Clinical Oncology

[Management of renal cancer]

MARÁZ Anikó, SZŰCS Miklós

FEBRUARY 20, 2014

Clinical Oncology - 2014;1(01)

[Targeted anti-cancer agents are used as standard therapies in case of advanced or metastatic clear cell renal carcinoma. Neovascularisation plays an important role in the progression of hypervascularized cancers. Vascular endothelial growth factor (VEGF) is the key molecule in this mechanism. Most of the registered agents inhibit the angiogenesis by blocking the VEGF signalling pathway. It can occur if an antibody binds to the VEGF, so the linkage to the receptor is blocked. This happens in case of bevacizumab. Another mechanism is the inhibition of the intracellular compound of VEGF receptor by tyrosine kinase inhibitors (TKI). Sorafenib, sunitinib, pazopanib and axitinib belong to this group. Other well-known mechanism of action is the inhibition of mammalian target of rapamycin (mTOR) receptor, like temsirolimus and everolimus. Based on randomised controlled trials sunitinib, pazopanib or IFNα-bevacizumab combination is recommended fi rst-line according to the international recommendations in case of good and moderate prognosis. For patients with poor prognosis temsirolimus is the standard therapy. In second-line, after ineffective cytokine therapy, sorafenib, pazopanib and axitinib are the supported options. If TKI is ineffective, everolimus or axitinib can be administered. In the latest recommendations sorafenib is another possible option (off label). After two TKIs, only everolimus is registered for third-line therapy. Life expectancy of patients can further be improved as the number of targeted drugs increases, more effective agents appear and as appropriate sequences and their benefi cial effects are recognised.]



Further articles in this publication

Clinical Oncology

[First-line treatment of epithelial ovarian cancer]


[The restructuration of Hungarian oncological attendance and medicinal fi nancing resulted in the more intensive participation of clinical oncologists in the therapy of patients with ovarian cancer. The aim of the authors was not to defi ne the taxative therapeutic recommendations, but to give an overview on the development of the therapy and to introduce the deliberation aspects and therapeutic alternatives. While the primary and secondary prevention have developed in case of cervical cancer - with the possibility of eradication - the improvement of surgical techniques and clinical oncological treatments may result in the decrease of mortality in ovarian cancer. It is important to emphasis that only the appropriately aligned application of the two therapeutic modalities can lead to the desired outcome. It has become clear by the end of the ‘90s, that paclitaxel-carboplatin combination is the standard chemotherapy against ovarian cancer. Alternative cytostatic treatments like intraperitoneal treatment and triplets were not breakthroughs. The dose intensive treatment increased the survival rates besides good tolerability, however the results require further confi rmation. Neoadjuvant therapy should be considered in case of patients with advanced and metastatic disease in selected cases. Recently, therapeutic use of angiogenesis inhibition comes with signifi cant improvement. Bevacizumab is the fi rst of targeted therapies, and studies on the effectiveness of similar compounds are under way.]

Clinical Oncology

[How long the colorectal cancer should be treated?]


[Colorectal cancer is one of the leading cancer-related death worldwide. The optimal treatment duration of metastatic colorectal cancer depends on the individual treatment aim and it should be decided by an onco-team and by the patient. In this review several actual issues will be discussed, like the optimal duration of therapy to reach the secondary resection, the accepted response rate and best treatment strategy in case of non-operable colorectal cancer. Furthermore, emphasis is given to the most useful endpoints to evaluate different therapeutic approaches.]

Clinical Oncology

[Management of febrile neutropenia in the oncological practice]


[Febrile neutropenia is one of the most feared complications of anti-tumor therapy. It can either herald potentially fatal infection or contribute to suboptimal dose-intensity of cancer treatment. Optimal management of affected patients is based upon a multi-disciplinary approach dependent on several factors. Knowledge on institutional epidemiology and predefi ned management strategies improve quality and outcome of anti-infective therapy. In an era of more and more resistant pathogens and erosion of the antimicrobial armamentarium clinicians taking care of cancer patients carry increased responsibility in their professional activity. Here questions of practical importance related to prevention and therapy of neutropenic infections are outlined.]

