) of 152 in the operative group (log-rank [Mantel-Cox] P = 0.010). CONCLUSIONS: Within comparable age groups, the incidence of IH in men with prostate cancer treated without surgery was significantly lower than that after RRP. This phenomenon seems to be causally related to the surgical procedure. The increased risk of IH after RRP deserves further recognition and should be included in the preoperative information given to patients. Studies are warranted to define the causal mechanisms, as well as possible preventive measures.

Aged↗
PubMed2004

Is the efficacy of hormonal therapy affected by lymph node status? data from the bicalutamide (Casodex) Early Prostate Cancer program.

OBJECTIVES: To report an exploratory subgroup analysis assessing the extent to which the overall benefit found in the Early Prostate Cancer program is dependent on lymph node status at randomization. The program is ongoing, and the overall survival data are immature. The first combined analysis of the bicalutamide (Casodex) Early Prostate Cancer program at 3 years' median follow-up showed that bicalutamide, 150 mg once daily, plus standard care (radical prostatectomy, radiotherapy, or watchful waiting), significantly reduced the risk of objective progression and prostate-specific antigen (PSA) doubling in patients with localized/locally advanced prostate cancer. METHODS: Men (n = 8113) with localized/locally advanced disease received bicalutamide 150 mg or placebo once daily, plus standard care. The time to event data (objective progression, PSA doubling) was analyzed by lymph node status at randomization. RESULTS: Compared with standard care alone, bicalutamide significantly reduced the risk of objective progression, irrespective of lymph node status, with the most pronounced reduction in patients with N+ (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.15 to 0.56) compared with those with N0 (HR 0.59; 95% CI 0.48 to 0.73) and Nx (HR 0.60; 95% CI 0.50 to 0.72) disease. The largest decrease in risk of PSA doubling with bicalutamide was observed in N+ disease (HR 0.16; 95% CI 0.09 to 0.29), with significantly reduced risks seen in N0 (HR 0.45; 95% CI 0.40 to 0.51) and Nx (HR 0.38; 95% CI 0.33 to 0.44) disease. CONCLUSIONS: The greatest reduction in the risk of objective progression and PSA doubling with bicalutamide was seen in patients with N+ disease. However, bicalutamide also provided a statistically significant benefit in those with N0 and Nx disease.

Adult↗
PubMed2004

Chemotherapeutic prevention studies of prostate cancer.

PURPOSE: Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, ie the administration of agents that inhibit 1 or more steps in the natural history of prostate carcinogenesis. We review prostate cancer chemoprevention studies in Europe. MATERIALS AND METHODS: Published studies were identified in a search of MEDLINE. Information about ongoing studies was provided by author access to protocols. RESULTS: A variety of chemoprevention studies have focused on the role of dietary factors, vitamins and trace elements in prostate cancer. Some of these studies have been prospective, randomized and double-blinded, while others have used retrospective or epidemiological approaches. Large scale randomized studies are also evaluating the role of 5alpha-reductase inhibitors, which inhibit the conversion of testosterone to the more potent androgen dihydrotestosterone. CONCLUSIONS: Robust evidence is lacking for the value of chemopreventive agents in prostate cancer. Current evidence does suggest that vitamin E and selenium may have a role in prostate cancer chemoprevention. Data from 2 studies, 1 examining the type 1 5alpha-reductase selective inhibitor finasteride and the other using the dual 5alpha-reductase inhibitor dutasteride, will determine the benefits of androgen inhibition strategies for prostate cancer chemoprevention.

Anticarcinogenic Agents↗
PubMed2004

Bicalutamide (150 mg) versus placebo as immediate therapy alone or as adjuvant to therapy with curative intent for early nonmetastatic prostate cancer: 5.3-year median followup from the Scandinavian Prostate Cancer Group Study Number 6.

PURPOSE: We evaluated the benefits of adding 150 mg bicalutamide to standard care, that is radical prostatectomy, radiotherapy or watchful waiting (WW), in patients with localized or locally advanced prostate cancer. MATERIALS AND METHODS: A total of 1,218 men with T1-4, M0, any N prostate cancer were recruited from 62 Scandinavian centers and randomized 1:1 to 150 mg bicalutamide or placebo plus standard care. Primary end points were progression-free survival (PFS) and overall survival. RESULTS: At a median 5.3-year followup patients with locally advanced disease had improved survival with bicalutamide (HR 0.68, 95% CI 0.50 to 0.92), while those with localized disease had decreased survival with bicalutamide (HR 1.47, 95% CI 1.06 to 2.03). Bicalutamide significantly improved PFS, decreasing the risk of disease progression by 43% compared with placebo (HR 0.57, 95% CI 0.48 to 0.68, p<0.0001). The rate of events was 35.4% for bicalutamide and 46.2% for placebo. Patients with locally advanced disease gained the greatest PFS benefits with bicalutamide (HR 0.40, 95% CI 0.31 to 0.52). Since 81% of the trial population were untreated before entry and would otherwise have undergone WW, the findings essentially reflect the results of immediate hormone therapy vs WW. CONCLUSIONS: Bicalutamide (150 mg) provides significant benefit in patients with locally advanced disease. In previously untreated patients there may be a tumor burden below which endocrine therapy provides no benefit or may even decrease survival.

Aged↗
PubMed2004

Bicalutamide 150 mg in addition to standard care in patients with localized or locally advanced prostate cancer: results from the second analysis of the early prostate cancer program at median followup of 5.4 years.

PURPOSE: We evaluated the efficacy and tolerability of 150 mg bicalutamide daily given in addition to standard care, in patients with localized or locally advanced prostate cancer. MATERIALS AND METHODS: The bicalutamide Early Prostate Cancer program consists of 3 randomized, double blind, placebo controlled trials prospectively designed for combined analysis. A total of 8,113 men with T1b-T4, M0, any N (N0 in 1 trial) prostate cancer were randomized to bicalutamide 150 mg/day (4,052) or placebo (4,061) in addition to standard care (radical prostatectomy, radiotherapy or watchful waiting). Primary end points were objective progression-free survival (PFS) and overall survival. RESULTS: At median 5.4 years of followup (21.6% progression events) bicalutamide significantly improved PFS in the overall population. This result was driven by positive results in trials 24 and 25, with the North American trial (trial 23) showing no difference. Patients with locally advanced disease gained most benefit from bicalutamide in terms of PFS, irrespective of underlying therapy. Overall survival was similar in the bicalutamide and placebo groups, across the program and in each trial. Among watchful waiting patients survival appeared to be improved with bicalutamide in those with locally advanced disease, whereas survival appeared to be reduced with bicalutamide in those with localized disease. The most common adverse events with bicalutamide were gynecomastia and breast pain. Other adverse events occurred with a similarly low incidence in the 2 treatment groups. CONCLUSIONS: This analysis confirms that bicalutamide provides benefit in patients with locally advanced disease. The current data suggest that early or adjuvant hormonal therapy for patients at low risk of disease progression, such as those with localized disease, is not appropriate.

Adult↗