Clinical trials in oncology

Klinične raziskave ali klinična preskušanja so raziskave, ki vključujejo ljudi. Na njihovih izsledkih temelji vsakodnevna obravnava bolnikov, zdravljenje, ki temelji na dokazih. Klinična preskušanja razvrščamo v več faz. V fazi I ugotavljamo predvsem toksičnost, v fazi II aktivnost zdravila pri določeni bolezni in v fazi III primerjamo učinkovitost nove oblike zdravljenja s trenutno priporočenim zdravljenjem določene bolezni. V želji po hitrejši informaciji o učinkovitosti številnih novih, predvsem tarčnih zdravil, se je razvil novi tip kliničnih raziskav, klinične raziskave tipa %košara%, %dežnik% in %prilagoditev%. Vse klinične raziskave morajo izpolnjevati stroga merila, ki zagotavljajo, da so bolniki v raziskavah zaščiteni in so rezultati pravilno ovrednoteni. Dostopnost do raziskav je pomembna za razvoj stroke, pa tudi za bolnike, saj v okviru teh lahko dobijo dodatne možnosti zdravljenja. Zato je pomembno, da zdravniki bolnike spodbujamo k sodelovanju v kliničnih raziskavah.Clinical trials or clinical studies refer to research that is done in people. Their results are the backbone of daily clinical practice, namely evidence-based medicine. Clinical trials involve several phases. The main purpose of a phase I trial is to determine the safety of treatment, a phase II trial aims to determine if the new treatment is effective in treating a certain cancer, and a phase III trial compares the new treatment to the current standard treatment for a certain type of cancer. Aimed at providing prompt information on the effectiveness of many new agents, especially targeted drugs, new types of clinical study designs have been developed, namely basket trials, umbrella trials, and adaptive trials. All clinical trials have to meet strict criteria to ensure that patient rights are protected and that the results are properly evaluated. Accessibility to clinical trials is important for the development of oncology and for patients as well, as clinical trials may provide them with additional treatment. It is, therefore, important that doctors encourage patients to participate in clinical trials

Novosti v dopolnilnem zdravljenju HER2-pozitivnega raka dojke

Although trastuzumab-based regimens have improved both systemic control and overall survival in the patients with HER2-positive breast cancer, in some of these patients, tumor progression occurs despite trastuzumab treatment. New target therapies are searched for these patients. The most promising and, in terms of clinical use, the most developed is lapatinib, a small molecule, tyrosine-kinase inhibitor that targets not only HER2- but also HER1-receptor. It is already used for treating the HER2-positive metastatic breast cancer patients after failure of trastuzumab therapy, but its effectiveness in adjuvant therapy has not been proven yet. ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization) is a randomized phase-three multi-center study of adjuvant lapatinib, trastuzumab, their sequence and their combination in the patients with HER2 positive primary breast cancer.Ni abstrakta

