Clinical Oncology

[Tumor induction by chemotherapy]

APRIL 30, 2020

Clinical Oncology - 2020;7(02)

[Without chemotherapy, the fi ve-year survival rate of detected cancers would be between 0 and 15%, depending on the tumor, and between 17 and 85% with current therapy. Several warnings call attention to the dangers of chemotherapy-induced side effects, most notably the potential for tumor-inducing ability, which can affect 5-10% of patients who have recovered beyond fi ve years. Some systematically applied drugs used in chemotherapy (alkylating agents, etoposide, arsenic trioxide) are able to cause mutations in healthy cells of the patients, increasing the likelihood that the mutated cells will start a later (secondary) tumor formation. In addition to mutagenic effects, some chemotherapeutic agents exert their effects on normal myeloid and epithelial cells of the body, which, by altering the tissue microenvironment, create the potential for malignant transformation. Tumor-associated macrophages (TAMs), which can alter gene expression patterns by tumor cell secreted factors and promote the survival and invasiveness of tumor cells by pro-carcinogenic signals, are very important in this process. It is of utmost importance that doctors, pharmacists, technicians and nurses working with cancer-causing materials do not come into direct contact with dangerous substances and wear appropriate protective equipment.]



Further articles in this publication

Clinical Oncology

[Coronavirus pandemic – new challenges in oncotherapy]


[This review outlines some of the basic observations related to coronaviruses infecting animals and describes – in a nutshell – the characteristics of human coronaviruses causing mild or severe respiratory diseases in infected individuals. A special attention is given to SARS-CoV-2, the causative agent of the current coronavirus disease (Covid-19) pandemic, and to the pathomechanism of severe acute respiratory syndrome (SARS) which is also accompanied with multiorgan failure in a subset of infected patients. Recently discovered unique molecular features of SARS-CoV-2 are described as well. These molecular cues may affect human to human virus transmission whereas they are absent, remarkably, from the other lung-targeting highly pathogenic human coronaviruses (SARS-CoV-1 and MERS-CoV) which did not spread all over the world. The possibilities of active immunization to prevent SARS-CoV-2 infection and the development of selective small molecule inhibitors curbing the replication of the virus are also touched upon. The review closes with a few remarks regarding the Hungarian and international recommendations concerning the treatment of SARSCoV- 2 infected cancer patients.]

Clinical Oncology

[Immunotherapy of hepatocellular carcinoma]


[The systemic treatment of HCC was based exclusively on sorafenib near 10 years. In the past 2-3 years some new molecules demostrated their effectivites in phase III clinical trials. So the immuncheckpoint-inhibitors (ICI) demands their place in systemic treatment of HCC. Nivolumab and pembrolizumab are recommended already in second line in NCCN and ESMO clinical guidelines. Nivolumab demostrated his effectivity against the standard treatment sorafenib in a phase III clinical trial, although the results were not signifi cant. However, the combination treatment of atezolizumab and bevacizumab seems better than sorafenib in a phase III clinical trial, so the combination is recommended already in fi rst line in the NCCN guideline. There are more clinical trials with ICIs in progress as in monotherapy as in combination therapy with other modalities.]

Clinical Oncology

[Hormone replacement therapy in cancer survivors – Review of the literature]

DELI Tamás, OROSZ Mónika, JAKAB Attila

[Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insuffi ciency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women’s Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude defi nitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Yet, the oncologic risk of HRT is extremely diffi cult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies. We group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: ’HRT is advanageous’ (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); ’HRT is neutral’ (e.g. BRCA 1/2 mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); ’HRT is relatively contraindicated’ for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); ’HRT is diasadvantageous and thus contraindicated’ (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).]

Clinical Oncology

[Development and 10-year history of a biosimilar: the example of Binocrit®]


[Patent expirations for several biological products have prompted the development of alternative versions, termed ‘biosimilars’, which have comparable quality, safety and effi cacy to a licensed biological medicine (also referred to as the ‘reference’ medicine). The fi rst biosimilars developed in oncology were the supportive-care agents fi lgrastim and epoetin. Binocrit® (HX575) is a biosimilar version of epoetin alfa, indicated in the oncology setting for the treatment of chemotherapy-induced anemia (CIA). The process for development and approval of Binocrit® as a biosimilar included extensive analytical characterization and comparison with the reference epoetin alfa. This was followed by a clinical development program comprising phase I pharmacokinetic/pharmacodynamic studies to show bioequivalence to the reference medicine and a confi rmatory phase III study to confi rm therapeutic effectiveness in CIA. Since its approval, Binocrit® has been extensively used and studied in real-world clinical practice. The accumulated data confi rm that Binocrit® is an effective and well-tolerated option for the treatment of CIA in patients with cancer.]

Clinical Oncology

[Molecular residual tumor monitoring in solid cancers]

SZÁSZ A. Marcell, TOBIÁS Bálint, KÓSA János, LAKATOS Péter

[Blood-based diagnostics has long been used in the oncological practice of solid tumors, but its full potential is just unfolding recently. Quantitative measurement of tumor markers, circulating tumor cells, and some of their products or components have now become available and are part of a multimodal system that provides additive parameters in clinical decision making. The most challenging oncological questions can be answered by the detection, characterization and measurement of circulating free DNA (cfDNA), which, due to its growing importance, bears the potential of incorporation into routine practice. In this overview, we review the „blood impressions” of solid tumors and present the most promising results in different patient groups, especially in lung, breast, colon, and bladder tumors, which are also valid for other solid tumors.]

