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Biomedical subjects

H J de Voogt

Publications and source records attributed to H J de Voogt.

At least 19 recordsLinked to original sources
PubMed1998

Maximum androgen blockade using LHRH agonist buserelin in combination with short-term (two weeks) or long-term (continuous) cyproterone acetate is not superior to standard androgen deprivation in the treatment of advanced prostate cancer. Final analysis of EORTC GU Group Trial 30843. European Organization for Research and Treatment of Cancer (EROTC) Genito-Urinary Tract Cancer Cooperative Group.

This is the final analysis of EORTC GU Group Trial 30843 in which the treatment of advanced, metastatic prostate cancer with a combination of the LHRH agonist buserelin (nasal spray) and cyproterone acetate (Androcur), either continuously of only during the first 2 weeks, was compared with orchidectomy. There was no significant difference between the three arms as far as response rate, time to progression (subjective and objective) and duration of survival are concerned. Retrospective stratification according to the most important prognostic factors did not change the conclusions. Possible reasons for the difference with trial 30853, which used the same entry criteria but compared goserelin and flutamide with orchidectomy, are discussed. Reasons for using cyproterone acetate in combination treatment are the prevention of flare of the disease after LHRH agonists only and the prevention/reduction of toxicity in the form of hot flushes.

Acid Phosphatase↗
PubMed1993

Short-term versus long-term addition of cyproterone acetate to buserelin therapy in comparison with orchidectomy in the treatment of metastatic prostate cancer. European Organization for Research and Treatment of Cancer--Genitourinary Group.

In an open, multicenter, three-armed, randomized study, we compared the effects of short-term (2 weeks) and continuous addition of the antiandrogen cyproterone acetate to the luteinizing hormone-releasing hormone agonist buserelin to those of orchidectomy in patients with advanced prostate cancer. No significant differences among the three treatment arms with respect to response rate, subjective response, time-to-progression, overall survival, and cancer deaths were observed. It was concluded that the short-term or continuous addition of cyproterone acetate to buserelin administered intranasally did not improve treatment results compared to orchidectomy only.

Adult↗
PubMed1992

The position of cyproterone acetate (CPA), a steroidal anti-androgen, in the treatment of prostate cancer.

Cyproterone acetate is a steroidal anti-androgen that blocks the androgen-receptor interaction and reduces serum testosterone through its weak anti-gonadotropic action. It can be regarded as the only anti-hormone that causes complete androgen blockade as monotherapy. Many animal experiments and several clinical phase II and phase III trials have demonstrated that it deserves a place in the endocrine therapy of advanced prostate cancer, particularly for those patients who find orchidectomy unacceptable and who do not have known cardiovascular risks. Additionally, cyproterone acetate can be used safely to prevent disease flare when a luteinizing hormone releasing hormone analog is the drug of choice and to suppress hot flashes in response to LHRH agonists or after orchidectomy.

Androgen Antagonists↗
PubMed1991

The use of the LHRH-analogue Buserelin in the treatment of prostatic cancer. A 10-year review on 1522 patients treated in 119 centres on 4 continents.

In the ten years from 1979-1988, a total of 1725 patients with advanced prostatic cancer were entered into 28 studies, in which Buserelin as a nasal spray was the main androgen deprivation therapy. Patients treated with orchiectomy or other anti-androgen agents used in comparative groups, were considered unsuitable for the purpose of this study, which pools the data of the 1522 patients who received Buserelin monotherapy. Patients with stages C, D1 or D2 prostatic cancer who received Buserelin as monotherapy and had a known treatment duration were eligible for efficacy analysis. The clinical evaluation was done in 91% by NPCP-criteria and in the remainder by criteria of the EORTC or ECOG. Seventy-five per cent of the patients received Buserelin nasal spray (3x daily 400 mcg), 20% received subcutaneous injections (2x daily 200 mcg) and 4% received 2 combinations of nasal spray, subcutaneous injections and depot, or depot alone. Compliance failures were found in 4.4% and 2.4% stopped treatment due to adverse reactions. Statistical analysis includes Kaplan-Meier estimates of time-to-progression and survival. Since 1985, after 2 patients died from possible fare reactions, anti-androgens have been recommended as additional therapy for the first few weeks. Features of this analysis of great interest are the national differences in progression-free survival and overall survival.

Buserelin↗
PubMed1990

Orchidectomy versus Buserelin in combination with cyproterone acetate, for 2 weeks or continuously, in the treatment of metastatic prostatic cancer. Preliminary results of EORTC-trial 30843.

This prospective randomized phase III trial compares orchidectomy as standard androgen-deprivative therapy of advanced (metastatic) prostatic cancer with treatment using the LHRH agonist Buserelin administered as nasal spray 3 daily doses of 400 micrograms, and combined with cyproterone acetate (CPA) 3 daily doses of 50 mg orally for 2 weeks initially to prevent flare-up of the disease, or continuously as complete androgen blockade. The trial was closed to entry in September 1989 when 367 patients were recruited. Patients were stratified for performance status (WHO) and metastatic status prior to randomization. According to patient and disease characteristics spreading of patients over the 3 arms was without statistical significant differences. Ineligibility was 5 and 4% of the patients were only partly evaluable. In March 1990 a first, preliminary analysis was performed. At that time 207 patients were off-study for progression or death and median follow-up was 1 yr. As to time-to-progression and survival there were no significant differences between the 3 arms. The meaning of this in regard to results of other trials with complete androgen blockade is discussed.

Aged↗
PubMed1990

The prognostic significance of selective nuclear morphometry in urinary bladder carcinoma.