Clinical Oncology

[Management of pancreatic cancer today]


[Pancreatic cancer (PC) is a major health problem with a poor prognosis. The number of patients with PC is increasing globally. There are no screening tests for early detection of PC, but even when diagnosed early, surgery is possible in only a minority of cases. Managing PC remains a big challenge. For selected patients with borderline or unresectable disease, neoadjuvant therapy offers the potential for tumor downstaging. In patients with resectable disease, adjuvant chemotherapy improves the fi ve year survival rate, whereas the use of adjuvant radiochemotherapy is still controversial. In metastatic cancer, monotherapy with gemcitabine remained the main therapeutic option during more than 10 years. Many different combinations with other drugs and new targeted therapies have been tested with gemcitabine. Only a combination of erlotinib and gemcitabine has shown a modest survival benefi t until now. Many gene alterations that directly contribute to pancreas tumorigenesis have been identifi ed or are under active investigation. Recently, the FOLFIRINOX regimen has been reported to be more active than gemcitabine in selected metastatic patients. Quality of life is an extremly important factor, when treating a patient with PC. CA 19-9 serum level can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. There is a strong need for other predictive biomarkers to select patients, who might benefi t from available and new therapeutic options.]

Clinical Oncology

[Resistancy and/or progression - Failure or only a short stop]


[Nowadays, with the continuously in creasing demand for targeted diagnostics and therapy, we are approaching an ideal stage when the most effective treat ment for a given patient could be selected. However, some basic problems are still waiting to be solved. One major hurdle is the heterogeneity, the formation of subclones with different signifi cance during progression, but with the capacity to overgrow after the failure of the initial therapy. The importance of this phenomenon is refl ected in the daily practice where targeted therapy is allowed to treat only locally extended or metastatizing tumors. Therefore, it is not as to nishing, that the clinical success is usually tem po rary, the disease in spite of the good response at the beginning will progress. The main reason is the resistancy against the carefully analysed and applied therapeutic drugs, which has several options (e.g. new mutations, crosstalks between pathways, faults of feed-backs, etc.). This review focuses on the acquired resistancy with some relevant examples. Among the open questions we can recall e.g. the resistancy in combination therapy, or the suggested link between resistancy and progression including the potential use of drug rechallenge.]

All articles in the issue

Related contents

Clinical Oncology

[Non-surgical treatment of the biliary tract and gallbladder cancer]

PIKÓ Béla, LACZÓ Ibolya

[Biliary tract cancers are rare, hence only a few high level of evidences related to their treatment are available. The successful treatment and the only chance for long-term survival are based on the radical surgical resection. After the fl uoropyrimidin based protocols chemotherapy regimens prefer gemcitabine combinations (cisplatin, oxaliplatin, capecitabine) or FOLFIRINOX, considering the patient performance status as well. There are no registered targeted therapy in this indication, the most experiences were acquired with erlotinib; nowadays the optimal treatment can be selected by the molecular genetic profi le of the tumour and not by the results of the clinical studies. The radiotherapy and the radiochemotherapy can be administered preoperatively, postoperatively and for palliation as well, in addition to the conventional percutaneous radiotherapy, brachytherapy, intensity-modulated radiotherapy, intraoperative irradiation, radioembolization can also be administered depending on the technical equipments. Besides the photodynamic therapy and several ablation therapies, even interventional radiological procedures can play a signifi cant role.]

