• Keywords
• TIBOLON,
• MeSH
• Breast Density drug effects   MeSH
• Drug Evaluation MeSH
• Hormone Replacement Therapy MeSH
• Climacteric * drug effects   MeSH
• Humans MeSH
• Estrogen Receptor Modulators * administration & dosage   therapeutic use   MeSH
• Osteoporosis drug therapy   MeSH
• Randomized Controlled Trials as Topic MeSH
• Check Tag
• Humans MeSH
• Female MeSH

Tibolon je zatím jediná terapeutická modalita plně srovnatelná s hormonální substituční terapií. Lepších výsledků dosahuje v oblasti ovlivnění psychiky a sexuality postmenopauzální ženy. Snižuje mamografickou denzitu. Z hlediska karcinomu prsu je srovnatelně bezpečný s estrogenní terapií a pravděpodobně bezpečnější než estrogen-gestagenní léčba. Tibolon by měl být primárně volen u postmenopauzálních žen s poruchami sexuality a nálady, s mastalgiemi a vysokou prsní denzitou.

Tibolon is the only therapeutic approach to climacteric symptoms, prevention of osteoporosis and urogenital atrophy with the same efficacy as hormone replacement therapy. Tibolon has more positive effects on sexuality and mood changes in menopausal women. It decreases the mammographic density. Its safety for breast cancer is the same as for only estrogen therapy and better than for estrogen-gestagen therapy. Tibolon is the first choice for postmenopausal women with mood and sexuality disorders, women with mastodynia and high mammographic density.

• Keywords
• TIBOLON,
• MeSH
• Breast Density drug effects   MeSH
• Drug Evaluation MeSH
• Hormone Replacement Therapy MeSH
• Climacteric drug effects   MeSH
• Humans MeSH
• Estrogen Receptor Modulators * administration & dosage   therapeutic use   MeSH
• Breast Neoplasms MeSH
• Osteoporosis drug therapy   MeSH
• Randomized Controlled Trials as Topic MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Review MeSH

Karcinom prsu je velmi heterogenní onemocnění, jeho léčba je diferencována na základě fenotypu. V poslední době se zlepšila zejména prognóza nemocných s HER2-pozitivním onemocněním. Nově je možné podávat monoklonální protilátku pertuzumab, subkutánní trastuzumab a brzy by měla být schválena úhrada trastuzumab emtansinu. V hormonální terapii se používá vzhledem k prokázané vyšší účinnosti vysokodávkovaný fulvestrant a připravuje se stanovení úhrady pro everolimus v kombinaci s exemestanem v léčbě hormonálně dependentního diseminovaného onemocnění po progresi při léčbě nesteroidním inhibitorem aromatázy. V konvenční chemoterapii metastatického onemocnění předléčeného taxany, antracykliny a kapecitabinem je do praxe nově uveden eribulin.

Breast cancer is a heterogeneous disease; its therapy is differentiated on the basis ofphenotype. Recently, the prognosis of patients especially with HER2-positive disease has improved. It is possible to use the new monoclonal antibody pertuzumab, subcutaneously administered trastuzumab and soon reimbursement of trastuzumab-emtansin should be approved. High dose fulvestrant is used in hormone therapy due to proven efficacy. Preparations for determining the reimbursement are in progress for everolimus in combination with exemestane for the treatment of hormone-dependent metastatic breast cancer after progression while treated with non-steroidal aromatase inhibitor. Eribulin is now available for the treatment of metastatic breast cancer pretreated with taxanes, anthracyclines and capecitabine.

