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Biomedical subjects

P Iversen

Publications and source records attributed to P Iversen.

At least 55 records · Page 3Linked to original sources
PubMed1998

Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer: results from two multicenter randomized trials at a median follow-up of 4 years.

OBJECTIVES: To compare the efficacy, tolerability, and quality of life benefits of bicalutamide (Casodex) 150-mg/day monotherapy and castration in previously untreated nonmetastatic (M0) advanced prostate cancer. METHODS: A total of 480 patients with Stage T3/T4 nonmetastatic disease randomly received oral bicalutamide 150 mg/day or castration (either bilateral orchiectomy or goserelin acetate [Zoladex] 3.6 mg every 28 days) in a 2:1 ratio in two open multicenter studies (studies 306 and 307). The design of these studies was similar to allow a pooled analysis. RESULTS: In the combined survival analysis, at median follow-up of 202 and 205 weeks in studies 306 and 307, respectively, with 31% of the cases resulting in death, bicalutamide 150-mg monotherapy was statistically equivalent to castration; the risk of death from any cause was 7% less with bicalutamide than with castration (hazard ratio [HR] = 0.93). Data on time to treatment failure and objective progression could not be pooled, as results for these end points differed between the trials. In study 306, bicalutamide 150-mg monotherapy increased time to objective progression (HR = 0.58; P = 0.033) and treatment failure (HR = 0.66; P = 0.074), whereas in study 307, time to progression (HR = 1.35; P = 0.0471) and treatment failure (HR = 1.24; P = 0.097) favored castration. Bicalutamide therapy showed significant advantages over castration for both sexual interest (P = 0.029) and physical capacity (P = 0.046). Bicalutamide 150-mg monotherapy was well tolerated. CONCLUSIONS: Bicalutamide 150-mg monotherapy provides a similar survival outcome to castration in previously untreated patients with nonmetastatic advanced prostate cancer and confers statistically significant benefits over castration with respect to sexual interest and physical capacity.

Aged↗
PubMed1998

Seminal plasma PSA in spinal cord injured men: a preliminary report.

OBJECTIVE: The aim of the study was to evaluate the impact of spinal cord injury on seminal plasma PSA concentration. MATERIAL: Semen obtained from normal controls (n = 20) and patients (n = 16) with spinal cord injury. RESULTS: The concentration of prostate specific antigen in seminal plasma depended on the level of spinal cord injury, with significantly lower concentrations in patients with spinal cord lesions below T7 compared to both normal age-matched controls (P = 0.007) and patients with spinal cord injuries at or above T7 (P = 0.017). CONCLUSIONS: The results add to the previously reported observations of the possible impact of neurogenic stimulation on prostate activity. More studies of neurogenic stimulation in prostate growth and development are warranted to further elucidate the possible impact of neurogenic factors in the development of prostatic diseases.

Adult↗
PubMed1998

A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer.

OBJECTIVES: To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer. METHODS: A total of 1,453 patients with either confirmed metastatic disease (M1), or T3/T4 non-metastatic disease with elevated prostate-specific antigen (M0) were recruited into one of two identical, multicentre, randomised studies to compare 'Casodex' 150 mg/day with castration. The protocols allowed for combined analysis. RESULTS: At a median follow-up period of approximately 100 weeks for both studies, 'Casodex' 150 mg was found to be less effective than castration in patients with metastatic disease (M1) at entry (hazard ratio of 1.30 for time to death) with a difference in median survival of 6 weeks. In symptomatic M1 patients, 'Casodex' was associated with a statistically significant improvement in subjective response (70%) compared with castration (58%). Analysis of a validated quality-of-life questionnaire proved an advantage for 'Casodex' in sexual interest and physical capacity. 'Casodex' had a substantially lower incidence of hot flushes compared to castration (6-13% compared with 39-44%) and the most commonly reported adverse events were those expected for a potent antiandrogen. However, in patients with M0 disease at entry, the data are still immature with only 13% of M0 patients having died. An initial analysis of this immature data has suggested that the results in these patients may be different to those obtained in patients with M1 disease. A further survival analysis in patients with M0 disease is therefore planned when the data are more mature. CONCLUSIONS: 'Casodex' 150 mg is less effective than castration in patients with M1 disease. However, 'Casodex' has shown a benefit in terms of quality of life and subjective response when compared to castration and has an acceptable tolerability profile. Thus 'Casodex' 150 mg monotherapy is an option for patients with M1 prostate cancer for whom surgical or medical castration is not indicated or is not acceptable.

