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

Between March 1986 and March 1987, 48 patients with stage D prostate carcinoma were entered into a multicentric pilot study using the pure nonsteroidal antiandrogen nilutamide (Anandron--RU 23908) at the dose of 100 mg t.i.d. as the only therapy until disease progression or the occurrence of toxicity. Minimum follow-up was 15 months. Median age of patients was 72 (56 to 83) and median initial Performance Status (PS) was 1 (0 to 3). Of the 48 patients, 29 were untreated, while 19 patients were progressing following treatment by orchiectomy, LHRH analogs, or other endocrine therapies. According to the National Prostatic Cancer Project (NPCP) criteria, 43 patients were evaluable for response. Overall best response in untreated patients was partial response (PR), 41.6%; stationary disease (SD), 54.1%; 73.6% of pretreated patients achieved SD. Median progression-free survival and overall survival in untreated patients were 325 and 696 days, respectively, and 174 and 447 days, respectively, in pretreated patients. The more common side effects were G.I. toxicity (65%), hemeralopia (27%), and alcohol intolerance (6.2%). Results of this study suggest that Anandron may be a safe and effective treatment for patients with advanced prostatic cancer.
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PMID:Anandron (RU 23908) in metastatic prostate cancer: preliminary results of a multicentric Italian study. 178 40

In conclusion, the intergroup study in the US, as well as preliminary results of the Anandron and leuprolide study, would support the view that combined androgen blockade is better than monotherapy in achieving clinical responses, prolonging the time to progression, and improving the survival rate. This improvement in survival rate is not a huge advance but is a step in the right direction. Future clinical trials are needed to evaluate newer methods to improve survival rates. The results also open up the possibility of employing this combined androgen blockade in earlier stages of prostate cancer in order to delay progression of the cancer and perhaps improve patient survival. Only carefully constructed clinical trials will be able to answer these questions.
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PMID:Total androgen ablation: American experience. 189 95

A multicenter, randomized double-blind study was carried out in 203 patients with metastatic prostate cancer, in order to compare the efficacy of complete suppression of androgens achieved with surgical castration and nilutamide (Anandron), 100 mg t.i.d. The combined therapy was well-tolerated by patients, and they noted a better relief of bone pain after six months than those in the control group. There was a greater number of favorable responses in the combined treatment group. In addition, despite a similar median progression-free actuarial rate, the combined treatment (nilutamide plus orchiectomy) offered an improved survival time over orchiectomy alone.
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PMID:Combination of Anandron with orchiectomy in treatment of metastatic prostate cancer. Results of a double-blind study. 199

Antiandrogens, substances that prevent androgens from expressing their activity at target cells, play an important role in the treatment of prostate cancer. The most frequently used substances have either a steroidal structure (cyproterone acetate) or a non-steroidal structure (Flutamide or Anandron). Antiandrogens have been tested both alone and in combination with treatments aimed at inhibiting testicular secretion (castration, LH-RH analogs), thereby producing complete blockade of androgen secretion and action. Patients treated by such combination protocols have often shown an improvement in the percentage of remissions and, less often, improvement in survival. Administration of antiandrogens improves the clinical symptoms of patients with benign prostatic hypertrophy, but the exact mechanism of their action requires further investigation. Cutaneous manifestations due to hyperandrogenicity (hirsutism, alopecia, acne) have also been improved by cyproterone acetate, which is often given together with estrogens (reversed sequential regime), by spironolactone or topically applied products. Finally, antiandrogens have been successfully used to treat breast cancer in men, early puberty, hypersexuality and sexual deviations.
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PMID:Clinical applications of antiandrogens. 246 32

We examined androgen modulation of proliferation of clonally derived AXC/SSh rat prostate cancer cells. C-family cells were maintained on medium without addition of androgens. D-family cells were maintained on medium containing 10(-7) M 5 alpha-dihydrotestosterone and T-family cells were maintained on medium containing 10(-7) M testosterone. Proliferation of all AXC/SSh prostate cancer cell lines during propagation on media containing fetal bovine serum was not altered by changes in media testosterone concentration through the range 10(-6) to 10(-9) M. Similarly, proliferation of C- or D-family cell lines, during propagation on media containing steroid depleted, charcoal stripped fetal bovine serum, was not altered by changes in media testosterone concentration through the range 10(-6) to 10(-9) M. By contrast, proliferation of T-family cell lines during propagation on charcoal stripped fetal bovine serum was modulated by androgens; effects were androgen concentration dependent and maximum at 10(-8) to 10(-7) M. Androgens decreased T5 cell proliferation rate and diminished achievable saturation density, whereas T1 cell proliferation rate was increased by androgens. In contrast, T6 cell proliferation rate was unaffected by androgens; however, saturation density was increased. Effects were antagonized by the antiandrogen RU 23908, Anandron, establishing androgen specificity of testosterone or 5 alpha-dihydrotestosterone mediated changes in proliferation.
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PMID:Differential androgen modulation of AXC/SSh rat prostate cancer cell proliferation in vitro and its antagonism by antiandrogen. 294 35