• MeSH
• Estrogen Antagonists administration & dosage   pharmacokinetics   adverse effects   therapeutic use   MeSH
• Anthracyclines therapeutic use   MeSH
• Molecular Targeted Therapy MeSH
• Adult MeSH
• Estradiol analogs & derivatives   MeSH
• Phenotype MeSH
• Antineoplastic Agents, Hormonal administration & dosage   pharmacokinetics   adverse effects   therapeutic use   MeSH
• Hormone Replacement Therapy MeSH
• Antibodies, Monoclonal, Humanized administration & dosage   pharmacokinetics   adverse effects   therapeutic use   MeSH
• Aromatase Inhibitors administration & dosage   pharmacokinetics   adverse effects   therapeutic use   MeSH
• Carcinoma drug therapy   MeSH
• Humans MeSH
• Maytansine analogs & derivatives   administration & dosage   pharmacokinetics   adverse effects   therapeutic use   MeSH
• Microtubules drug effects   MeSH
• Adolescent MeSH
• Estrogen Receptor Modulators administration & dosage   pharmacokinetics   adverse effects   therapeutic use   MeSH
• Tubulin Modulators administration & dosage   pharmacokinetics   adverse effects   therapeutic use   MeSH
• Drug Monitoring MeSH
• Breast Neoplasms * drug therapy   MeSH
• Prodrugs MeSH
• Prognosis MeSH
• Antimetabolites, Antineoplastic therapeutic use   MeSH
• Receptor, ErbB-2 antagonists & inhibitors   MeSH
• Aged MeSH
• Sirolimus analogs & derivatives   administration & dosage   pharmacokinetics   adverse effects   therapeutic use   MeSH
• Taxoids therapeutic use   MeSH
• Therapeutic Equivalency MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: At the time of the initial analysis of overall survival (OS) for the Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) randomized, double-blind, phase III trial, approximately 50% of patients had died. A final analysis of OS was subsequently planned for when 75% of patients had died. METHODS: Patients were randomly assigned 1:1 to fulvestrant 500 mg administered as two 5-mL intramuscular injections on days 0, 14, and 28 and every 28 (±3) days thereafter or fulvestrant 250 mg administered as two 5-mL intramuscular injections (one fulvestrant and one placebo [identical in appearance to study drug]) on days 0, 14 (two placebo injections only), and 28 and every 28 (±3) days thereafter. OS was analyzed using an unadjusted log-rank test. No adjustments were made for multiplicity. Serious adverse events (SAEs) and best response to subsequent therapy were also reported. All statistical tests were two-sided. RESULTS: In total, 736 women (median age = 61.0 years) were randomly assigned to fulvestrant 500 mg (n = 362) or 250 mg (n = 374). At the final survival analysis, 554 of 736 (75.3%) patients had died. Median OS was 26.4 months for fulvestrant 500 mg and 22.3 months for 250 mg (hazard ratio = 0.81; 95% confidence interval = 0.69-0.96; nominal P = .02). There were no clinically important differences in SAE profiles between the treatment groups; no clustering of SAEs could be detected in either treatment group. Type of first subsequent therapy and objective responses to first subsequent therapy were well balanced between the two treatment groups. CONCLUSIONS: In patients with locally advanced or metastatic estrogen receptor-positive breast cancer, fulvestrant 500 mg is associated with a 19% reduction in risk of death and a 4.1-month difference in median OS compared with fulvestrant 250 mg. Fulvestrant 500 mg was well tolerated, and no new safety concerns were identified.

• MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Estradiol administration & dosage   analogs & derivatives   MeSH
• Antineoplastic Agents, Hormonal administration & dosage   MeSH
• Injections, Intramuscular MeSH
• Kaplan-Meier Estimate MeSH
• Middle Aged MeSH
• Humans MeSH
• Estrogen Receptor Modulators administration & dosage   MeSH
• Breast Neoplasms drug therapy   metabolism   mortality   pathology   MeSH
• Odds Ratio MeSH
• Disease-Free Survival MeSH
• Receptors, Estrogen metabolism   MeSH
• Drug Administration Schedule MeSH
• Aged MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