Transurethral resected tumor specimens of 61 patients with a primary and untreated bladder carcinoma were studied by selective nuclear morphometry, a method recently described by us. A significant enlargement of the mean nuclear area was found with the advance of tumor grade and stage (Wilcoxon, P less than .0001 and P less than .0001). The heterogeneity of the grade 2 patient group and the additional value of morphometry were demonstrated by observing the 5-year survival rates. Patients with grade 2 carcinoma could be separated into one subgroup with small nuclei (mean nuclear area less than or equal to 95 microns2) having a favorable outcome (5-year survival rate: 100%), and into another subgroup with large nuclei (mean nuclear area greater than 95 microns2) showing a worse prognosis (5-year survival rate: 63.2%) (Mantel-Cox, P = .01). The outcome of these subgroups was not significantly different from that of the grade 1 (5-year survival rate: 93.8%) and grade 3 (5-year survival rate: 50%) patients, respectively (Mantel-Cox, P = .45 and P = .57). The value of selective nuclear morphometry, in addition to tumor staging, was indicated by the association of nuclear enlargement (mean nuclear area greater than 95 microns2) with progressive recurrence (five of 15 patients; 33%) among the patients with conservatively treated superficial carcinoma (stages Ta and Tl). The findings demonstrate the supplementary value of selective nuclear morphometry to tumor grading and staging, especially in the heterogeneous group of grade 2 carcinomas and the group of superficial tumors (stages Ta and Tl).

Aged↗
PubMed1990

Reversibility of the effect of LHRH agonists and other antiandrogenic hormones on the testis: a histomorphometric study.

Changes in testicular morphology are quantified in patients with metastatic prostatic cancer, treated with LHRH agonist Buserelin and compared with testes of young transsexuals and patients with metastatic prostatic cancer treated with orchidectomy only. No significant changes within 18 months were seen, suggesting reversibility of LHRH agonist effects on testicular morphology in this time period. Histomorphometrics of the testis are useful to quantify these changes.

Adult↗
PubMed1989

Comparison of quantitative and classic prognosticators in urinary bladder carcinoma. A multivariate analysis of DNA flow cytometric, nuclear morphometric and clinicopathological features.

The prognostic value of nuclear morphometry and DNA flow cytometry of paraffin embedded material of 58 patients with primary and untreated transitional cell carcinoma of the bladder was compared with that of histological grade (WHO-system), tumour stage (TNM-classification), tumour size, multiplicity and ulceration. Small nuclear size (mean nuclear area less than or equal to 95 microns2) (n = 25) and DNA diploidy (n = 28) indicated a favourable outcome (5-year survival 95.8% and 92.2%); large nuclei (mean nuclear area greater than 95 microns2) (n = 33) and DNA aneuploidy (n = 30) indicated a worse prognosis (5-year survival 61.4% and 62.5%) (Mantel-Cox; p = 0.002 and p = 0.007). The quantitative techniques had the advantage over subjective histological grading that distinguishment of an intermediate patient group (WHO-system: grade 2; n = 32) with heterogeneous outcome (5-year survival 78%) was avoided. Multivariate analysis showed tumour stage as the most important prognosticator of survival. Neither the quantitative techniques, nor the other classic features added significantly to the prediction. The additional value of the quantitative techniques was however shown in superficial carcinoma (TNM-classification: stage Ta and T1; n = 37); large nuclei (mean nuclear area greater than 95 microns2) (n = 15) and aneuploid DNA peaks (n = 13) were associated with progressive recurrent tumour (n = 7) (Mantel-Cox: p = 0.03 and p = 0.0004). The quantitative methods thus indicate which patients are at risk for progression and may enable more appropriate treatment at an earlier stage of disease.

Aged↗
PubMed1989

Multivariate analysis of prognostic factors in patients with advanced prostatic cancer: results from 2 European Organization for Research on Treatment of Cancer trials.

The European Organization for Research on Treatment of Cancer Genitourinary Group performed a multivariate statistical analysis of prognostic factors based on 436 patients entered between 1976 and 1981 in 2 randomized prospective trials that compared 4 different hormonal treatment regimens. Only previously untreated patients with advanced (stage T3/T4/M0 or M1) prostatic cancer were eligible. After identification of prognostic factors by means of univariate analyses a multivariate analysis using Cox's proportional hazards regression model was done. This test identified performance status (according to the Eastern Cooperative Oncology Group scale) as the most important factor, followed by acid phosphatase (more than 2 times normal) for stage M0 cancer patients, and alkaline phosphatase, T category and the presence or absence of associated chronic disease for stage M1 cancer patients. Based on these 4 variables nonbedridden patients with metastatic disease can be divided into 2 groups: poor and good risk patients, with median survivals of 1 and 3 years, respectively. This study shows that routine clinical and laboratory data already provide an excellent indication as to the prognosis.

Adult↗
PubMed1988

Efficacy and advantages in the use of low doses of Anandron and estrogen combination in the treatment of prostate cancer.

Treatment effects of RU 23908 antiandrogen (Anandron) and estrogen in low doses on hormone-dependent rat prostatic adenocarcinoma (R3327-H) were investigated. Tumor-bearing Copenhagen rats were treated for 6 weeks with 8 micrograms Anandron and 1 microgram estradiol-17 beta every two days. Reduction and counteraction of androgen synthesis and action was established by an observed decline in serum testosterone level and by changes in both histology and weight of androgen target organs. Prostate tumor growth rate was significantly retarded in rats treated with Anandron/Estradiol combination compared to untreated intact control and was equal to the slow growth rate in castrate tumor-bearing animals. Tumor histology changes during treatment correlated with the observed growth rate retardation. Areas of necrosis, metaplasia, and acellularity were more frequently observed in tumors of Anandron/Estradiol-treated compared to castrated rats. These results suggest that low doses of Anandron and estrogen can effectively be combined as a complete androgen counteracting therapy for hormone-dependent prostatic carcinoma with minimal undesired side effects.

Animals↗