A randomized, double-blind, multicenter trial was performed comparing the association of orchiectomy plus the nonsteroid antiandrogen Anandron (300 mg daily) to orchiectomy plus placebo in the treatment of patients with stage C or D prostate cancer. The results for 98 evaluable stage D patients with a median follow-up of 23.4 +/- 8.9 months are given. Although there was no statistically significant difference between the two treatments with regard to any parameter (subjective response, best objective response according to NPCP criteria, and progression-free interval and survival), the results were invariably in favor of the combined treatment, as already reported in other trials on Anandron.
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PMID:Anandron (RU 23908) associated with orchiectomy in stage D prostate cancer. Preliminary results of a randomized, double-blind study. 307 52

Approximately 65% of patients with prostatic cancer treated by the combination therapy using a gonadorelin (LHRH) agonist or orchidectomy in association with the antiandrogen Anandron complained of a delay in recovering vision after bright illumination (sun, television, bright light). Detailed ophthalmological examination revealed an increase in the photostress recovery time to an average of 9 min, while the upper limit of normal is 1 min 20 s. When treatment was changed from Anandron to the other pure antiandrogen flutamide, the value of the photostress recovery time markedly decreased and the visual symptoms rapidly disappeared. Since uninterrupted administration of the antiandrogen is of the outmost importance for the successful therapy of prostatic cancer, the availability of a compound such as flutamide that has no side effect other than those due to hypoandrogenicity should greatly facilitate compliance by the patients and the success of the treatment.
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PMID:Ocular toxicity of Anandron in patients treated for prostatic cancer. 371 13

New N-substituted arylthiohydantoin antiandrogens were synthesized. These compounds presented exceptionally high relative binding affinities (RBAs) for the rat androgen receptor (AR): up to 3 times that of testosterone (T) and 100 times the RBAs of non-steroidal antiandrogens such as flutamide, Casodex and Anandron. Furthermore, unlike available markers for AR, they were totally devoid of any binding to the other steroid receptors. RU 59063, the molecule with the highest RBA, was tritiated. When it was compared to [3H]T for the assay of rat, mouse, hamster and human AR, it gave rise to the same number of binding sites but its K alpha (6 x 10(9) M-1) for rat and human AR were, respectively 3 and 8 times higher than that of T. Moreover RU 59063, unlike T, was devoid of any specific binding to human plasma. In vivo, these compounds displayed antiandrogenic activity while being devoid of any agonistic effect. Thus, RU 56187, given orally in castrated male animals, prevented in a dose-dependent manner the effects of 3 mg/kg testosterone propionate (TP) on mouse renal ornithine decarboxylase (acute test) and of 0.5 mg/kg TP on rat prostate weight (chronic test). In these two models, its ED50 was 0.6 and 1 mg/kg, respectively. In the intact rat, when given alone, it inhibited dose-dependently the effect of endogenous androgens on the seminal vesicles (ED50 approximately 1 mg/kg) and prostate (ED50 approximately 3 mg/kg) weights. These results suggest that these new compounds may be useful as specific markers for the androgen receptor as well as for the treatment of androgen-dependent diseases or disorders such as prostate cancer, acne, hirsutism and male pattern baldness.
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PMID:Non-steroidal antiandrogens: synthesis and biological profile of high-affinity ligands for the androgen receptor. 813 96

The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type of antiandrogen (flutamide, Anandron, or cyproterone acetate) added to castration. This paper reviews the different types of heterogeneity that might exist among trials that are involved in the overview: study design, randomization procedure, treatment evaluation, statistical evaluation, and data maturity. In order to overcome these various types of heterogeneity and to compare like with like, the treatment comparison should be stratified a posteriori by question (i.e., type of castration or type of anti-androgen studied) and by study. In this way, one may draw valid conclusions. Of course, those trials with a larger number of patients and a longer follow-up will contribute more to the overview's results.
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PMID:Comparability of prostate trials. 825

Casodex (bicalutamide, Zeneca Limited) is a nonsteroidal competitive inhibitor of androgens at the androgen receptor. The drug was developed to fulfil a number of needs for the treatment of prostate cancer. The specific aim was to demonstrate pharmacological activity, which would translate into clinical efficacy, good tolerability in the context of its use, oral availability, a convenient and forgiving dosing regimen, and clinical acceptability. Casodex has been shown to be orally bioavailable and well absorbed, with a plasma half-life of around 1 week. Although steady-state levels are not reached for 1 month, there is evidence that the androgen receptor blockade achieved with Casodex is equivalent to that of flutamide by the end of the first day. The dose of Casodex was established in a series of dose-ranging studies using the surrogate endpoints of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA). Initial studies suggested that a dose of 50 mg daily gave a fall in PAP equivalent to that seen with castration. This dose was, therefore, evaluated as monotherapy and subsequently as a component of combined androgen blockade. Higher doses were evaluated using PSA as a surrogate endpoint and, although doses up to 450 mg have been given to man, 150 mg daily is well tolerated with demonstrable evidence of activity. Although trials of the drug at 150 mg in monotherapy have, to date, not shown survival equivalence with castration, Casodex has been well tolerated with evidence of good symptomatic response and quality-of-life benefits including the potential of retaining libido. In combination treatment, Casodex is associated with significantly less gastrointestinal effects (diarrhoea) than the nonsteroidal antiandrogen flutamide (Eulexin, Schering-Plough International). Casodex is not associated with alcohol intolerance, pneumonitis and ocular defects which have been seen with the antiandrogen nilutamide (Anandron, Roussel). Moreover, since Casodex is a nonsteroidal antiandrogen, no steroidal effects have been seen.
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PMID:Clinical progress with a new antiandrogen, Casodex (bicalutamide). 871 70


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