Aged↗
PubMed1998

Orchidectomy and oestrogen therapy revisited.

Over the past 20 years therapeutic options for prostate cancer have increased. Nevertheless, there may still be a role for long-established treatments such as orchidectomy and oestrogens. Orchidectomy is a simple surgical procedure, and patient survival is comparable with other treatments involving androgen ablation. However, loss of libido and sexual function is an expected outcome and hot flushes occur in about 50% of patients. Osteoporosis, loss of muscle mass, and the psychological impact associated with orchidectomy are of concern, particularly with increasing treatment periods. Nevertheless, orchidectomy is indicated when an immediate reduction of testosterone levels is required, or the patient does not comply with other treatments or objects to the cost of medical therapy. Oestrogen therapy may be superior to castration in terms of efficacy, but orally administered oestrogens are associated with gynaecomastia, loss of sexual function and unacceptable cardiovascular toxicity. Low dose oestrogens in combination with antiandrogens or antithrombotic agents may be better tolerated treatments. The route of administration is a crucial factor in the genesis of cardiovascular toxicity and parenterally administered oestrogens may not entail the same risk. Further research in this area is warranted.

Androgen Antagonists↗
PubMed1997

[Prostate-specific antigen, acid phosphatases and rectal exploration in the diagnosis of prostatic cancer].

Eleven hundred and seven patients referred for urological evaluation including measurement of serumprostate specific antigen (PSA) measurement are reviewed. Prostate cancer was diagnosed in 105 patients. PSA was found to be superior to prostatic acid phosphatase in the discrimination between prostate cancer and benign prostatic conditions. In 105 patients with newly diagnosed prostate cancer, scintigraphic evidence of osseous metastases was found in thirty-seven. No patients with a serum PSA value less than three times the upper normal limit of the assay had a positive bone scan. Isotope bone scan can be omitted in these patients, if they are not considered candidates for curative treatment.

Acid Phosphatase↗
PubMed1997

[Prostatic cancer men under age 65. Occurrence and need for study].

Based on information from the nationwide Danish Cancer Registry, the development in prostate cancer incidence among Danish men under 65 years is reviewed. Changes in incidence rate, clinical stage and the number of possible candidates for radical treatment are discussed.

Adult↗
PubMed1997

Combination of antisense oligonucleotide and low-dose chemotherapy in hematological malignancies.

Current conventional chemotherapy for the treatment of hematological malignancies, although quite effective, has associated toxicities to normal tissue and organs, which is still a major dose limiting factor. In addition, high dose chemotherapy followed by autologous stem cell transplantation is limited by tumor cell contamination in the stem cell harvest. The use of conventional chemotherapy alone to purge these tumor cell contaminants is known to damage normal hematopoietic progenitor cells, resulting in delayed engraftment. The combination of antisense oligodeoxynucleotides (ODN) and low doses of chemotherapy offer a potential regiment which may lower the doses of conventional therapeutics required to effectively combat disease, thus lowering cytotoxicity experienced by normal cells. Transient downregulation of genes by ODN treatment, which are involved in the transformation or perpetuation of the cancerous disease state, can remove the growth and survival advantages exploited by tumor cells. Many groups are currently investigating this combination and have produced intriguing results. This review article discusses the current research investigating the combination of antisense ODN therapy with conventional chemotherapy in the treatment of hematological malignancies. Although further improvements in this strategy are required, the results thus far support a future for this strategy in clinical management of hematological malignancy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Estramustine phosphate versus placebo as second line treatment after orchiectomy in patients with metastatic prostate cancer: DAPROCA study 9002. Danish Prostatic Cancer Group.