Spynal Cord Compession

Kompresija hrbtenjače je zaplet rakave bolezni, ki redko ogroža bolnikovo življenje, če pa je ne odkrijemo, lahko že v nekaj urah vodi do nepopravljive okvare hrbtenjače s trajno paralizo. Do kompresije hrbtenjače največkrat pride pri bolnikih z zasevki v hrbtenici, redkeje je posledica neposrednega vraščanja mehkotkivne tumorske mase v hrbtenični kanal. Do tega zapleta najpogosteje pride pri bolnikih z rakom pljuč, dojke, prostate, ščitnice, ledvice in s plazmocitomom. Bolnik kot prve težave navaja bolečine v hrbtenici, temu se pridružijo nevrološki izpadi. Nivo kompresije hrbtenjače določimo z nevrološkim pregledom. Od diagnostičnih metod je na prvem mestu rentgensko slikanje, ki pa nam pokaže le skeletne nepravilnosti, zato je za opredelitev kompresije hrbtenjače nujna MRI. Pri grozeči kompresiji hrbtenjače moramo ukrepati takoj. Bolniku svetujemo mirovanje, predpišemo mu analgetike in glukokortikoide. Izbira zdravljenja je odvisna od narave bolezni, obsega prizadetosti hrbteničnega kanala in bolnikovega splošnega stanja. Obsega kirurško zdravljenje v kombinaciji z obsevanjem in sistemskim zdravljenjem ali pa le obsevanje skupaj s sistemskim zdravljenjem ali brez njega. V vsakem primeru je pri sumu, da gre za kompresijo hrbtenjače, pomembno, da zdravljenje začnemo čim prej.Spinal cord compression is a complication of cancer that is usually not immediately life-threatening, but can lead to significant morbidity in a different way. The mechanisms by which tumors can compress the spinal cord are hematogenous spread of tumor cells to the vertebra, or rarely, by direct extension of paraspinal tumors into the spine. Such compression is predominantly due to metastatic spread of the lung, breast, prostate, thyroid, kidney cancer or multiple myeloma. The most common presentation of spinal cord compression is back pain that is followed by neurological impairment. The level of compression should be determined by physical examination. A standard x-ray is generally ordered first, but it shows only bony lesions. However, MRI is the imaging technique of choice for suspected spinal cord compression. Spinal cord compression needs urgent treatment. Patient has to be prescribed analgetics and glucocorticoids and rest is advised. The choice of treatment depends on primary cancer type, degree of spinal cord damage and general performance status of the patient. Surgery in combination with radiotherapy and systemic therapy is treatment of choice in some cases, but radiotherapy alone or in combination with systemic therapy is sometimes an option. In any case, it is important to start the treatment as soon as possible

Kompresija hrbtenjače

Spinal cord compression is a complication of cancer that is usually not immediately life-threatening, but can lead to significant morbidity in a different way. The mechanisms by which tumors can compress the spinal cord are hematogenous spread of tumor cells to the vertebra, or rarely, by direct extension of paraspinal tumors into the spine. Such compression is predominantly due to metastatic spread of the lung, breast, prostate, thyroid, kidney cancer or multiple myeloma. The most common presentation of spinal cord compression is back pain that is followed by neurological impairment. The level of compression should be determined by physical examination. A standard x-ray is generally ordered first, but it shows only bony lesions. However, MRI is the imaging technique of choice for suspected spinal cord compression. Spinal cord compression needs urgent treatment. Patient has to be prescribed analgetics and glucocorticoids and rest is advised. The choice of treatment depends on primary cancer type, degree of spinal cord damage and general performance status of the patient. Surgery in combination with radiotherapy and systemic therapy is treatment of choice in some cases, but radiotherapy alone or in combination with systemic therapy is sometimes an option. In any case, it is important to start the treatment as soon as possible.Kompresija hrbtenjače je zaplet rakave bolezni, ki redko ogroža bolnikovo življenje, če pa je ne odkrijemo, lahko že v nekaj urah vodi do nepopravljive okvare hrbtenjače s trajno paralizo. Do kompresije hrbtenjače največkrat pride pri bolnikih z zasevki v hrbtenici, redkeje je posledica neposrednega vraščanja mehkotkivne tumorske mase v hrbtenični kanal. Do tega zapleta najpogosteje pride pri bolnikih z rakom pljuč, dojke, prostate, ščitnice, ledvice in s plazmocitomom. Bolnik kot prve težave navaja bolečine v hrbtenici, temu se pridružijo nevrološki izpadi. Nivo kompresije hrbtenjače določimo z nevrološkim pregledom. Od diagnostičnih metod je na prvem mestu rentgensko slikanje, ki pa nam pokaže le skeletne nepravilnosti, zato je za opredelitev kompresije hrbtenjače nujna MRI. Pri grozeči kompresiji hrbtenjače moramo ukrepati takoj. Bolniku svetujemo mirovanje, predpišemo mu analgetike in glukokortikoide. Izbira zdravljenja je odvisna od narave bolezni, obsega prizadetosti hrbteničnega kanala in bolnikovega splošnega stanja. Obsega kirurško zdravljenje v kombinaciji z obsevanjem in sistemskim zdravljenjem ali pa le obsevanje skupaj s sistemskim zdravljenjem ali brez njega. V vsakem primeru je pri sumu, da gre za kompresijo hrbtenjače, pomembno, da zdravljenje začnemo čim prej

