Clinical Oncology

[Radiochemotherapy - questions/answers]

PIKÓ Béla, LACZÓ Ibolya

FEBRUARY 10, 2017

Clinical Oncology - 2017;4(01)

[During chemoradiotherapy the two main non-surgical anticancer methods are combined to improve the treatment outcomes. The theoretical possibilities of interactions and the most frequently used drugs will be presented here, emphasizing that although both the radiation therapy and the drugs need to be administered in full dose in practice considering the summarization of side effects we often have to make compromises. The treatments of the most frequent indications (brain, head and neck, oesophagus, lung, stomach, pancreas, rectum, bladder, cervix, soft tissue sarcoma) will be demonstrated. Since there are several drugs and drug combinations that are not included in the Hungarian registered anticancer therapies, for their off-label use the permission of the National Institute of Pharmacy and Nutrition is required. To choose the optimal treatment (during planning the optimal place of chemoradiotherapy, agents and doses) the opinion of a multidisciplinary team is necessary]



Further articles in this publication

Clinical Oncology

[Cell cycle as therapeutic target – CDK4/6 inhibition]


[One of the most important decision of a cell: to live or die. If survival is the choice, there are three options: proliferate, to stay in sleeping state for a while, or differentiate in order to perform its specifi c function. These decisions are under a very strict molecular regulation infl uenced by internal and external factors. Tumor cells more and more disregard the regulations, and move into independency for a continuous proliferation, which has a very similar program in normal and tumor cells. The main route towards mitosis is the cell cycle, under the supervision of positive and negative regulators, forming checkpoints, telling to the cell - under the infl uence of mitogenic signals - to go or to stop. The most critical checkpoint is at the border of G1 and S phases where the main players are cyclinD, CDK4/6 and RB1. It turned out that the best targets to inhibit cell proliferation are the CDKs, but this approach, when used unselected targets, was unsuccessful due to the toxicity. To improve the clinical results, the selection of CDK4/6 as a therapeutic target seems to fulfi l most of the hopes. Today three drugs are the most promising: palbociclib (with an acceptance by FDA and EMA to treat breast cancer patients), abemaciclib and ribociclib (underclinical trials). Now, most of the data concern breast cancer, especially the combinations of CDK4/6 inhibitors and endocrine therapy, but many other malignancies are studied (e.g. liposarcoma, mantel cell lymphoma, melanoma, renal cancer, lung cancer, pancreatic cancer, ovarian cancer, teratomas etc.). The key points are the side-effects, the most frequently observed is neutropenia, but so far it is managed without serious toxicity.]

Clinical Oncology

[The role of PET in clinical oncology]


[Positron emission tomography (PET) has earned an important role in clinical imaging, where it is used almost exclusively as hybrid modality such as PET/CT and PET/MR. The driving force behind the development of the method and the increasing clinical penetration of PET in the past two decades was clearly its use in Oncology. The most used tracer in PET is the 18 F-labeled fl uoro-deoxy-glucose (FDG). With the help of this molecule malignant tumors and their metastases, in which anaerobic glycolysis is typically increased, can be identifi ed with high sensitivity in the total body volume. However, FDG is not a tumor specifi c tracer, thus both false positivity and false negativity may occure which reduces the diagnostic accuracy. Indications of FDG PET studies in Oncology continuously evolved, owing to scientifi c publications, large scale national programs and even health-economic considerations. This publication describes the well-established indications of FDG PET/CT(MR) tests in cancer diagnostics and furthermore discusses more recent new PET tracers already being applied as well as those expected to be used in the future.]

Clinical Oncology


A szerkesztők

Clinical Oncology

[Treatment of neuroendocrine tumors]


[Recently, the therapeutic possibilities for the locally invasive or metastatic neuroendocrine tumors developed signifi cantly, although we have no widely accepted predictive or prognostic factors, which could help to design the most effective sequential therapy. To make therapeutic strategy the internationally accepted clinical guidelines should be considered. The therapeutic activity has to be performed in oncological centers with the support of a multidisciplinary team.]

Clinical Oncology

[Gene modifi ed T cell therapy for patients with cancer]


[T cells genetically modifi ed to express chimeric antigen receptors can combine the antigen specifi city of monoclonal antibodies with the cytotoxic function, active biodistribution and long term persistence of T cells. The approach can induce 90% complete remission rate in patients with CD19+ lymphoid leukemias; however, the in patients with solid tumors the antitumor effi cacy of CAR T cells have not reached similar levels yet. The increased levels of interleukin-6 due to T cell activation play key roles in the majority of side effects and using anti-IL-6 monoclonal antibody, tocilizumab can effectively treat these complications. Novel gene modifi cation strategies and improvements in CAR T cell manufacturing, the approach has the potential to fundamentally change the way patients with cancer are treated in the not too distant future.]