• MeSH
• Androstadienes therapeutic use   MeSH
• Aromatase Inhibitors administration & dosage   MeSH
• Clinical Trials as Topic MeSH
• Drug Therapy, Combination methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Metastasis * drug therapy   MeSH
• Estrogen Receptor Modulators administration & dosage   MeSH
• Breast Neoplasms * drug therapy   genetics   pathology   MeSH
• Neoplasms, Hormone-Dependent * drug therapy   MeSH
• Drug-Related Side Effects and Adverse Reactions epidemiology   etiology   MeSH
• Disease-Free Survival MeSH
• Receptor, ErbB-2 drug effects   MeSH
• Receptors, Estrogen drug effects   MeSH
• Sirolimus analogs & derivatives   therapeutic use   MeSH
• Tamoxifen therapeutic use   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Comment MeSH

• Keywords
• Pertuzumab, Trastuzumab-DM1, Eribulin,
• MeSH
• Estradiol analogs & derivatives   pharmacology   therapeutic use   MeSH
• Everolimus MeSH
• Fulvestrant MeSH
• Furans administration & dosage   pharmacology   therapeutic use   MeSH
• Genes, erbB-2 genetics   MeSH
• Ketones administration & dosage   pharmacology   therapeutic use   MeSH
• Humans MeSH
• Estrogen Receptor Modulators administration & dosage   pharmacology   therapeutic use   MeSH
• Antibodies, Monoclonal administration & dosage   pharmacology   therapeutic use   MeSH
• Breast Neoplasms * drug therapy   therapy   MeSH
• Antineoplastic Agents administration & dosage   pharmacology   therapeutic use   MeSH
• Randomized Controlled Trials as Topic MeSH
• Sirolimus administration & dosage   pharmacology   therapeutic use   MeSH
• Check Tag
• Humans MeSH

Článek podává přehled o léčivech pro antiresorpční léčbu postmenopauzální osteoporózy. Jsou uvedeny hlavní indikace, dlouhodobá účinnost a nežádoucí účinky léčiv. Složení a mikrostruktura kosti se mění v závislosti na stupni útlumu remodelace a modelace kostní hmoty. Volba léčiva by se měla odvíjet nejenom od změn denzity kostního minerálu (BMD) a poklesu relativního rizika zlomenin v registračních studiích, ale také od dlouhodobého účinku léčiva na kvalitu kostní hmoty. Osteoporóza je chronické onemocnění. Po pěti letech užívání aminobisfosfonátů má být zvážena vhodnost pokračování této léčby. Dostatečně dokumentované studie rizika zlomenin po ukončení léčby zatím chybějí.

This review examines currently available clinical data on the pharmacological properties of antiresorptive treatments for postmenopausal osteoporosis, their indications, long-term anti-fracture efficacy and side-effects. The composition and microstructure of bone alters according to the degree of suppression of bone remodelling and modelling. The choice of an adequate treatment should be made not only in light of increased bone mineral density (BMD) and reduction of relative risk of fracture in pivotal clinical trials, but also in light of the long-term ability of the given drug to maintain bone tissue quality. Osteoporosis is a chronic condition. The appropriateness of continuing treatment with aminobisphosphonates after 5 years should be considered. Adequately powered post-discontinuation studies on maintenance or loss of fracture benefit are lacking.

