Background:
Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonists is well established for the treatment of men with metastatic prostate cancer. As clear ...differences in efficacy, safety, or tolerability between the available LHRH agonists are lacking, the healthcare management team needs to look to practical differences between the formulations when selecting therapy for their patients. Moreover, as the economic burden of prostate cancer rises alongside earlier diagnosis and improved survival, the possibility for cost savings by using products with specific features is growing in importance.
Methods:
A review was conducted to summarize the information on the different LHRH agonist formulations currently available and offer insight into their relative benefits and disadvantages from the perspectives of physicians, a pharmacist, and a nurse.
Results:
The leuprorelin acetate and goserelin acetate solid implants have the advantage of being ready to use with no requirement for refrigeration, whereas powder and microsphere formulations have to be reconstituted and have specific storage or handling constraints. The single-step administration of solid implants, therefore, has potential to reduce labor time and associated costs. Dosing frequency is another key consideration, as administering the injection provides an opportunity for face-to-face interaction between the patient and healthcare professionals to ensure therapy is optimized and give reassurance to patients. Prostate cancer patients are reported to prefer 3- or 6-monthly dosing, which aligns with the monitoring frequency recommended in European Association of Urology guidelines and has been shown to result in reduced annual costs compared with 1-month formulations.
Conclusions:
A number of practical differences exist between the different LHRH agonist preparations available, which may impact on clinical practice. It is important for healthcare providers to be aware and carefully consider these differences when selecting treatments for their prostate cancer patients.
Background:
There are two slow-release ready-to-use forms of leuprorelin acetate (1-month and 3-month) that are available as solid, biodegradable implants for the treatment of advanced, ...hormone-sensitive prostate cancer. These implants have been shown to be as effective as traditional leuprorelin acetate microspheres for achieving successful testosterone suppression (⩽0.5 ng/ml) and lowering prostate-specific antigen (PSA) levels. Here we further evaluate testosterone suppression levels from four clinical trials evaluating the 3-month leuprorelin implant, including analysis below the European Association of Urology (EAU) castration level (<0.2 ng/ml).
Methods:
Studies were conducted in patients with locally advanced/metastatic prostate cancer: (1) a randomised, controlled single-dose study comparing the leuprorelin implant with leuprorelin microspheres; (2) a single-arm, single-dose study of the leuprorelin implant; (3 and 4) two long-term studies with the leuprorelin implant administered twice, 12 or 16 weeks apart. Patients received 3-month leuprorelin (5 mg) implant or 3-month leuprorelin (10.72 mg) microspheres. Testosterone levels were analysed using radioimmunoassay or ultrasensitive liquid chromatography tandem mass spectrometry.
Results:
Both the leuprorelin implant and the leuprorelin microspheres achieved mean testosterone suppression (⩽0.5 ng/ml) within 4 weeks for >3 months. In both long-term, single-arm studies with the leuprorelin implant, median values of testosterone ⩽0.2 ng/ml were achieved at Week 4 and maintained until study completion (6 and 8 months); PSA decrease was also observed versus baseline.
Conclusions:
Long-lasting steady serum levels of testosterone, comparable with orchiectomy and consistent with the EAU-recommended castration level (<0.2 ng/ml), were achieved at Week 4 and maintained up to 8 months in men with advanced prostate cancer who received the leuprorelin implant.
Adenokarcinom prostate najčešća je zloćudna neoplazma u muškaraca u Republici Hrvatskoj. Klinički je često asimptomatski, a najčešće se otkriva na osnovi povišenih vrijednosti PSA u serumu. Odluka o ...liječenju
donosi se na temelju TNM-klasifikacije, gradusne skupine i vrijednosti PSA. Klinički lokalizirana bolest vrlo se uspješno liječi radikalnom prostatektomijom ili radikalnom radioterapijom s hormonskom terapijom ili bez nje. Klinički lokalno uznapredovala bolest najčešće se liječi združenom primjenom radikalne radioterapije i hormonske
terapije. Metastatska bolest godinama se može kontrolirati androgenom deprivacijom, a nakon razvoja kastracijski rezistentne bolesti opravdani su kemoterapija ili dodatni oblici hormonske terapije. U radu su prikazane kliničke upute radi ujednačenja postupaka i kriterija postavljanja dijagnoze, liječenja i praćenja bolesnika s rakom prostate u Republici Hrvatskoj.