Klinične raziskave v onkologiji

Clinical trials or clinical studies refer to research that is done in people. Their results are the backbone of daily clinical practice, namely evidence- based medicine. Clinical trials involve several phases. The main purpose of a phase I trial is to determine the safety of treatment, a phase II trial aims to determine if the new treatment is effective in treating a certain cancer, and a phase III trial compares the new treatment to the current standard treatment for a certain type of cancer. Aimed at providing prompt information on the effectiveness of many new agents, especially targeted drugs, new types of clinical study designs have been developed, namely basket trials, umbrella trials, and adaptive trials. All clinical trials have to meet strict criteria to ensure that patient rights are protected and that the results are properly evaluated. Accessibility to clinical trials is important for the development of oncology and for patients as well, as clinical trials may provide them with additional treatment. It is, therefore, important that doctors encourage patients to participate in clinical trials.Klinične raziskave ali klinična preskušanja so raziskave, ki vključujejo ljudi. Na njihovih izsledkih temelji vsakodnevna obravnava bolnikov, zdravljenje, ki temelji na dokazih. Klinična preskušanja razvrščamo v več faz. V fazi I ugotavljamo predvsem toksičnost, v fazi II aktivnost zdravila pri določeni bolezni in v fazi III primerjamo učinkovitost nove oblike zdravljenja s trenutno priporočenim zdravljenjem določene bolezni. V želji po hitrejši informaciji o učinkovitosti številnih novih, predvsem tarčnih zdravil, se je razvil novi tip kliničnih raziskav, klinične raziskave tipa %košara%, %dežnik% in %prilagoditev%. Vse klinične raziskave morajo izpolnjevati stroga merila, ki zagotavljajo, da so bolniki v raziskavah zaščiteni in so rezultati pravilno ovrednoteni. Dostopnost do raziskav je pomembna za razvoj stroke, pa tudi za bolnike, saj v okviru teh lahko dobijo dodatne možnosti zdravljenja. Zato je pomembno, da zdravniki bolnike spodbujamo k sodelovanju v kliničnih raziskavah

Update on Adjuvant Treatment of HER2-Positive Breast Cancer

Although trastuzumab-based regimens have improved both systemic control and overall survival in the patients with HER2-positive breast cancer, in some of these patients, tumor progression occurs despite trastuzumab treatment. New target therapies are searched for these patients. The most promising and, in terms of clinical use, the most developed is lapatinib, a small molecule, tyrosine-kinase inhibitor that targets not only HER2- but also HER1-receptor. It is already used for treating the HER2-positive metastatic breast cancer patients after failure of trastuzumab therapy, but its effectiveness in adjuvant therapy has not been proven yet. ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization) is a randomized phase-three multi-center study of adjuvant lapatinib, trastuzumab, their sequence and their combination in the patients with HER2 positive primary breast cancer

A Prospective Cohort Study on Cardiotoxicity of Adjuvant Trastuzumab Therapy in Breast Cancer Patients

Abstract Background: Cardiotoxicity is an important side effect of trastuzumab therapy and cardiac surveillance is recommended

