Bisfosfonati u liječenju koštanih metastaza

Bisphosphonates (BPs) are drugs that prevent bone loss in the bones affected by malignant disease. Bone homeostasis is maintained by the activity of osteoblasts and osteoclasts. It is generally accepted that activation of osteoclasts is a key step in the emergence and development of bone metastases, and that bone resorption is important not only in classical lithic lesions but also in osteoblastic bone metastases. BPs inhibit osteoclast activity and stimulate osteoclast apoptosis. Thus, osteoclasts are a key therapeutic target in the treatment of bone metastases. Therefore, the use of BPs is a standard form of treatment and prevention of complications associated with bone metastases in patients with malignant tumors, regardless of the primary. The greatest experience in the treatment of bone metastases from breast cancer is by intravenous BPs such as zolendronic acid, pamidronate and ibandronat. All of them show clinical activity. Until recently, randomized, placebo-controlled studies with BPs did not show a significant reduction in skeletal complications of bone metastases of prostate cancer. However, in the treatment of advanced hormone-resistant prostate cancer, zolendronic acid showed a reduction in the overall risk of skeletal complications by 36% and reduced the intensity of pain. The use of BPs in the treatment of bone metastases of other solid tumors has not been confirmed by randomized placebo-controlled studies. One study has shown a reduction in the incidence of bone metastases and their complications by about 30%. Patients with other tumors and symptomatic bone metastases may also be candidates for treatment with zolendronic acid, especially if bone metastases are a dominant site of metastasis and, if the expected survival is longer than 6 months. Patients with bone metastases of kidney cancer have a special benefit from BP therapy. Despite the apparent clinical benefit from the use of BPs, it is clear that they only play a part in preventing bone metastases and their complications, and some patients in spite of bone metastases never develop complications. Nowadays, one cannot predict which patients will benefit from BPs. Criteria are needed to define when BPs should be started and when they should be stopped. Before the administration of BPs, a primary disease, the extent of bone disease, expected survival, the probability that a patient would experience complications related to bone metastases should be taken into consideration.Bisfosfonati (BPs) su lijekovi koji sprječavaju gubitak koštane mase u kostima zahvaćenim zloćudnom bolešću. Koštanu homeostazu održava aktivnost osteoblasta i osteoklasta. Opće je prihvaćeno da je aktivacija osteoklasta ključni korak za pojavu i razvoj koštanih metastaza te da je resorpcija kosti važna ne samo kod klasičnih litičnih lezija nego i kod osteoblastičnih koštanih metastaza. Bisfosfonati priječe aktivnost i potiču apoptozu osteoklasta. Dakle, osteoklasti su glavna terapijska meta u liječenju koštanih metastaza. Primjena bisfosfonata standardni je oblik liječenja i prevencije komplikacija povezanih s koštanim metastazama u bolesnika sa zloćudnim tumorima bez obzira na primarno sijelo. Najviše iskustva u liječenju koštanih metastaza raka dojke stečeno je pri intravenskoj primjeni bisfosfonata i to zolendronične kiseline, pamidronata i ibandronata. Svi oni pokazuju kliničku aktivnost. Randomizirana, placebom kontrolirana klinička ispitivanja bisfosfonata donedavno nisu upućivala na značajnije smanjenje komplikacija prouzročenih koštanim metastazama raka prostate. Međutim, u liječenju uznapredovanog raka prostate otpornog na hormone pokazalo se da zolendronična kiselina smanjuje i ukupan rizik komplikacija u kostima za 36% i jačinu boli. Korist primjene bisfosfonata u liječenju koštanih metastaza drugih solidnih tumora nije potvrđena u randomiziranim, placebom kontroliranim ispitivanjima. U jednom je ispitivanju uočeno smanjenje pojavnosti koštanih metastaza i komplikacija za otprilike 30%. U bolesnika s drugim tumorima i simptomatičnim koštanim metastazama također bi se moglo primijeniti liječenje zolendroničnom kiselinom, osobito ako su koštane metastaze dominantno sijelo metastaza te ako je očekivano preživljenje dulje od 6 mjeseci. Bolesnicima s koštanim metastazama raka bubrega terapija bisfosfonatima je od posebne koristi. Unatoč očitoj kliničkoj koristi od primjene bisfosfonata, jasno je da oni samo sudjeluju u sprečavanju pojave koštanih metastaza i komplikacija izazvanih koštanim metastazama, a u nekih bolesnika komplikacije nikad me nastupe bez obzira na prisutnost koštanih metastaza. U ovom trenutku nije moguće predvidjeti koji će bolesnici imati koristi od bisfosfonata. Potrebno je utvrditi kriterije prema kojima bi se odredilo kad treba započeti i kad prekinuti primjenu bisfosfonata. Prije primjene bisfosfonata valja uzeti u obzir primarnu bolest, raširenost bolesti u kostima, očekivano preživljenje i vjerojatnost da bi bolesnik mogao imati komplikacije u vezi s koštanim metastazama

Tko bi trebao primiti novu hormonsku terapiju s terapijom smanjenja androgena u metastatskom hormon osjetljivom raku prostate?