Značajan napredak u ranom otkrivanju i kvalitetnije liječenje oboljelih rezultirali su činjenicom da u najrazvijenijim zemljama gotovo 90% žena s dijagnozom raka dojke preživi duže od 5 godina nakon ...dijagnoze i liječenja. Kod jedne od dvadeset žena oboljelih od raka dojke unutar 10 godina od postavljanja dijagnoze razvit će se novi primarni tumor čije sijelo nije dojka. Mutacije gena BRCA 1 i 2, RAD51C, MMR, p53, CDKN2A te 113insArg povezuju se s povećanim rizikom od razvoja raka dojke i drugih zloćudnih tumora. Čini se da i modalitet liječenja utječe na povećanje rizika od razvoja novoga zloćudnog tumora. Tako je nakon radioterapije primijećen povećan rizik za tkiva koja primaju višu dozu zračenja, osobito kod mlađih bolesnica, desetak godina nakon zračenja. Nađena je povećana incidencija leukemije i mijelodisplastičnog sindroma nakon liječenja kemoterapijom u odnosu na opću populaciju, ali smanjen rizik od razvoja zloćudnih tumora ostalih sijela. Odranije poznat povećan rizik od razvoja raka endometrija nakon hormonske terapije tamoksifenom potvrđen je i u novijim studijama. Mehanizam nastanka novih primarnih zloćudnih tumora nije potpuno razjašnjen. Koliki udio u tome imaju zajednički nasljedni čimbenici, mogući zajednički okolišni rizični čimbenici ili neželjene nuspojave specifičnog onkološkog liječenja tek se treba otkriti.
Significant advances in early breast cancer detection and increased quality of care within developed countries resulted in longer than five years survival in almost 90% of women diagnosed and treated ...for breast cancer. One in twenty women diagnosed with breast cancer will develop a new primary non-breast malignancy within 10 years from initial diagnosis. Mutations in BRCA 1 i 2, RAD51C, MMR, p53, CDKN2A and 113insArg genes are linked with increased risk of breast cancer and other cancer sites. It seems that treatment modalities also play significant role in development of new primary malignancies. Tissues that receive higher doses of radiation during radiotherapy of breast cancer are under increased risk of developing new primary tumor, especially in younger women, ten years after the treatment. Chemotherapy may cause higher incidence of leukemia and myelodysplastic syndrome but lower overall risk for development of other malignancies. Connection between tamoxifen therapy and increased risk of endometrial cancer is well known and confirmed also in recent studies. The true mechanism of cancer development is still unclear. Significance of hereditary factors, possible common environmental risk factors or unwanted side effects of the specific anticancer treatments are yet to be discovered.
The strategy for treating prostate cancer patients depends on the assessment of disease extent, assessment of the risk of disease relapse, assessment of life expectancy, comorbidities, affinities and ...life-style. Since the activity and survival of prostate cancer cells is at least initially dependent on androgen stimulation, hormonal therapy is one of the several standard treatment modalities. Hormonal therapy is aimed at decreasing this androgen stimulation either by lowering androgen production or by blocking receptor binding. Hormonal therapy is in fact androgen-suppressive therapy (AST) or androgen-deprivation therapy (ADT). If effective, it results in the lack of cancer cell stimulation, thus causing their apoptosis and consequently decline in tumor growth and size. Hormonal therapy is used as a first-line treatment modality for metastatic disease. In addition to this indication, hormonal therapy is also used as an adjunct to radiotherapy with curative intent for patients with non-metastic disease but having an intermediate and high risk of disease relapse. In combination with radiotherapy, hormonal therapy can be applied before, concomitantly and after radiotherapy for the duration of 6 months or 2 to 3 years depending on the risk estimation. Regarding hormonal therapy, it can be applied in combination with other treatments, in several ways, and sometimes there might be several options available. This possible lack of a specific recommendation is a consequence of the fact that there is a limited number of adequate clinical studies which, moreover, may have yielded inconsistent results sometimes simply due to the patients' heterogeneity. Moreover, thanks to the newer and better diagnostic methods enabling the discovery of prostate cancer in earlier disease stages, as well as to the more effective treatments, there is also a prolongation of relapse-free survival and possibly of overall survival in patients having metastic disease. Consequently, the results of earlier clinical studies might no longer be applicable to the new "generations" of upcoming patients. As regards this improved survival, issues of patient's quality of life and possible side-effects of hormonal therapy are also becoming increasingly relevant because hormonal adverse events are time-dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, this paper aims to give an overview of the more recent findings, indications and observations regarding hormonal therapy.