Clinical Oncology

[Signaling pathways in cancer stem cells (Notch, Hedgehog, Wnt)]


[OThe key regulators in the embryonic life, and later in the differentiation of tissues and organs are the evolutionary reserved signalling pathways, as Notch, Hedgehog and Wnt. Mutations of these pathways have been identifi ed in many tumor types, increasing the risk to the appearance of cancer stem cells (CSC), with very similar geno- and phenotype as normal stem cells have. Such CSCs with stemness functions can be developed not only from normal stem cells, but also from progenitor and differentiated cells. The main characteristics of CSC are the self maintenance, slow growth rate, very effective DNA-repair system, etc. All of these can contribute to the resistance. Further problems are the low number of CSC in the whole tumor mass, which makes rather diffi cult to achieve the effective drug concentration in CSC. The mentioned ancient pathways interact with many other pathways to form a network, which can infl uence the strategy of therapy. No doubt, that these pathways are promising targets, however, till now the clinical effectiveness is very low due to some reasons mentioned above. Nevertheless, some drugs are already in clinical use, either as monotherapy or part of the combinations. Little is known about the relationship between the pathways and the microenvironment, which has an outstanding role in the cellular activities, sometimes resulting opposite output. It is a great challenge to design effective drugs against CSC, similarly to fi nd reliable predictive biomarkers, which unfortunately still missing, since a reasonable drug-marker interactions would speed up the personalized treatment.]

Clinical Oncology

[The role of EGFR receptor family in the oncological practice]


[The EGFR receptor family is a set of membrane tirosine kinase receptors with signifi cant homology which are responsible for cellular activation through intracellular signaling due to ligand binding. The four members of the family (EGFR1, EGFR2/HER2/neu, EGFR3/HER3, EGFR4/HER4) earned special interest in tumor biology while becoming one of the most potent targets of anti-cancer therapies. Changes in the receptor expression or in the kinase activity fundamentally modify cellular functions, survival and tumorigenic potential. Moreover, mutations are associated with reduced or altered treatment effi cacy. The basic function and major genetic and biological mechanisms affecting the function of EGFR receptors and related therapies are subjects of this overview.]

Clinical Oncology

[Radiological response evaluation of targeted therapy]


[The objective assessment of the changes in the tumor burden along with cancer therapy has essential importance. Recently, the quantitative evaluation of the radiological tumor response was undergone several changes. For conventional chemotherapy of solid tumors the standard procedure has been RECIST since 2000. The targeted therapies trigger other pathophysiological changes in the cells than the cytotoxic agents, accordingly the morphological changes show a new picture. Therefore the targeted therapies require a new evaluation system, that takes into consideration not only the tumor size, but other changes as well, the changes of attenuation that corresponds with the proportion of the viable cells. In case of the targeted therapies in substantial clinical was experienced even without signifi cant morphological changes in the tumour size. As a consequence, the traditional, size-based criteria system can underestimate the effi ciency of the new types of treatments. To eliminate this problem new evaluation systems were created taking the tumortypes and treatment protocolls into consideration. The estimation of the early tumor response to targeted therapy also has high importance. In assessment of the response functional imaging methods are used more frequently. The role of PET has already been defi ned in numerous tumortypes, however the determination of the position of some promising functional examinations still require further studies.]

Lege Artis Medicinae

[New possibilities in the management of hepatocellular carcinoma]

DANK Magdolna

[The prognosis of primary hepatocellular carcinoma (HCC) has been poor until recently. Most patients are diagnosed at an advanced stage, with a poor liver function, thus therapeutic possibilities are limited. In high-risk patients, active surveillance and HCC screening is essential for early diagnosis. Experience with systemic chemotherapy has been disappointing with low response rates and high rates of adverse effects. Recently, novel treatment options have emerged, including the use of specific targeted agents, blockers of signaling pathways involved in hepatocarcinogenesis. Sorafenib, an oral multikinase- inhibitor is the first systemic agent to demonstrate survival benefit in advanced hepatocellular cancer. Several new, promising therapeutic options are being tested in clinical trials. The present review gives an overview of evolving diagnostic and therapeutic strategies.]