allylestrenol and Prostatic-Neoplasms

In the treatment of prostatic carcinoma, administration of some therapeutic agents, e.g. hormones, continuously as a basal treatment, and other proper treatment, e.g. irradiation or chemotherapy or both, were combined for occasional recurrence of the disease as additional treatment. Effectiveness of 5-fluorouracil in combination with hormones (estrogen or gestagen) in low doses, as a basal treatment, was compared with that of hormones alone in high doses. 5-Fluorouracil at 200 mg/day doses combined with gestagen (allylestrenol or chloromadinone acetate) at 50 mg/day doses was compared with estrogen (hexestrol) at 60 mg/day doses in 30 randomized patients with previously untreated prostatic carcinoma. On the other hand, 5-fluorouracil at 200 mg/day doses combined with hexestrol at 30 mg/day doses was compared with hexestrol at 60 mg/day doses also in 26 randomized patients with carcinoma already well controlled by hexestrol at 60 mg/day doses for more than two years. In patients of the former group treated with 5-fluorouracil and gestagen the rate of recurrence was 20%, mean effective period of therapy was 69 months and 5-year survival rate was 73%, although, in patients treated with high dose estrogen, the rate of recurrence was 60%, mean effective period was 43 months and 5-year survival rate was 55%. At occasional recurrence of the disease, in nearly half the patients in both groups, the disease responded to additional treatments and remission was obtained again. In patients of the latter group with already well controlled disease, no significant difference in prognosis was observed between patients treated with 5-fluorouracil plus low dose estrogen and those treated with high dose estrogen alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Allylestrenol; Combined Modality Therapy; Drug Therapy, Combination; Estrenes; Fluorouracil; Hexestrol; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms

Molecular basis for secondary antiandrogen therapy in prostate cancer with mutant androgen receptors (ARs) is not fully elucidated.. Effects of steroidal and non-steroidal antiandrogens on transcriptional activities of wild-type and mutant (W741C, T877A, and W741C+T877A) ARs were measured. Crystal structure analysis and docking studies were performed using Molecular Operating Environment (MOE) package.. DHT-induced transcriptional activity of the T877A mutant and the W741C mutant was suppressed by bicalutamide and hydroxyflutamide, respectively. Nilutamide suppressed the W741C mutant and the double mutant. Cyproterone acetate modestly inhibited the W741C mutant and the double mutant. The structural studies suggested that nilutamide and cyproterone acetate retain their antiandrogenic properties against both the W741C mutant and the double mutant due to fact that mutation W741C does not permit formation of key hydrophobic interaction between ligand and AR ligand binding domain, which is necessary for their conversion into agonists.. Switching antiandrogens may be reasonable in prostate cancer with mutant ARs.

Topics: Allylestrenol; Androgen Antagonists; Androgen Receptor Antagonists; Androgens; Anilides; Cyproterone Acetate; Flutamide; Humans; Imidazolidines; Male; Models, Molecular; Mutagenesis, Site-Directed; Neoplasms, Hormone-Dependent; Nitriles; Plasmids; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Testosterone; Tosyl Compounds; Transcription, Genetic; Transfection

A trial to reduce the dosage of estrogen or to substitute it by other agents was done as a treatment of prostatic carcinoma. Either the combination of 5-FU (200 mg/day) and allylestrenol (50 mg/day), or 5-FU and hexestrol (20 mg/day) was given to 24 cases of prostatic carcinoma, 4 of whom were relapsed hormonal-resistant cases, 14 cases were controlled by large doses of estrogen and 6 were newly treated cases. No progressions were observed following 3 months of therapy. In 5 cases, progression was observed after 6 months. Deteriorated cases increased to 6 cases after 12 months. The effective rate, according to the "vital score," which is proposed as a parameter of the physical condition of patients with prostatic carcinoma, was calculated to be 100% at 3 months, 77% at 6 months, and 71% at 12 months.

Topics: Aged; Allylestrenol; Drug Therapy, Combination; Estrenes; Fluorouracil; Hexestrol; Humans; Male; Middle Aged; Prostatic Neoplasms