• MeSH
• Alendronate analogs & derivatives   administration & dosage   pharmacology   MeSH
• Bisphosphonate-Associated Osteonecrosis of the Jaw epidemiology   MeSH
• Diphosphonates * pharmacology   adverse effects   therapeutic use   MeSH
• Estrogen Replacement Therapy * methods   MeSH
• Risk Assessment MeSH
• Imidazoles administration & dosage   pharmacology   adverse effects   MeSH
• Etidronic Acid analogs & derivatives   administration & dosage   pharmacology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Estrogen Receptor Modulators * administration & dosage   pharmacology   adverse effects   MeSH
• Norpregnenes administration & dosage   pharmacology   MeSH
• Organometallic Compounds * administration & dosage   pharmacology   adverse effects   MeSH
• Osteoporotic Fractures * epidemiology   etiology   prevention & control   MeSH
• Osteoporosis, Postmenopausal * diagnosis   drug therapy   MeSH
• Acute-Phase Reaction epidemiology   chemically induced   MeSH
• Bone Resorption * etiology   drug therapy   MeSH
• Fractures, Stress epidemiology   chemically induced   MeSH
• Thiophenes administration & dosage   pharmacology   adverse effects   MeSH
• Calcium administration & dosage   MeSH
• Vitamin D administration & dosage   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Přibližně 75 % karcinomů prsu exprimuje estrogenové nebo progesteronové receptory. Hormonální léčba patří mezi základní léčebné postupy u nemocných s metastatickým karcinomem prsu. Představitelem downregulátorů estrogenových receptorů je fulvestrant. Dosud byl podáván v dávce 250 mg jednou za 28 dní. Recentní klinická studie FIRST prokázala, že pacientky léčené v 1. linii metastatického karcinomu prsu vyšší dávkou fulvestrantu 500 mg jednou za 28 dní měly signifikantně delší dobu do progrese nemocnění než pacientky léčené anastrozolem. Klinická studie CONFIRM potvrdila lepší účinnost fulvestrantu ve vyšším dávkování. Pacientky léčené ve druhé linii fulvestrantem ve vyšší dávce měly signifikantně delší dobu do progrese onemocnění než pacientky léčené dávkou nižší. Ve světle těchto výsledků se fulvestrant v dávkování 500 mg jednou za 28 dní stal standardní léčbou.

Either estrogen or progesterone receptors are expressed by about 75% of breast cancers. Endocrine therapy is one of the principal treatment options in patients with metastatic disease. Fulvestrant represents a down- -regulator of estrogen receptors. It has been given in a dose of 250 mg once every 28 days. The recent clinical trial FIRST demonstrated that patients with metastatic breast cancer treated in the first line by a higher 500 mg dose of fulvestrant achieved significantly better time to disease progression than patients treated with anastrozole. The improved efficacy of fulvestrant given in higher doses was also shown in the clinical trial CONFIRM. Patients undergoing second-line treatment with the higher dose of fulvestrant achieved significantly longer time to disease progression than those treated with the lower dose. In the light of these results, fulvestrant 500 mg-once-every-28 days dosing became a standard treatment.

• Keywords
• karcinom prsu, hormonální léčba,
• MeSH
• Estradiol administration & dosage   MeSH
• Clinical Trials, Phase III as Topic MeSH
• Humans MeSH
• Neoplasm Metastasis drug therapy   MeSH
• Estrogen Receptor Modulators administration & dosage   MeSH
• Breast Neoplasms drug therapy   MeSH
• Check Tag
• Humans MeSH
• Female MeSH

• MeSH
• Double-Blind Method MeSH
• Middle Aged MeSH
• Humans MeSH
• Estrogen Receptor Modulators administration & dosage   MeSH
• Breast Neoplasms drug therapy   pathology   MeSH
• Hot Flashes drug therapy   MeSH
• Norpregnenes administration & dosage   MeSH
• Placebos therapeutic use   MeSH
• Postmenopause MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Randomized Controlled Trial MeSH

• MeSH
• Estrogens administration & dosage   metabolism   therapeutic use   MeSH
• Fulvestrant MeSH
• Hormones therapeutic use   MeSH
• Aromatase Inhibitors administration & dosage   adverse effects   therapeutic use   MeSH
• Humans MeSH
• Estrogen Receptor Modulators administration & dosage   metabolism   therapeutic use   MeSH
• Breast Neoplasms drug therapy   therapy   MeSH
• Postmenopause metabolism   drug effects   MeSH
• Tamoxifen administration & dosage   adverse effects   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Practice Guideline MeSH