Treatment with androgen deprivation (ADT ) has for many years been a standard treatment for patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, several phase 3 randomized trials have completely changed the therapeutic approach for these patients. First, two phase 3 trials, CHAARTED and STAMPEDE , showed that docetaxel added to ADT improves survival of patients with mHSPC. Here we present an overview of the most important trials in this setting: STAMPEDE , LATITUDE , ARCHE S, EN ZAMET and TIT AN in which abiraterone acetate, enzalutamide and apalutamide combined with ADT achieved significant improvement in overall survival of patients with mHSPC compared with ADT only. All three agents combined with ADT became new standard of therapy for this group of patients.Liječenje deprivacijom androgena (ADT ) već dugi niz godina je standardni oblik liječenja bolesnika s metastatskim hormonski osjetljivim rakom prostate (mHSPC). No, nekoliko studija faze 3 potpuno je promijenilo terapijski pristup za ove bolesnike. Najprije su dvije studije faze 3, CHAARTED i STAMPEDE , pokazale da dodatak docetaksela ADT poboljšava preživljenje bolesnika s mHSPC. Ovdje predstavljamo pregled najvažnijih ispitivanja u ovoj indikaciji: STAMPEDE , LATITUDE , ARCHE S, EN ZAMET i TIT AN u kojima su abirateron acetat, enzalutamid i apalutamid u kombinaciji s ADT-om postigli značajno poboljšanje ukupnog preživljavanja bolesnika s mHSPC-om u usporedbi samo s ADT-om. Dakle, sva tri lijeka u kombinaciji s ADT-om postali su novi standard terapije za ovu skupinu bolesnika

Trojna sustavna terapija za metastatski hormon-osjetljivi rak prostate

For many years, androgen deprivation therapy (ADT) as monotherapy has been the gold standard for metastatic hormone-sensitive prostate cancer (mHSPC) treatment. Several studies have been published within the last decade demonstrating a significant survival advantage resulting from combining the treatment with standard ADT plus docetaxel or androgen receptor targeted therapy (ARTA) compared to ADT monotherapy. Recently published data of the PEACE-1 and ARASENS trials suggest that in the future, triple therapy might be a treatment option for patients with mHSPC.Dugi niz godina, terapija deprivacije androgena (ADT) kao monoterapija bila je zlatni standard liječenja metastatskog hormonski osjetljivog raka prostate (mHSPC). U posljednjem desetljeću objavljeno je nekoliko studija koje pokazuju značajnu prednost u preživljavanju kombiniranim liječenjem ADT uz docetaksel ili terapijom koja cilja androgeni receptor (ARTA) u usporedbi s ADT u monoterapiji. Nedavno objavljeni podaci ispitivanja PEACE-1 i ARASENS sugeriraju da bi u budućnosti trostruka terapija mogla biti opcija liječenja pacijenata s mHSPC

Ovarian Cancer

Karcinom jajnika glavni je uzrok smrtnosti među karcinomima ženskoga spolnog sustava. Ne postoje rutinski testovi rane dijagnostike raka jajnika, a rano prepoznavanje bolesti otežano je zbog oskudne simptomatologije. Ukupna stopa preživljenja bolesnica od karcinoma jajnika iznosi gotovo 50%, što je velik napredak u odnosu na rane 80-e godine kada je iznosila oko 35%, a može se zahvaliti uvođenju paklitaksela u liječenje.Ovarian cancer is the main reason of death among gynecological cancers. There is no routine test for early diagnosis of ovarian cancer and early detection of this cancer is difficult because of lack of simptomatology. Overall survival rate among patients with ovarian cancer is almost 50 % and it represents a significant increase of survival in the last decade due the introduction of paclitaxel in the treatment of advanced stages of ovarian carcinoma

Clinical guidelines for diagnostics, treatment and monitoring of patients with testicular cancer

