Eulexin scientific update |
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Int J Cancer. 2008 Feb 15;122(4):864-70.
Zhigang Z, Wenlu S.
Department of Urology, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong Province, China.
Flutamide reduced prostate cancer development and prostate stem cell antigen mRNA expression in high grade prostatic intraepithelial neoplasia.
High-grade prostatic intraepithelial neoplasia (HGPIN) appears to represent an ideal target for chemoprevention of prostate cancer (PCa). HGPIN responds to androgen ablation and has prostate stem cell antigen (PSCA) mRNA expression. One hundred and seventy two patients with isolated HGPIN were randomized in a double-blind manner to receive flutamide 250 mg/day (86 cases) or a placebo (86 cases) for 12 months and were rebiopsied at 12 and 60 months. PSCA mRNA expression was assessed in the prestudy and 12-month biopsies by in situ hybridization. The incidence of subsequent PCa was 11.6% in the flutamide group when compared with 30.2% in the placebo group over a follow-up period of 5 years (p = 0.0027). PSCA mRNA expression levels were significantly declined after treatment compared with that before treatment (p < 0.001). After treatment, 66 patients had reduced PSCA mRNA expression, in whom none was found with cancer on follow-up, however, 13 cases had increased PSCA mRNA expression levels, in whom 11 were found with cancer. Cox regression analysis demonstrated that HGPIN with increased PSCA mRNA expression after flutamide had an increased relative risk of 4.33 to develop subsequent cancer (95% confidence intervals: 2.48-7.36; p < 0.001). Seventeen (19.8%) cases had the flutamide-associated side effects, which were graded as mild, but all did not discontinue study. Flutamide can effectively and safely reduce PCa development and significantly suppress PSCA mRNA expression in men with isolated HGPIN, whereas the increased PSCA mRNA expression after therapy may be a clinically adverse predictor for cancer onset.
Fertil Steril. 2008 Mar 11.
Castelo-Branco C, Moyano D, Gómez O, Balasch J.
Institut Clinic of Gynecology, Obstetrics and Neonatology, Faculty of Medicine-University of Barcelona, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Long-term safety and tolerability of flutamide for the treatment of hirsutism.
OBJECTIVE: To evaluate the long-term safety and tolerability of flutamide therapy for hirsutism. DESIGN: Prospective observational study. SETTING: Gynecology department in a teaching hospital. PATIENT(S): Hyperandrogenic women presenting for hirsutism treatment were followed between January 2000 and January 2007. INTERVENTION(S): Women received flutamide 250 mg/day alone (n = 27) or combined with a fixed dose of an oral contraceptive containing 0.020 mg of ethinyl estradiol (EE) and 0.15 mg of desogestrel (n = 56). MAIN OUTCOME MEASURE(S): Adverse events, safety, tolerability and efficacy were assessed every 6 months during the follow-up. Liver and lipid profiles were also recorded. RESULT(S): Patients under flutamide therapy showed, compared with basal values, a significant progressive decrease in hirsutism scores after 6 months of treatment with a maximum effect at 12 months that was maintained during the 84 months of follow-up. A total of 40.96% women presented one or more adverse effects during the follow-up; 33.73% showed at least one adverse effect possibly related with the study drug, and 24.09% withdrew from the study because of adverse effects. During the follow-up, as many as 59% of patients abandoned the study. CONCLUSION(S): Flutamide is very effective for hirsutism treatment; however, adverse effects are very frequent and associated with low long-term compliance.
Adv Ther. 2008 Jul-Aug;25(4):321-8.
Karakurt F, Sahin I, Güler S, Demirbas B, Culha C, Serter R, Aral Y, Bavbek N.
Department of Endocrinology and Metabolic Diseases, Fatih University Faculty of Medicine, Isci Bloklari Mah 420. Sokak, 52/11 Yuzuncuyil, Ankara, Turkey.
Comparison of the clinical efficacy of flutamide and spironolactone plus ethinyloestradiol/cyproterone acetate in the treatment of hirsutism: A randomised controlled study.
