The role of neuromuscular ultrasound in diagnostics of peripheral neuropathies induced by cytostatic agents or immunotherapies.

A relevant number of cancer patients who receive potentially neurotoxic cytostatic agents develop a chemotherapy-induced peripheral neuropathy over time. Moreover, the increasing use of immunotherapies and targeted agents leads to a raising awareness of treatment-associated peripheral neurotoxicity, e.g., axonal and demyelinating neuropathies such as Guillain-Barré-like syndromes. To date, the differentiation of these phenomena from concurrent neurological co-morbidities or (para-)neoplastic nerve affection as well as their longitudinal monitoring remain challenging. Neuromuscular ultrasound (NMUS) is an established diagnostic tool for peripheral neuropathies. Performed by specialized neurologists, it completes clinical and neurophysiological diagnostics especially in differentiation of axonal and demyelinating neuropathies. No generally approved biomarkers of treatment-induced peripheral neurotoxicity have been established so far. NMUS might significantly extend the repertoire of diagnostic and neuromonitoring methods in this growing patient group in short term. In this article, we present enlargements of the dorsal roots both in cytostatic and in immunotherapy-induced neurotoxicity for the first time. We discuss related literature regarding new integrative applications of NMUS for cancer patients by reference to two representative case studies. Moreover, we demonstrate the integration of NMUS in a diagnostic algorithm for suspected peripheral neurotoxicity independently of a certain cancer treatment regimen emphasizing the emerging potential of NMUS for clinical routine in this interdisciplinary field and prospective clinical trials.

Applications of the Grading Scales for the Detection of Ototoxicity in Children after Treatment of Neuroblastoma and Extracranial Germinal Tumor.

INTRODUCTION: Advances in treatment have resulted in a significant increase in survival rates for patients cured of malignant diseases such as neuroblastoma (NBL) and extracranial germ cell tumor (GCT). NBL is one of the pediatric cancers during which potentially ototoxic cytostatic drugs (cisplatin and carboplatin) are used for treatment. Other cancers include germinal tumors, hepatoblastoma, sarcomas, and brain tumors. Often, this very aggressive treatment has a high risk of causing long-term side effects, including hearing loss. Hence, the present study aimed to evaluate the usefulness of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Brock, Chang, and International Society of Pediatric Oncology (SIOP) Boston scales in terms of detecting the high-frequency nature of hearing loss induced by ototoxic drugs and monitoring hearing status in children after completion of oncological treatment. Additionally, the frequency of hearing loss in children treated for NBL and extracranial GCT was assessed, and the principles of monitoring hearing in these patients were indicated. METHODS: The study group consisted of 78 patients diagnosed with NBL (n = 47) and GCT (n = 31). There were 23 boys and 24 girls in the NBL group, aged 0-16 years, and 21 boys and 10 girls in the GCT group, aged 0-18 years. The control group consisted of 54 patients who had never received oncological treatment, were not taking potentially ototoxic drugs, and appeared socially efficient in the subjective audiological assessment. Audiometric examinations and DP-acoustic otoemission measurements were performed. Additionally, impedance audiometry tests were done to exclude a possible conductive component of the hearing loss. RESULTS: The analysis shows that ototoxicity-induced hearing loss was observed in 13.8-65.5% of children. 75.9% of patients showed hearing loss in the 16 kHz frequency range, and at least 56.8% of patients showed hearing loss in the frequency range above 12.5 kHz. Hearing impairment, relevant to speech understanding, was displayed by more than 40% of children treated for NBL and GCT. CONCLUSIONS: The confirmation of hearing loss in nearly 65% of cases in both patients indicates the necessity to monitor the long-term side effects of anticancer treatment. Acoustic otoemission measurements, the adoption of articulatory indices based on an audiogram, or the use of arbitrary ototoxicity assessment scales such as Brock, Chang, or SIOP Boston are fully justified techniques for studying ototoxicity induced by cytostatic drugs. However, they all require continuous improvement to increase their sensitivity and specificity, especially in the pediatric group.

Evaluation of membrane-destructive processes in rats with induced carcinogenesis of the colon using the cytostatic vincristine.