PURPOSE: We compared the effect of 560 mg. estramustine phosphate daily to placebo as a supplement to standard palliative therapy in patients with progressive disease after bilateral orchiectomy as first line therapy for metastatic prostate cancer. MATERIALS AND METHODS: In a double-blind multicenter study 131 patients with progressing metastatic hormone refractory prostate cancer were randomized to receive 280 mg. estramustine phosphate 2 times daily versus placebo. End points were clinical progression and death. Adverse events, decrease in prostate specific antigen (PSA) and subjective response were also assessed. RESULTS: Adverse events were common in both groups but breast tenderness/gynecomastia and diarrhea were more frequent among patients in the estramustine phosphate group. Subjective responses were few (9 of 50 estramustine phosphate and 4 of 57 placebo cases, p = 0.15). Median observation time for survival was 43 months and 124 patients died. Median time to subjective progression and median overall survival did not differ significantly between the 2 groups at 4.6 and 9.4 months in the estramustine phosphate group versus 5.0 and 6.1 months in the placebo group. Of 61 patients in the estramustine phosphate group 29 achieved a reduction in PSA of more than 25% at 1 month of followup compared to only 3 of 68 receiving placebo. A decrease in PSA after 1 month correlated significantly with survival. CONCLUSIONS: Although this study did not prove estramustine phosphate to be superior to placebo in terms of protocol end points, it generates the hypothesis that prolonged survival may be achieved with estramustine phosphate treatment in a subgroup of patients and that this may be predicted by a decrease in PSA after 1 month of therapy.

Aged↗
PubMed1996

Randomised study of Casodex 50 MG monotherapy vs orchidectomy in the treatment of metastatic prostate cancer. The Scandinavian Casodex Cooperative Group.

The effect of Casodex (ICI 176,334), a new, once-daily, selective antiandrogen, given as 50 mg monotherapy, was compared with orchidectomy in a randomised, multicentre, open study in 376 patients with metastatic prostate cancer. At 3 months, PSA was reduced by 86% in the Casodex group and by 96% in the orchidectomy group. Treatment failed in 51 patients in the orchidectomy group and 66 showed a subjective response. Treatment failed in 86 patients treated with Casodex and 40 patients showed a subjective response. Patients treated with Casodex maintained their sexual interest better than those in the orchidectomy group. Median survival was significantly longer in the orchidectomy group. Casodex was well-tolerated. The most likely reason for the differences between the groups regarding time to treatment failure and survival is that the dose of Casodex was too small. Further studies with higher doses of Casodex are in progress.

Aged↗
PubMed1996

Advantages of raloxifene over alendronate or estrogen on nonreproductive and reproductive tissues in the long-term dosing of ovariectomized rats.

For the first time, raloxifene or alendronate was administered to rats immediately after ovariectomy for 10 months and compared with estrogen to elucidate mechanisms behind the raloxifene effects observed in nonreproductive and reproductive tissues. Specifically, 75-day-old rats were randomly selected as sham controls (Sham), ovariectomized controls (Ovx) or ovariectomized rats treated with fully efficacious doses of raloxifene (RA), 17 alpha-ethynyl estradiol (EE2) or alendronate (ABP). Lumbar vertebrae and proximal tibiae were examined by computed tomography (QCT) and by histomorphometry. Histomorphometry showed differences in bone architecture between groups when QCT densities were similar, but tibial trabecular bone analysis by QCT correlated with histomorphometry with r = .86 to .93, depending on the parameter. Both techniques confirmed that Ovx had substantially less bone than Sham, with greater loss of trabecular bone in the proximal tibia than vertebrae. Both techniques showed that RA had effects similar to but not identical with EE2 in preventing bone loss in vertebrae and tibiae. ABP partially prevented loss of bone in L-5, but was not significantly different from Ovx in the proximal tibia. This may be caused by ABP suppression of bone apposition, beyond effects observed for EE2 or RA. RA appeared to be more similar to EE2 because ABP significantly depressed bone formation (bone formation rate, mineral apposition rate) to below RA or EE2 levels, especially in L-5. Mechanical loading to failure of L-6 vertebrae showed a rank order of vertebral strength of Sham > RA > EE2 > Ovx > ABP, although significant differences were not observed between treatment groups. These data show that ABP suppression of bone formation can affect bone quality with long-term treatment. In other tissues, RA had minimal uterine effects, while significantly lowering serum cholesterol to below EE2-treated levels. Both EE2 and RA rats had significantly lower body weights than the other groups. ABP had no effect on serum lipids, uterine weight or body weight. Therefore, RA appears to have a broader range of desirable effects on bone, body weight, uteri and cholesterol than ABP or EE2 in ovariectomized rats.