Hypercalcemia in Cancer Patients

Hiperkalcemija je najpogostejša presnovna motnja, ki ogroža bolnika z rakom. Najpogostejša je pri solidnih rakih (rak pljuč, dojke), pogosta pa je tudi pri hematoloških malignomih (zlasti pri multiplem mielomu). Glavni vzrok hiperkalcemije zaradi rakave bolezni je povečana resorpcija kosti in nezadostno izločanje kalcija prek ledvic. Najpogostejši sta osteolitična in humoralna hiperkalcemija. Osteolitična je posledica večje kostne resorpcije, njeni mediatorji pa so različni citokini na mestu zasevka. Humoralna hiperkalcemija je posledica izločanja paratiroidnemu hormonu podobnega peptida (PTH-rP). Prvi znaki hiperkalcemije so žeja, poliurija, slabost, splošna utrujenost in zaprtje. Pri vrednosti serumskega kalcija nad 3,0 mmol/l se začnejo pojavljati znaki prizadetosti osrednjega živčevja, poveča se nevarnost za srčne aritmije, pri dalj časa trajajoči hiperkalcemiji lahko pride do okvare ledvic. Uspešno zdravljenje temelji na intenzivni hidraciji s fiziološko raztopino, vzpodbujanju izločanja kalcija z diuretiki po doseženi normovolemiji in zaviranju kostne resorpcije z bisfosfonati (zolendronatom, pamiodronatom ali ibandronatom). Vendar pa bomo hiperkalcemijo dolgotrajno uspešno obvladovali le, če bomo sočasno zdravili rakavo bolezen, ki je privedla do nje. Če zdravljenje maligne bolezni ni bilo uspešno, tudi zdravljenje hiperkalcemije ni smiselno.Hypercalcemia is the most common life-threatening metabolic disorder in cancer patients. Solid tumors (such as lung or breast cancer) as well as certain hematologic malignancies (particularly multiple myeloma) are most frequently associated with hypercalcemia. The fundamental cause of cancer–induced hypercalcemia is increased bone resorbtion and inadequate renal clearance. The most common types of hypercalcemia are osteolytic and humoral. The osteolytic hypercalcemia results in increased local osteoclastic bone resorbtion mediated by different cytokines. Humoral hypercalcemia is caused by secretion of parathyroid hormone-related protein (PTH-rP). Early symptoms of hypercalcemia are thirst, polyuria, nausea, vomiting, fatigue and constipation. Signs and symptoms of central nerve system impairment and a higher risk of cardiac arrhythmias appear when serum calcium level rises beyond 3,0 mmol/l. Renal function deterioration could evolve in long-lasting hypercalcemia. The cornerstones of successful antihypercalcemic therapy are rehydration with normal saline, calciuresis with the use of loop diuretics after normovolemia has been restored and inhibition of bone resorbtion with the use of intravenous bisphosphonates (zolendronate, pamiodronate or ibandronate). However, long-term efficacy of cancer-induced hypercalcemia will be successful only if it is accompanied with the effective treatment of underlying malignant disease. When all available cancer therapies have failed, also treatment of hypercalcemia is of no sense

The role of immune checkpoint inhibitors in the treatment of cancer of unknown origin

Rak neznanega izvora (RNI) je histološko potrjen rak, pri keterem anatomski izvor kljub izčrpni diagnostiki ostane nerazpoznan. Trenutno nimamo dokazov, da bi identifikacija tkivnega izvora RNI in usmerjeno zdravljenje izboljšalo preživetje bolnikov, v primerjavi z empiričnim zdravljenjem, je pa pomembno, da v skupini bolnikov z RNI identificiramo in ustrezno zdravimo tiste bolnike, ki jih uvrščano v prognostično ugodno skupino. Zaviralci imunskih kontrolnih točk (ZIKT) so učinkovita zdravila za zdravljenje malignih bolezni različnega izvora. V literaturi najdemo anekdotične opise učinkovitosti te skupine zdravil tudi pri bolnikih z rakom neznanega izvora (RNI). Rezultati edine do sedaj zaključene raziskave, ki je usmerjeno proučevala ZIKT pri bolnikih z RNI, NivoCUP, faza 2, kažejo na potencialno učinkovitost nivolumaba pri bolnikih z RNI. Objektivni odgovor je bil dosežen pri 21,4% bolnikov, med njimi tudi tistih z verjetno kemo-rezistentnimi tumorji, pri nekaterih bolnikih so bili odgovori na zdravljenje dolgotrajni. Rezultati sicer potrebujejo potrditev z obsežnejšo, randomizirano raziskavo. Pembrolizumab je trenutno edini ZIKT, ki ima s strani ameriške regulatorne organizacije (FDA) odobritev za agnostično zdravljenje v primeru dokazane okvare proteinov za popravljanje neujemanja oz. visoke mikrosatelitne nestabilnosti (MSI-H/MMRd) ali visokem tumorskem bremenu v DNK tumorske celice (TMB-H). Potrebujemo še dodatne prediktivne bio-markerje, s pomočjo katerih se bomo bolj zanseljivo odločali o optimalnem zdravljenju bolnikov z RNI

