Estramustine Phosphate Sodium

摘要: Estramustine phosphate sodium (estramustine phosphate), a unique antitumour agent, is selectively taken up by prostate cells and exerts antineoplastic effects interfering with microtubule dynamics reducing plasma levels of testosterone. In noncomparative studies estramustine in patients hormone-refractory disease, objective response rates ranging from 19 to 69% have been reported. Preliminary clinical investigations indicate that combining vinblastine, etoposide or paclitaxel improves over single-agent treatment, although no survival benefit treatment has demonstrated date. comparative studies, produces similar conventional agents cancer. previously untreated advanced metastatic hormone-responsive cancer, responses are achieved approximately 80% patients. appears be at least as effective estrogen flutamide therapy these Nausea vomiting the most frequently observed adverse phosphate. While symptoms usually mild moderate nature, they may occasionally more troublesome patient necessitate withdrawal treatment. Cardiovascular complications serious, though less encountered, effect drug. However, avoided careful selection prophylactic measures. Unlike some other agents, rarely associated myelosuppression. addition producing established subjective status many shown reduce intensity pain improve performance Thus, valuable for cancer and, pending results future phase III trials, also play an important role part combination regimen (with such paclitaxel, vinblastine etoposide) phosphate) drug dual mode action. Estrone estradiol, products metabolism phosphate, antigonadotrophic activity resulting reduced testosterone those after surgical castration. Estramustine, cytotoxic metabolite produced dephosphorylation parent compound, undergoes further estromustine; both metabolites exert antimitotic essentially mediated depolymerisation. against human prostatic cell lines animal models. Combinations antimicrotubular topisomerase II inhibitor etoposide, synergistic activity. Approximately 75% absorbed oral administration. Thereafter, rapid presystemic (predominantly gastrointestinal tract) yield active which subsequently partially oxidised produce isomer, estromustine. Both undergo partial hydrolysis derivatives estrone respectively. The absorption markedly impaired calcium ions form insoluble salt should not administered concomitantly dairy products, calcium-rich foods drugs. elimination half-life relatively short (1.27 hours). estromustine much longer between 8.88 22.7 hours one study. excreted via biliary route. predominantly evaluated second-line option reported therapy. An analysis 634 disease who received revealed mean rate 37%. More recently, several investigated therapeutic efficacy combinations either using declining prostate-specific antigen (PSA) monitor response. Objective were higher improvements parameters greater than trials needed before apparent superiority regimens treatments can confirmed. relapsed following hormonal therapy, was streptozocin, had epirubicin, but medroxyprogesterone (although there difference progression-free groups). mitomycin appeared equally progressive disease; time progression 5 months median 10 groups. A cisplatin primary achieving various orally intramuscularly formulations flutamide. Patients localised (and >lymph node involvement) adjuvant definitive radiotherapy cyclophosphamide neoadjuvant 6 weeks radical prostatectomy resulted significantly lower incidence positive margins T2 tumours compared encountered nausea vomiting; generally severe require reduction dosage discontinuation (including ischaemic heart venous thromboembolism cardiac failure) 10% during first 20 25% To minimise risk complications, prophylaxis anticoagulants, aspirin (acetylsalicylic acid), diuretics advocated investigators. data suggest recipients experiencing cardiovascular Elevated serum transaminases, reversible upon As estrogens, experience gynaecomastia. recommended ranges 140 1400 mg/day 2 3 divided doses, 1 hour meals. Treatment initiated 560 1120 (in doses), adjustment according tolerability. consume calcium-containing drugs (e.g calcium-based antacids) doses Intravenous 300 450 maximum weeks. given 300mg dose twice week.