Alendronate↗
PubMed1995

In vivo modulation of the rat cytochrome P450 1A1 by double-stranded phosphorothioate oligodeoxynucleotides.

CYP1A1 gene expression is regulated by known cis- and transacting elements controlling inhibition and induction of CYP1A1 transcription. The influence of a double-stranded phosphorothioate oligonucleotide (dsODN) with sequence identical to the CYP1A1 negative regulatory element (NRE) was examined in Sprague-Dawley rats. Two strategies were employed: (i) two single-stranded complementary 25-mer ODNs that form a double-stranded ODN (ODN1) and (ii) a 54-base, self-complementary ODN which forms a dsODN hairpin (ODN2). A dsODN hairpin with scrambled NRE sequence was evaluated as a control (ODN3). Zoxazolamine paralysis times, an in vivo marker of CYP1A1 activity, were reduced from 184 +/- 18 min in saline-treated rats to 103 +/- 12.5 min 24 hr after a single 1.7-mg ODN1 iv injection. Liver microsomal EROD, an in vitro marker of CYP1A1/2 activity, was increased from 210 +/- 10 pmol in saline-treated animals to 703 +/- 73 and 623 +/- 89 pmol resorufin/mg protein/min after iv ODN1 and iv ODN2, respectively. ODN1's activity did not change PNP hydroxylation and PROD, markers of CYPs 2E1 and 2B1/2. ODN2 did not significantly change PNP but did significantly alter PROD. The ODN3 did not cause any significant changes in any assay measured. The ODN1-induced responses in ZX paralysis and EROD were observed post-iv injection, but not following ip injection of ODN1. Western blot analysis of ODN1- and HPO-treated rat liver microsomes also revealed increased in CYP1A1 protein. These data indicate double-stranded ODNs mimic the cis-acting NRE in vivo inducing CYP1A1 in the absence of other xenobiotics.

Animals↗
PubMed1995

Management of early prostatic cancer in the Nordic countries: variations in clinical policies and physicians' attitudes toward radical treatment options.

To explore the treatment of patients with early localized prostatic carcinoma, we surveyed the departments of urology and general surgery in Denmark, Finland, Norway, and Sweden. Clinical policies and physicians' attitudes toward the radical treatment options varied widely between the countries. A correlation seems to exist between practice patterns and national attitudes toward special technologies.

Attitude of Health Personnel↗
PubMed1995

Collagen derived serum markers in carcinoma of the prostate.

Three new collagen markers deriving from the collagenous matrix, e.g. carboxyterminal propeptide of type I procollagen (PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), and aminoterminal propeptide of type III procollagen (PIIINP) were used for the diagnose of prostatic bone metastases. Blood samples were obtained prior to biopsy or TURP. Serum PICP, PIIINP and ICTP were measured with commercial available RIAs and PSA by IRMA. Serum PSA was increased in patients with local prostatic cancer compared with patients with hyperplasia (p < 0.05). The level of PIIINP, ICTP, and PICP did not differ between these two groups. In patients with metastatic prostatic cancer all five markers were increased compared to the level measured in patients with localized cancer (p < 0.0001). All variables showed a significant positive relationship with alkaline phosphatase. The sensitivity ranged from 0.53 to 0.62 and specificity from 0.91 to 0.95. The sensitivity for alkaline phosphatase and PSA was 0.69 and 0.66 and specificity 0.91 and 0.68, respectively.

Aged↗