Clinical Oncology

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


FEBRUARY 20, 2014

Clinical Oncology - 2014;1(01)

[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.]



Further articles in this publication

Clinical Oncology

[Management of renal cancer]

MARÁZ Anikó, SZŰCS Miklós

[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.]

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

[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

[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.]

All articles in the issue

Related contents

Lege Artis Medicinae

[Palliative chemotherapy of solid tumors]


[Palliative chemotherapy, as defined, a cytotoxic treatment where the expected result is not sufficient enough to cure the patient but it could relieve the cancer related symptoms. In other words, it is such a treatment where the chance of symptomatic improvement means an overall advantage to the patient compared to the possible disadvantages of toxicity. In the 70s and 80s, only the objective response rate, relapse free interval, and overall survival rates were selected as endpoints when the activity of anticancer agents were investigated. In these studies it was observed that a considerable amount of patient showed significant symptomatic improvement even though the treatment was ineffective according to the measured endpoints. Today, the measurement of quality of life is one of the standard endpoint of such studies. Moreover, quality of life is considered as the most important independent factor when palliative chemotherapy is initiated. It should be noted that remission is not the only and final benefit of chemotherapy. The role and options of palliative chemotherapy in certain tumors are discussed.]

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[Frequency and risk factors of “de novo” tumors after kidney transplantation ]


[After kidney transplantation, the administration of immunosuppressive therapy not only renders the patient susceptible to infections, but it may also damage the function of tumor cell recognition and elimination. Our study was performed at the Department of Surgery, University of Szeged. After establishing the inclusion criteria, 570 patients were involved in the study. We examined the age, sex, immunosuppressive therapy of the patients, and searched for the rela­tionship between the different immunosuppressive agents and the type of the tumor. In 81 cases, de novo cancer was diagnosed. Among patients treated with cyclosporin and tacrolimus there was no significant difference in the mean age (p = 0.734) and body mass index (p = 0.543). There was no significant difference in graft function between the two groups of patients (Tac vs Cyc; 44 vs 20). Related to the time passed since the trans­plantation to diagnosing the tumors the earliest were prostate and cervix cancers however without significant difference. Skin cancers are the most frequent followed by post-transplant lym­pho­prolife­ra­tive diseases. The increasing risk of developing tumors is mainly due to immunosuppressive therapy. ]

Lege Artis Medicinae



[Digital cross-sectional imaging techniques, especially computed tomography (CT) and magnetic resonance imaging (MRI) play an important role in the diagnosis of pathologic conditions affecting the head and neck. MRI, because of its superb soft tissue contrast resolution and multiplanar imaging ability gives the most information regarding the origin and the extent of a laesion, intracranial extension, perineural-, as well as bone marrow involvement and play key role in the management of different diseases. Careful observation of the characteristic radiological features usually leads to correct diagnosis, however, some of the lesions are not typical, looking very similar and can be difficult to differentiate from each other. The purpose of the present article is to provide an overview of the most common pathologic conditions examined with MRI.]

Clinical Oncology

[EMT (Epithelial-Mesenchymal transition) – CSC (Cancer Stem Cells)]


[The effi cacy of the antitumor therapy is usually limited due to the resistance against the chemotherapy. One of the most important reason of the secunder resistance is the intratumoral heterogeneity, which is the consequence of the variety tumor phenotypes in the same tumor. Such clonal heterogeneity develops during the tumor growth or tumor therapy. The cancer stem cells (CSC), according to the concept, can determine the progression of the tumor, including metastatization, which probably the major enemy for clinical oncology. This activity of CSC, in tumors with epithelial origin, is supported by a change from epithelial to mesenchymal phenotype (epithelial-mesenchymal transition); but not entirely. The CSC phenotype is very similar to characteristic of the normal stem cells, as resistance, self-renewal etc. The mechanisms of these concepts is known only partially, but the technical advances contribute to the identifi cation of key genetic and epigenetic regulatory pathways. If such improvement becomes real, we can be much ahead both with markers and therapeutic targets.]

Clinical Neuroscience

[Surgery of ventral intradural midline cervical spinal pathologies via anterior cervical approach: our experience]


[Introduction - The surgical removal of the cervical intradural pathologies located ventrally carries a high risk. According to the anatomical situation and the increasing experience with anterior cervical approach and corpectomy revealed the reality to remove the ventral midline pathologies this way. The anterior approach which require corpectomy preferable to cervical intradural lesions located ventrally at the midline. In the literature have described anterior approach for intradural cervical lesions in very limited cases. Case - The authors present five cases of intradural ventral cervical spinal pathologies, where removal was done via anterior cervical approach with corpectomy. Two of the cases were intradural meningeomas, one intramedullary cavernoma, one ventral arachnoid cyst and one malignant neurogenic tumour. The approach was described elsewhere. The corpectomy gave a relatively wide window to explore the pathologies and under operative microscope the local control of removal was fairly well. After the total removal of tumours and cavernoma, and fenestration of arachnoid cyst to the subarachnoid space watertight dural closure was made and the cervical spine was stabilized with autolog iliac bone graft, plate and screws. The recovery of the patients was well and there were no postoperative complications. Conclusions - The anterior cervical approach with corpectomy seems to be a real and safe way to explore and remove the cervical ventral midline pathologies. Postoperative MRI has a great value in early control after the surgery and for follow up the patients.]