Hiperkalcemija pri bolniku z rakom

Hypercalcemia is the most common life-threatening metabolic disorder in cancer patients. Solid tumors (such as lung or breast cancer) as well as certain hematologic malignancies (particularly multiple myeloma) are most frequently associated with hypercalcemia. The fundamental cause of cancer–induced hypercalcemia is increased bone resorbtion and inadequate renal clearance. The most common types of hypercalcemia are osteolytic and humoral. The osteolytic hypercalcemia results in increased local osteoclastic bone resorbtion mediated by different cytokines. Humoral hypercalcemia is caused by secretion of parathyroid hormone-related protein (PTH-rP). Early symptoms of hypercalcemia are thirst, polyuria, nausea, vomiting, fatigue and constipation. Signs and symptoms of central nerve system impairment and a higher risk of cardiac arrhythmias appear when serum calcium level rises beyond 3,0 mmol/l. Renal function deterioration could evolve in long-lasting hypercalcemia. The cornerstones of successful antihypercalcemic therapy are rehydration with normal saline, calciuresis with the use of loop diuretics after normovolemia has been restored and inhibition of bone resorbtion with the use of intravenous bisphosphonates (zolendronate, pamiodronate or ibandronate). However, long-term efficacy of cancer-induced hypercalcemia will be successful only if it is accompanied with the effective treatment of underlying malignant disease. When all available cancer therapies have failed, also treatment of hypercalcemia is of no sense.Hiperkalcemija je najpogostejša presnovna motnja, ki ogroža bolnika z rakom. Najpogostejša je pri solidnih rakih (rak pljuč, dojke), pogosta pa je tudi pri hematoloških malignomih (zlasti pri multiplem mielomu). Glavni vzrok hiperkalcemije zaradi rakave bolezni je povečana resorpcija kosti in nezadostno izločanje kalcija prek ledvic. Najpogostejši sta osteolitična in humoralna hiperkalcemija. Osteolitična je posledica večje kostne resorpcije, njeni mediatorji pa so različni citokini na mestu zasevka. Humoralna hiperkalcemija je posledica izločanja paratiroidnemu hormonu podobnega peptida (PTH-rP). Prvi znaki hiperkalcemije so žeja, poliurija, slabost, splošna utrujenost in zaprtje. Pri vrednosti serumskega kalcija nad 3,0 mmol/l se začnejo pojavljati znaki prizadetosti osrednjega živčevja, poveča se nevarnost za srčne aritmije, pri dalj časa trajajoči hiperkalcemiji lahko pride do okvare ledvic. Uspešno zdravljenje temelji na intenzivni hidraciji s fiziološko raztopino, vzpodbujanju izločanja kalcija z diuretiki po doseženi normovolemiji in zaviranju kostne resorpcije z bisfosfonati (zolendronatom, pamiodronatom ali ibandronatom). Vendar pa bomo hiperkalcemijo dolgotrajno uspešno obvladovali le, če bomo sočasno zdravili rakavo bolezen, ki je privedla do nje. Če zdravljenje maligne bolezni ni bilo uspešno, tudi zdravljenje hiperkalcemije ni smiselno