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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assess stratum (e.g. treatment) interactions with covariates and with the baseline hazard function in the proportional hazards (PH) regression model for lifetime data. We consider models incorporating stratum interactions both with and without stratification of the risk sets in the likelihood function, and describe likelihood ratio statistics for tests of the presence of these interactions. We also present step-down methods for building reduced models which include stratum-specific parameters corresponding to covariates which interact with treatment. We apply PH models with such interactions to a clinical trial of DES in the treatment of prostate cancer to determine optimal treatment conditional on each patient's covariates.
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PMID:Assessment of stratum-covariate interactions in Cox's proportional hazards regression model. 351 75

In a randomized phase III trial performed by the Urological Group of the European Organization for Research on Treatment of Cancer low dose estramustine phosphate (280 mg. twice daily for 8 weeks and 140 mg. twice daily thereafter) was compared to diethylstilbestrol (1 mg. 3 times daily) in patients with stages T3 to T4, M0 or M1 prostatic cancer. Of 248 patients entered 227 were evaluable for analysis: 115 received estramustine phosphate and 112 received diethylstilbestrol. The best response of the local tumor as assessed by palpation was seen in patients receiving diethylstilbestrol. There was no significant difference between treatments for response rate of metastases, interval to local progression, distant progression, over-all survival and death of carcinoma of the prostate. Duration of survival was correlated with the assessment of local response as determined by palpation. The response of distant lesions also was correlated closely with survival. Diethylstilbestrol (1 mg. 3 times daily) was associated with a significantly worse degree of cardiovascular toxicity than estramustine phosphate. This finding was especially obvious in patients who had no history of cardiovascular disease. Gastrointestinal toxicity occurred in 25 patients treated with estramustine phosphate, including 6 in whom cessation of treatment was necessary. Further studies are required to determine the optimum dose of diethylstilbestrol and estramustine phosphate, and to establish the best form of hormonal treatment for prostatic carcinoma.
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PMID:A comparison of the effect of diethylstilbestrol with low dose estramustine phosphate in the treatment of advanced prostatic cancer: final analysis of a phase III trial of the European Organization for Research on Treatment of Cancer. 352 66

We compared the effect of a variety of drug regimens to lower prostate DHT concentration. Patients with BPH were treated for one week prior to surgery with either tamoxifen, flutamide, megestrol acetate, megestrol acetate plus tamoxifen and megestrol acetate plus DES or ketoconazole. DHT concentration in the surgically resected tissue was compared with tissues obtained from untreated patients. We also obtained prostate tissue at the time of relapse in patients with prostate cancer who had been treated with orchiectomy with or without estrogen therapy. Megestrol acetate plus the mini-dose of DES (0.1 mg) and megestrol acetate plus ketoconazole both decreased DHT concentrations in prostate tissue to levels (0.79 ng/g) significantly below those noted with orchiectomy (1.16 ng/g). The difference between the DHT concentration in the two groups (orchiectomy vs. total androgen blockade) represents the contribution of adrenal androgens to prostate tissue DHT. This small amount of DHT (approximately 0.4 ng/g) may be biologically important in stimulating prostate epithelial cell growth.
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PMID:Effects of castration compared with total androgen blockade on tissue dihydrotestosterone (DHT) concentration in benign prostatic hyperplasia (BPH). 362 49

Direct Determination of Diethylstilbestrol and its Monoconjugates in Plasma After "homogeneous ion pair extraction" with CH3OH from plasma of patients suffering from metastatic prostate cancer and subsequent partitioning on a C18-phase diethylstilbestrol (E-DES) and its monoconjugates (glucuronide, sulfate) as well as its glucuronide-sulfate conjugate may be detected quantitatively by HPLC/UV (236 nm) or HPLC/ED (+1.0 V). Working electrode is a special home-made carbon paste electrode. The range of detection is in the low ng range (2-5 ng/ml plasma); standard deviation is less than 5%. It is the first time that plasma levels of these metabolites of fosfestrol (Honvan) could be measured directly without prior hydrolysis.
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PMID:[Direct determination of diethylstilbestrol and its monoconjugates in plasma]. 371 1

Beside orchiectomy and estrogens, other endocrine manipulations are proposed for metastatic prostatic cancer patients. Antiandrogens, Cyproterone acetate and Flutamide, are often less efficient but less toxic than DES. Progestational agents medroxyprogesterone acetate, megoestrol acetate, chlormadinone acetate have also a limited activity. Inversely, tamoxifen is very little active. Preliminary results of ketoconazole need more controls. The present aims are to obtain, particularly by hormonal association, a more efficient and less toxic treatment, when DES can be given initially or becomes inefficient.
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PMID:[Cancer of the prostate: new hormone therapies]. 377 22