Introduction: Hirsutism is commonly a consequence of ovarian androgen over-production. Polycystic ovary syndrome (PCOS) or peripheral hypersensitivity to normal androgen circulating levels (idiopathic hirsutism) can be the underlying cause. Several drugs with anti-androgenic properties, such as cyproterone acetate (CPA), spironolactone and flutamide have been used to treat hirsutism, but the efficacy of these drugs has yet to be fully elucidated. The objective of this study was to compare the effectiveness of flutamide, and spironolactone plus a combination tablet of 2 mg CPA/35 mug ethinyloestradiol (EE) in the treatment of hirsutism. Methods: A prospective randomised clinical study was conducted in a tertiary care hospital setting. Twenty-nine women with hirsutism as a consequence of PCOS or idiopathic hirsutism were randomly assigned to receive 250 mg/day flutamide alone or 100 mg/day spironolactone plus a combination tablet of 2 mg CPA/35 mug EE, for 6 months. Patients' hormonal and lipid profiles were evaluated. Hirsutism was graded according to the modified Ferriman-Gallwey (mF-G) score, and side effects were monitored. Results: A significant decrease in mF-G scores was observed in the flutamide (from 11.2+/-3.3 to 7.6+/-4.0) and spironolactone plus CPA/EE (from 9.9+/-1.9 to 7.1+/-2.0) groups. However, there was no statistically significant difference between the two groups. After flutamide therapy, total cholesterol levels decreased significantly but no significant change was observed in any other lipid parameters or in the patients' hormone profiles. After spironolactone plus CPA/EE therapy, levels of luteinising hormone, total testosterone and free testosterone significantly decreased and triglyceride levels increased. No patients were found to have abnormal liver function test results. Conclusion: Flutamide and spironolactone plus CPA/EE are effective drugs in the treatment of hirsutism.
J Appl Physiol. 2008 Aug;105(2):595-602. Epub 2008 Jun 5.
Kan WH, Hsieh CH, Schwacha MG, Choudhry MA, Raju R, Bland KI, Chaudry IH.
Center for Surgical Research, Department of Surgery, University of Alabama at Birmingham, G094 Volker Hall, 1670 Univ. Blvd., Birmingham, AL 35294-0019, USA.
Flutamide protects against trauma-hemorrhage-induced liver injury via attenuation of the inflammatory response, oxidative stress, and apopotosis.
Although studies have shown that administration of testosterone receptor antagonist, flutamide, following trauma-hemorrhage, improves hepatic, cardiovascular, and immune functions, the precise cellular/molecular mechanisms responsible for producing these salutary effects remain largely unknown. To study this, male C3H/HeN mice were subjected to a midline laparotomy and hemorrhagic shock (35+/-5 mmHg for approximately 90 min), followed by resuscitation with Ringer lactate. Flutamide (25 mg/kg) or vehicle was administered subcutaneously at the onset of resuscitation, and animals were killed 2 h thereafter. Hepatic injury was assessed by plasma alpha-glutathione S-transferase concentration, liver myeloperoxidase activity, and nitrotyrosine formation. Hepatic malondialdehyde and 4-hydroxyalkenals (lipid peroxidation indicators), cellular DNA fragmentation, and the expression of inducible nitric oxide synthase and hypoxia-inducible factor-1alpha were also evaluated. Cytokines (TNF-alpha, IL-6) and chemokines (keratinocyte-derived chemokine and monocyte chemoattractant protein-1) levels were determined by cytometric bead array. The results indicate that flutamide administration after trauma-hemorrhage reduced liver injury, which was associated with decreased levels of alpha-glutathione S-transferase, myeloperoxidase activity, nitrotyrosine formation, lipid peroxidation, and cytokines/chemokines (systemic, liver tissue, and intracellular cytokines/chemokines). Cellular apoptosis, hepatocyte hypoxia-inducible factor-1alpha, and inducible nitric oxide synthase expression were also decreased under such conditions. Thus administration of flutamide following trauma-hemorrhage protects against liver injury via reduced inflammation, cellular oxidative stress, and apoptosis.
Reprod Toxicol. 2008 Aug 13.
Anway MD, Rekow SS, Skinner MK.
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4234, United States.
Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis.
Exposure of gestating female rats to the anti-androgenic endocrine disruptor vinclozolin has been shown to induce transgenerational adult onset disease phenotypes. The current study, was designed to compare the actions of vinclozolin to the known anti-androgenic compound flutamide. The gestating female rats were exposed to intraperitoneal injections during embryonic day 8-14 (E8-E14) to 100mg/kg/day vinclozolin or flutamide at either 5mg or 20mg/kg/day. As previously observed, vinclozolin induced a transgenerational testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm number. In contrast, the flutamide exposures resulted in a testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm numbers in the F1 generation only, and not the F2 and F3 generation adult males. Interestingly, some of the low dose (5mg/kg) flutamide F2 generation offspring developed spinal agenesis and supernummery development (polymelia) of limbs. Although the actions of vinclozolin and flutamide appear similar in the F1 generation males, the transgenerational effects of vinclozolin do not appear to be acting through the same anti-androgenic mechanism as flutamide.
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Drug category:Anti-cancer drugs
 Eulexin scientific update
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