Rak testisa najčešći je solidni tumor u muškaraca u dobi od 15. do 34. godine. Incidencija raka testisa u svijetu udvostručena je u posljednjih 40 godina. Tumori zametnih stanica čine 95% svih tumora testisa, a podijeljeni su u dva osnovna histološka tipa: seminomi i neseminomi. Osobito značenje daje im velik postotak izlječivosti i u diseminiranoj fazi bolesti. Tom je uspjehu najviše pridonijela kemoterapija, ali kirurgija je i dalje neizostavan dio uspješnog liječenja. U znatnog dijela bolesnika danas se nastoji odrediti terapijski minimum kojim se izbjegava niz nuspojava, a dovodi do jednakog uspjeha kao i donedavno agresivniji terapijski pristup. U tekstu koji slijedi iznesene su kliničke upute radi standardizacije dijagnostike, liječenja i praćenja bolesnika s tumorima zametnih stanica testisa u Republici Hrvatskoj.Testicular tumors are the most common solid tumors in men between age 15- 34 years. 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 as seminoma and nonseminoma. Testicular cancer has high cure rates even in disseminated stage of disease. The chemotherapy mostly contributed to these results, but surgery is an unavoidable part of this success. In significant number of these patients treatment algorithms today have intention to offer the same cure rates with minimally aggressive therapy. The following text presents the clinical guidelines in order to standardize procedures and criteria for diagnosis, treatment, and follow-up of patients with testicular cancer in the Republic of Croatia

Clinical Recommendation for Diagnostics, Treatment and Monitoring of Patients with Prostate Cancer

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.Prostate adenocarcinoma is the most common solid neoplasm in male population in Croatia. It is often asymptomatic. The finding of PSA rise is the most common reason for diagnostic workout. Treatment plan is based on TNM classification, grade group 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 metastatic disease appropriate treatment is chemotherapy or secondary hormonal therapy. The following paper presents the clinical guidelines to standardize procedures for the diagnosis, treatment and follow-up of patients with prostate cancer in the Republic of Croatia

CLINICAL RECOMMENDATIONS FOR TREATING AND MONITORING PATIENTS WITH RENAL CANCER

Svjetlostanični tip karcinoma bubrežnih stanica najčešći je oblik raka bubrega. Klinički je uglavnom asimptomatski, a samo se kod manjeg postotka bolesnika očituje hematurijom, tupom boli i palpabilnom masom u trbuhu. Najčešće se otkrije slučajno tijekom radioloških pregleda. Dijagnoza raka bubrega potvrđuje se patohistološkim nalazom nakon provedene dijagnostičke obrade. Odluka o liječenju donosi se temeljem kliničke procjene stadija bolesti i drugih čimbenika rizika. Ovisno o tome, mogućnosti liječenja uključuju kirurški zahvat te s obzirom na visoku rezistenciju raka bubrega na kemoterapiju i hormonsku terapiju, primjenu ciljane terapije (imunoterapija, inhibicija aktivnosti receptora tirozin kinaze) te palijativnu radioterapiju. U tekstu koji slijedi predstavljene su kliničke upute s ciljem standardizacije postupaka i kriterija postavljanja dijagnoze, upravljanja i liječenja te praćenja bolesnika s rakom bubrega u Republici Hrvatskoj.Clear cell renal carcinoma is the most common kidney cancer. It is generally asymptomatic. A small percentage of patients present with hematuria, flank pain and abdominal mass. It is usually detected accidentally during radiologic examination. The diagnosis of kidney cancer is confirmed by pathohistological findings after completion of the diagnostic process. The decision about treatment is made based on clinical assessment of disease stage and other risk factors. Depending on that, treatment options include surgery, and considering high resistance of kidney cancer on chemotherapy and hormone therapy, use of targeted therapies (immunotherapy, tyrosine kinase inhibitors) and palliative radiotherapy. The following text presents the clinical guidelines in order to standardize procedures and criteria for the diagnosis, management, treatment and monitoring of patients with kidney cancer in the Republic of Croatia

Kliničke upute za dijagnostiku, liječenje i praćenje bolesnika oboljelih od raka mokraćnog mjehura Hrvatskoga onkološkog društva i Hrvatskoga urološkog društva Hrvatskoga liječničkog zbora [Clinical guidelines for diagnosing, treatment and monitoring patients with bladder cancer - Croatian Oncology Society and Croatian Urology Society, Croatian Medical Association]

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