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Lege Artis Medicinae

[Therapeutic strategies in rheumatoid arthritis]


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Clinical Oncology

[Treatment of head and neck cancer]


[Head and neck cancers cause worldwide a signifi cant problem in health care systems. Despite great advances in therapeutic modalities its prognosis has not changed in the past few decades. It is mainly caused by classical risk factors, like alcohol consumption and smoking, but in a signifi cant number of oropharyngeal cancers HPV infection plays a major role, which is associated with a new patient group characterized by a much better prognosis and therapeutic response. In the diagnostic phase staging examinations (CT scan, MRI, FDG-PET) are also involved which are necessary to multidisciplinary decision making. It can be largely infl uenced by the patient’s preference. The therapy is based on multimodality approach; surgery, radiotherapy, chemoirradiation, chemotherapy and the combination of these are used in early or locally advanced tumours. Targeted agents like EGFR inhibitors are partly used in the recurrent/metastatic setting or in combination with radiotherapy. Immun checkpoint inhibitors are new therapeutic options for pretreated, recurrent/metastatic patients and their role is under investigation in earlier therapeutic lines. Several clinical trials aim treatment desintensifi cation strategies in HPV positive tumours. Molecular genetic tests try to defi ne subgroups of patients to plan individualized treatment. Regarding the signifi cant functional and aesthetic damage of both disease and treatment, supportive care and rehabilitation are of great importance.]

Hypertension and nephrology

[Is there a role of triple combination in the therapy of hypertension? - Antihypertensive efficiency of perindopril-amlodipine-indapamide]

PÁLL Dénes, SZÁNTÓ Ildikó, PARAGH György, KATONA Éva

[Blood pressure reduction to target level decreases cardiovascular morbidity and mortality. However, in the vast majority of cases, this can be achieved only with a (multiple) combination regimen. The primary objective of the PAINT (Perindopril- Amlodipine plus Indapamide Combination for Controlled Hypertension Non-intervention Trial) study was to evaluate the efficacy of combination therapy with perindopril, amlodipine, and indapamide in patients who had not reached target blood pressure with their pre-existing therapy. Secondary objectives included the monitoring of metabolic parameters and the number of antihypertensive tablets taken by the subjects. In this subgroup-analysis we involved 126 patients (74 females and 52 males, mean age 59.8±12.5 years) who had a valid 24-hour ambulatory blood pressure monitoring both at baseline and at the end of the 4-months follow-up. At the beginning of the study none of the subjects reached blood pressure target despite taking on average 2.4±1.4 antihypertensive drugs. During the study, the subjects received the combination of amlodipine, perindopril, and indapamide instead of their pre-existing antihypertensive regimen. 24-hour mean systolic blood pressure decreased from 139.2±13.4 mmHg to 126.5±12.9 mmHg (p<0.01), as well as mean diastolic blood pressure from 77.3±11.3 mmHg to 71.1±8.7 mmHg (p<0.01). Heart rate remained unchanged. Blood pressure reduction was statistically significant both during the day and the night. We found significant blood pressure reduction in all hours (10.1-15.4/5.1-7.8 mmHg; p<0.001). Hyperbaric impact decreased from 366.9±251.1 mmHg × hour to 166.2±185.4 mmHg × hour (p<0.01) for systolic blood pressure, and from 112±130.6 mmHg × hour to 41.6±65.6 mmHg × hour (p<0.01) for diastolic blood pressure. We also could observe favourable changes in metabolic parameters, not only in lipids, but also in blood sugar level. The mean number of tablets taken by the subjects increased from 2.4 to 2.9, but this led to a significantly improved control of blood pressure. Triple combinations of state-of-the-art antihypertensive agents - such as of perindopril, amlodipine and indapamide - ensure effective blood pressure control in sufficiently compliant patients.]

Clinical Oncology

[Follicular lymphoma - a way to personalized and targeted therapy ]


[Although follicular lymphoma is the most frequent non-Hodgkin’s lymphoma with an indolent clinical course, it is a rare disease. Patients with FL are characterized with a long survival with a relatively good quality of life, however using the current standard chemo-immunotherapy, the disease is considered incurable. The increasing knowledge of the molecular genetic background of the disease and the role of the reactive microenvironment lead to a better understanding of the pathogenesis of follicular lymphoma. Furthermore, the detailed functional characterization of the various cell surface antigens and deciphering the complex network of signaling pathways catalyzed the development of a number of novel targeted therapies (monoclonal antibodies, kinase- and NFκB-inhibitors), while understanding the effects of the cell surface receptors of cytotoxic T-cells initiated development of the monoclonal checkpoint inhibitors. The epigenetic therapies represent a novel therapeutic area with methyltransferase inhibitors demonstrating the most favorable results. Among the novel therapies, the immunomodulatory lenalidomide appears as the most promising and most effective drug, which acts via regulating the microenvironment, and in combination with rituximab in fi rst line setting it demonstrated similar effi cacy to the current standard protocols. Indeed, the rational use of the novel data and drugs paves the way towards personalized and targeted therapies for FL, resulting in more effective treatment and further improvement in patients’ survival, with a very long disease-free survival representing cure.]