Background: Every year the number of cases of colorectal cancer increases. Chemotherapy is one of the main methods of treating cancer. However, chemotherapeutic treatment of colorectal cancer is inextricably linked to hepatotoxic reactions. Objective: The aim of this study was to investigate the effect of the cytostatic vincristine on the background of previous enterosorption correction with the drug aut-m in adenocarcinoma of the colon. Material and methods: To simulate carcinogenesis, dimethylhydrazine (DMH) was administered subcutaneously to 77 rats for 30 weeks at a dose of 7.2 mg/kg body weight. After simulation of colon cancer, the animals were intragastricly administered entorosorbent at a dose of 1 ml of suspension (corresponding to 0.2 g of net weight of the drug) per 100 g of body weight of the animal, daily for 21 days. After detoxification therapy, rats with simulated carcinogenesis were administered the daily cytostatic vincristine at a dose of 0.23 mg/kg for 14 days. Results: It was found that prolonged administration of dimethylhydrazine is accompanied by destructive changes in plasma membranes, as evidenced by increased activity of enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and serum urea. Conclusions: The used sorbent aut-m showed an effective effect on reducing the manifestations of cytolytic processes in induced carcinogenesis, as indicated by the normalization of the studied parameters. The cytostatic vincristine, which was used in rats with induced colorectal cancer after enterosorption therapy, did not significantly affect the enhancement of cytolytic processes, which confirms the effectiveness of previous sorption measures under these conditions.

Cytostatic drugs and risk of genotoxicity in health workers. A literature review.

OBJECTIVE: To analyse the genotoxic risk of cytostatic drugs in health professionals after occupational exposure. METHOD: Literature was searched for the databases PubMed, Lilacs, The Cochrane Library and Scopus with free and controlled language (MeSH terms) using boolean operators AND and OR. The research was limited to articles published between 2005-2016. RESULTS: 11 articles were selected depending on their relevancy to this review's aim. Nine of the 11 articles proved the existence of damage to genetic material (DNA) of health workers, who were exposed to cytostatics. Furthermore, current security practices do not eliminate the chance of exposure completely. Therefore, the creation of new clinical trials is required. CONCLUSIONS: Handling cytostatic drugs can cause a genotoxic risk to health workers who are exposed to these substances. This exposure may cause damage on the workers' DNA. There are not enough data to prove a cause-effect relationship between the genotoxic risk and adverse reactions on individuals. Health education will be the main way to raise the awareness and prevention this problem.

The Angiotensin II Receptor Blocker Losartan Sensitizes Human Liver Cancer Cells to Lenvatinib-Mediated Cytostatic and Angiostatic Effects.

Molecular targeted therapy with lenvatinib is commonly offered to advanced hepatocellular carcinoma (HCC) patients, although it is often interrupted by adverse effects which require a reduction in the initial dose. Thus, an alternative lenvatinib-based therapy to compensate for dose reduction is anticipated. This study aimed to assess the effect of combination of low-dose of lenvatinib and the angiotensin-II (AT-II) receptor blocker losartan on human HCC cell growth. In vitro studies found that losartan suppressed the proliferation by inducing G1 arrest and caused apoptosis as indicated by the cleavage of caspase-3 in AT-II-stimulated HCC cell lines (Huh-7, HLE, and JHH-6). Losartan attenuated the AT-II-stimulated production of vascular endothelial growth factor-A (VEGF-A) and interleukin-8 and suppressed lenvatinib-mediated autocrine VEGF-A production in HCC cells. Moreover, it directly inhibited VEGF-mediated endothelial cell growth. Notably, the combination of lenvatinib and losartan augmented the cytostatic and angiostatic effects of the former at a low-dose, reaching those achieved with a conventional dose. Correspondingly, a HCC tumor xenograft assay showed that the oral administration of losartan combined with lenvatinib reduced the subcutaneous tumor burden and intratumor vascularization in BALB/c nude mice. These findings support that this regimen could be a viable option for patients intolerant to standard lenvatinib dosage.

Current Possibilities of Early Detection of Cardiotoxicity of Cytostatic Treatment.