Chemilumenescence (CL) occurs due to the phagocytosis of bacteria and of tumor cells by polymorphonuclear neutrophils (PMN). Levels of CL were measured in patients with prostatic cancer and from normal subjects. Patients with advanced disease (stage C, D) showed no elevated CL levels as compared to healthy individuals or patients with minimal disease (stage A, B). Following external radiation therapy in patients with stage A-C prostatic carcinoma high levels of CL were recorded. Estrogen medication also resulted in increased CL levels, while estramustine did not affect phagocytic activity. Intradermal BCG vaccination caused increased PMN activity. Progressive prostatic cancer in hormone treated patients was associated with increased CL as compared to patients with stable or regressive disease.
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PMID:Activity of phagocytic granulocytes in patients with prostatic cancer. 381 Oct 82

Hormonal therapy for metastatic prostate cancer blocks the androgen-mediated action that stimulates the hormone-dependent clone of tumor cells. Such therapy must be directed at all sources of tissue dihydrotestosterone (DHT), including testosterone derived from the testis. Adrenal androgens such as dehydroepiandrosterone (DHEA) sulfate, DHEA, and androstenedione may also diffuse into prostate cells, and although their conversion to DHT is in the range of only 3% to 7% (compared to 50% to 70% for testosterone), the large amount (four to six times that of testosterone) of adrenal androgen substrate may account for up to one sixth of total prostate DHT. The role of adrenal androgens as potential stimuli to the hormone-dependent clone of tumor cells is further supported by studies in which significant amounts of DHT were found in the prostates of patients in clinical relapse after surgical castration. There are reports indicating that both surgical and medical adrenalectomy produce subsequent remissions in about 30% of patients who failed after castration or estrogen. The rationale to suppress all sources of DHT, therefore, is clear. To accomplish this goal successfully, megestrol acetate was combined with DES or estradiol to suppress testicular function to castration levels and to block residual adrenal androgens at the cell level. Studies are underway to compare clinical disease-free intervals in these patients to those patients receiving traditional therapy of castration and estrogen.
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PMID:Rationale for blockade of adrenal as well as testicular androgens in the treatment of advanced prostate cancer. 388 2

In 24 untreated stage D2 prostate cancer patients with prostate DHT levels greater than 2.5 ng/g, 20 initially responded to therapy with partial objective progression (POR) or were objectively stable (OS) for 12 or more months while four patients relapsed in less than 1 year. Of eight patients with prostate DHT levels less than 2.0 ng/g, five had either objective progression or were objectively stable for 6 months or less; two other patients have completed remissions ranging from 16 to 24 months while one patient remains objectively stable for 21 months to date. DHT concentrations were also measured in prostate tissue of patients with advanced prostate cancer in relapse following either DES or castration with or without estrogen therapy. Although castration, medical or surgical, usually leads to DHT concentrations of less than 2.4 ng/g, two out of 20 surgical castrates and four out of nine estrogen-treated patients had values above this level. These differences suggest that (1) increased tissue DHT levels of DES-treated patients may be due to inadequate dosage or decreased compliance, and (2) increased tissue DHT concentrations greater than 2.4 ng/g in castrates suggests an adrenal cortical androgen contribution to the prostate DHT level. These studies suggest that DHT measurements in prostate cancer tissue are of value in predicting response in untreated prostate cancer patients and of directing therapy in patients who are in relapse after orchiectomy or estrogen therapy.
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PMID:DHT in prostate cancer tissue--a guide to management and therapy. 396 70

Twenty-five patients with metastatic prostate cancer resistant to primary hormone therapy, received high-dose intravenous diethylstilbestrol diphosphate (Stilphostrol [Miles Pharm], DES-P) in a Phase II study using established response criteria. Objective response rate was 17%, while 22% of the patients were subjectively improved. Moderate gastrointestinal toxicity was reported in 10 patients (40%). Thromboembolic complications were seen in 2 (8%). The role of high-dose Stilphostrol in the treatment of hormone-resistant prostate cancer is limited.
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PMID:A phase II study of high-dose estrogens (diethylstilbestrol diphosphate) in prostate cancer. 400 8

An alternative program for medical castration for treatment of prostate cancer has been developed using a progestational antiandrogen, megestrol acetate (MA), in combination with small doses of diethylstilbestrol (DES; 0.1 mg/day). The administration of MA (40-80 mg/day) with 0.1 mg DES to nine patients resulted in castrate levels of plasma testosterone (less than 0.4 ng/ml) and significant suppression of both FSH and LH (P less than 0.05) for up to 12 months. Although large clinical trials must ultimately establish its safety, clinical side effects of this combined therapy to date have consisted of mild gynecomastia in two patients. The symptoms did not necessitate discontinuing the medications. It is concluded that the use of 0.1 mg DES with a minimum of 40 mg/day MA results in medical castration with sustained suppression of plasma testosterone. Because of the possible additional therapeutic advantage of blockade of intracellular androgen-mediated action by MA in androgen-dependent tumors, this combined therapy should be further explored as a possible initial treatment of choice for advanced prostate cancer.
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PMID:Medical castration of males with megestrol acetate and small doses of diethylstilbestrol. 616 42


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