All articles in the issue

Related contents

Clinical Oncology

[Cancer-treatment induced peripheral neuropathy]


[Peripheral neuropathy is caused by structural or functional damage of nervous system. The pathophysiology is not well known. Its clinical features are established but there is a need to standardize CIPN assessment, also considering that health care providers and patients frequently have a different perception of CIPN severity. Neurotoxicity caused by traditional chemotherapy is widely recognized in patients with cancer. The adverse effects of newer therapeutics, such as targeting and immunotherapeutic agents, need more information for the proper management. This review addresses the main neurotoxicities of cancer treatments with a focus on the newer therapeutics. Recognition of these patterns of toxicity is important because drug discontinuation or dose adjustment might prevent further neurological injury. Treatment is symptomatic. For prevention or treatment there is need for further basic research outcomes.]

Clinical Neuroscience

[Temozolomide chemotherapy of patients with recurrent anaplastic astrocytomas and glioblastomas]


[Introduction - Anaplastic astrocytomas and glioblastomas are the most frequent and most malignant hemispherial tumours. Unfortunately, astrocytic tumours are of infiltrative character and radical removal is not possible. Recurrent malignant gliomas are rarely suitable for reoperation. In most of the cases of recurrent gliomas chemotherapy is the last choice. Patients and method - Seventy-five consecutive patients with recurrent malignant astrocytomas and glioblastomas had been treated at our institute with per os temozolomide for five days every month. The patients received two to 16 courses of chemotherapy. The toxicity, quality of life, response to chemotherapy and survival data were analysed. Results - Out of 75 patients four were excluded following the first treatment due to myelotoxicity, and allergic reactions. Among the patients treated with temozolomide in seven cases complete response, 17 partial response, 14 progressive disease were observed. In 33 cases the disease stabilized and out of them in 27% a significant neurological improvement was detected. The time to progression was 6.8 months and the median survival time 8.75 months for patients with glioblastoma and with malignant astrocytoma or malignant mixed oligoastrocytoma 9.45 and 11.15 months, respectively. The overall survival for patients with originally lower grade glioma was 70.32 and for patients with glioblastoma multiforme 17.43 months. Conclusions - Temozolomide chemotherapy in patients with recurrent malignant astrocytoma and glioblastoma proved to be efficacious and similar good results were achieved as with a nitrosourea based combined chemotherapy. Even in those patients who received previous chemotherapy temozolomide is well tolerated and a relatively long time to progression was achieved in cases of recurrent malignant gliomas. In a few number of patients where BCNU had been previously failed with temozolomide stable disease was achieved. Temozolomide seems to be a promising drug in the chemotherapy of malignant gliomas and can be applied as a second line chemotherapy, as well.]

Clinical Oncology

[Neoadjuvant treatment of rectal cancer]


[Rectal cancer due to its frequent local invasion, high recurrence rate and metastatic potential is a serious health problem, leading to decreased life quality, severe complaints and death. Treatment for locally advanced, resectable rectal cancer improved over the years. Various chemotherapy protocols and combinations with radiation therapy and radical surgery - total mesorectal excision (TMA) - are the main elements of current therapy. Preoperative combined chemoradiation followed by surgery is the preferred treatment sequence. Radiation treatment in combination with fl uoropyrimidines (infusional 5-fl uorouracil [5-FU] or oral capecitabine) is recommended. Clinical trials with oxaliplatin-based neoadjuvant chemoradiation did not improve the pathologic complete response rate (pCR). Oxaliplatin-based treatment was more toxic as compared with 5-FU. The data concerning local recurrence rate and survival are controversial. Adjuvant chemotherapy in some studies improved survival, so - based on positive results in colon cancer - adjuvant FOLFOX chemotherapy may be recommended.]

Clinical Oncology

[Oncological management of gastro-entero-pancreatic neuroendocrine neoplasias]


[Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are unusual and relatively rare neoplasms. They characteristically synthetize, store and secrete a variety of peptides and neuroamines, which can lead to development of disctinct clinical syndromes. Clinical symptoms and presentations vary depending on the location and hormones produced by the tumor. The diagnosis of NETs is established by histological examination and the immunohistochemical detection of general neuroendocrine markers, such as chromogranin A (CgA) and synaptophysin. An update of the WHO classifi cation has resulted in a new classifi cation dividing neuroendocrine neoplasms into neuroendocrine tumors (NETs) including G1 (Ki67 index ≤2%) and G2 (Ki67 index 3-20%) tumors and neuroendocrine carcinomas (NECs) with Ki67 index >20%, G3. The different available therapeutic approaches, including surgery, liver-directed ablative therapies, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, are discussed in this overview.]

Clinical Oncology

[Recent strategies in the chemoterapy of soft tissue tumors]

PÁPAI Zsuzsanna, KISS Nóra

[Conventional adjuvant therapy is, in most cases, either the well-known standard doxorubicin monotherapy or the combination of doxorubicin + ifosfamide. No clear guideline has been developed yet - adjuvant therapy is recommended in cases with high grade, larger than 10 cm, sarcoma, where surgery hasn’t been suffi ciently radical, and adjuvant radiotherapy may not be advisable. In locally advanced tumors, due to the requirements of limb salvage, isolated limb perfusion is recommended. As a new compound, hafnium-oxide nanoparticles (NBTXR3) can be useful in local therapy: combining intratumoral injection and radiotherapy may be a fl agship initiative, however further investigations are necessary. In the treatment of metastatic tumors, beside the standard methods, new, targeted treatments are becoming more and more prevalent: in leiomyosarcomas trabectedine, pazopanib and olaratumab; in liposarcomas trabectedine and eribulin; in synovial sarcomas pazopanib; and in imatinib-resistant GIST, sunitinib and regorafenib. Soft tissue sarcomas are rare tumors categorized as heterogeneous histological subtypes. In their treatment, it is key to customize the treatment based on these subtypes and interdisciplinary collaboration with the orthopedic surgeon, the pathologist and the radiotherapist to determine the suitable therapy for each individual.]