Testicular tumors are the most common solid tumors in men between 15 and 34 years of age. The worldwide incidence of these tumors has doubled in the past 40 years. Germ cell tumors comprise 95% of ...malignant tumors arising in the testes and they are classified either as seminoma or nonseminoma. Testicular cancers have a high cure rates even in disseminated stage of the disease. The chemotherapy mostly contributed to these results but surgery is an inevitable part of successful treatment. In a significant number of these patients treatment algorithms with minimum side effects are designed with the intention to maintain same cure rates as previously used, more aggressive therapy. The following text presents the clinical guidelines in order to standardize the procedures and criteria for diagnosis, management, treatment and follow-up of patients with testicular cancer in Republic of Croatia.
Prostate adenocarcinoma is the second most common solid neoplasm in male population in Croatia. It rarely causes symptoms unless it is advanced. The finding of PSA rise is the most common reason for ...diagnostic workout. Treatment plan is based on TNM classification, Gleason score and PSA. Clinically localized disease is successfully treated by radical prostatectomy or radiotherapy with or without hormonal therapy. Locally advanced disease is treated with radiotherapy and hormonal therapy. Metastatic disease can be controlled for many years by androgen deprivation. For castration resistant disease appropriate treatment is chemotherapy or secondary hormonal therapy. The following paper presents the clinical guidelines in order to standardize procedures and criteria for the diagnosis, management, management, treatment and monitoring of patients with prostate cancer in the Republic of Croatia.
Strategija liječenja bolesnika s adenokarcinomom prostate ovisi o procjeni proširenosti bolesti, procjeni rizika od povratka bolesti, dobi, očekivanom trajanju života, komorbiditetima, afinitetima i ...načinu života. Jedan od standardnih terapijskih modaliteta jest i hormonska terapija. Hormonska terapija raka prostate zapravo je terapija koja suprimira androgen (AST) ili koja terapija deprivira androgen (ADT). Njezinom primjenom dolazi do sniženja razine androgena u krvi, a kako su stanice adenokarcinoma najvećim dijelom (³80%) hormonski ovisne o androgenima, prestanak stimulacije stanica raka androgenima dovodi do njihove apoptoze, usporava se rast tumora i smanjuje se njegova veličina. Stoga se ta vrsta terapije rabi u liječenju karcinoma prostate. Hormonska terapija indicirana je kao prvi terapijski modalitet kod nalaza metastatske bolesti. U slučaju primjene radioterapije na prostatu zahvaćenu rakom s kurativnom namjerom (kod nemetastatske bolesti) preporučuje se primjena terapije koja deprivira androgen u bolesnika sa srednjim i visokim rizikom od povratka bolesti prije, za vrijeme i poslije radioterapije u trajanju od 6 mjeseci ili 2–3 godine ovisno o procijenjenom riziku od povratka bolesti. U vezi s primjenom terapije koja deprivira androgen, a koja se može primijeniti na više načina i u više kombinacija, za određene kliničke situacije ne postoje konačne preporuke. Razloga je više: premalen broj odgovarajućih kliničkih studija, heterogenost bolesnika u studijama što otežava interpretaciju podataka te nekonzistentni rezultati. Također, kako novije dijagnostičke metode i postupci omogućavaju ranije otkrivanje raka prostate, a ranije i sve uspješnije liječenje produžava život bolesnika s metastatskom bolešću, rezultati »ranijih« kliničkih studija mogu gubiti na aktualnosti. Isto tako, sa sve dužim preživljenjem bolesnika sve važnija postaje kvaliteta života, odnosno nuspojave liječenja, kao i procjena koristi u odnosu prema štetnosti same terapije. Cilj je prikaza da upozori na novije spoznaje, kao i na moguće dileme o mjestu i primjeni terapije koja deprivira androgen.
Urothelial cancer is the most common bladder cancer. Hematuria is the most common presenting symptom in patients with bladder cancer. The most common diagnostics of bladder cancer is performed by ...transurethral resection of bladder after which pathohistological diagnosis is set. It is necessary to determine whether the cancer penetrated in muscle layer (muscle-invasive cancer) or not (muscle-noninvasive cancer). Decision on therapeutic modality depends on the clinical stage of disease and on prognostic and risk factors. For muscle non-invasive bladder cancer transurethral resection is preferred with or without intravesical instillation of Bacillus Calmette-Guérin (BCG). For invasive cancer the method of choice is radical cystectomy. Radiotherapy is used in radical and palliative purposes. Metastatic disease is most frequently treated by chemotherapy metotrexate/vinblastine/doxorubicine/cisplatin (MVAC) or gemcitabine/cisplatin (GC). The purpose of this article is to present clinical recommendations to set standards of procedures and criteria in diagnostics, treatment and follow up of patients with bladder cancer in the Republic of Croatia.
PDF