BACKGROUND: Due to growing long-term survival rate of oncologic patients, there is increased interest in cardiotoxicity of oncologic treatment among medical professionals. It is concerning both paediatric and adult patients. When prescribing oncologic treatment, there should be focus on the efficacy and safety of the used drugs. Nowadays, the main problem is early dia-gnosis of cardiotoxicity. PURPOSE: In our work we wanted to investigate whether the increase in bio-markers after the cytostatic therapy with anthracyclines can predict further increase in the left ventricular volume and decrease of the left ventricular ejection fraction. MATERIALS AND METHODS: We were monitoring 36 patients with the dia-gnosis of non-Hodgkins lymphoma who received therapy with anthracyclines. After the therapy we were measuring the cardiac bio-markers NT-proBNP and high-sensitivity troponin I and performed echocardiography. RESULTS: In our group of patients there is a statistically significant correlation between increased levels of troponin I, NT-proBNP and increment of the left ventricular volume measured before the treatment and 3 months after the treatment. There is also a significant inverse correlation between the left ventricular volume and left ventricular ejection fraction. There was no relationship between higher cumulative doses of anthracyclines and the increment of the left ventricular volume. There is a significant correlation between higher cumulative doses of anthracyclines and higher levels of troponin I. CONCLUSION: The measurement of bio-markers troponin I and NT-proBNP should be considered for an early dia-gnosis of cardiotoxicity in oncologic patients. Echocardiography is also beneficial for the dia-gnosis in these patients. All efforts after the dia-gnosis should be focused on the therapy with cardioprotective drugs, which can prevent the development of severe heart failure.

Measures to prevent the risks associated with exposure to cytostatic drugs in glaucoma filtering surgery. / Medidas para prevenir los riesgos asociados con la exposición a citostáticos en cirugía filtrante de glaucoma.

INTRODUCTION: The use of cytostatic drugs such as Mitomycin C and 5-Fluorouracil is well-known in glaucoma filtering surgery, as well as the management of its complications. However, there is a lack of information regarding the preventive measures to be taken by the professional that handles these types of substances. OBJECTIVE: Raise awareness among professionals of the risks associated with the use of cytostatic drugs without adequate prevention measures. RESULTS: Review of the available literature and legislation on preventive measures in the management of cytostatic drugs in the medical and ophthalmological field. CONCLUSIONS: The prevention and awareness of the risks of the qualified professionals that handle these substances is the most important measure to prevent the possible risks. Coordination is necessary with the Occupational Health teams of the Hospital, as well as the professionals and staff involved in the different phases of the process, from the preparation in Hospital Pharmacy to its elimination.

Occupational exposure to cytostatic fumes during hyperthermic intraperitoneal chemotherapy.

Hyperthermic intraperitoneal chemotherapy (HIPEC)-heated, intra-abdominal chemotherapy-has become the treatment of choice for treating peritoneal metastases from ovarian, stomach or colorectal cancers. HIPEC has several advantages and disadvantages. The major benefit is minimal systemic toxicity for the patient, but there is a risk of occupational exposure for operating room staff. We have not found any reports of workers with chronic aplastic anaemia as a result of exposure to cytostatic fumes during HIPEC. The aim of this case report is to raise the awareness of potential negative health effects of inhalation exposure to cytostatic drugs. We present a rare case of a 43-year-old woman, suffering from aplastic anaemia as a long-term consequence of exposure to cytostatics. During the HIPEC procedure, surgical revision of the peritoneal cavity was undertaken which resulted in release of cytostatic fumes. Despite awareness of the health effects of occupational exposure to cytostatic drugs and well-developed procedures for safely handling them, unexpected exposure may occur causing serious medical conditions. These may develop in sensitive subjects although accidental high-level exposure may lead to unexpected long-term consequences in all workers. Medical staff need to be informed of the risks of HIPEC and safety guidelines to reduce the risk of exposure.

Cytostatics as hazardous chemicals in healthcare workers' environment.

Cytostatics not only induce significant side-effects in patients treated oncologically but also pose a threat to the health of occupationally exposed healthcare workers: pharmacists, physicians, nurses and other personnel. Since the 1970s numerous reports from various countries have documented the contamination of working areas with cytostatics and the presence of drugs/metabolites in the urine or blood of healthcare employees, which directly indicates the occurrence of occupational exposure to these drugs. In Poland the significant scale of occupational exposure to cytostatics is also confirmed by the data collected in the central register of occupational carcinogens/mutagens kept by the Nofer Institute of Occupational Medicine. The assessment of occupational exposure to cytostatics and health risks constitutes employers' obligation. Unfortunately, the assessment of occupational risk resulting from exposure to cytostatics raises a number of concerns. Provisions governing the problem of workers' health protection are not unequivocal because they derive from a variety of law areas, especially in a matter of hazard classification and safety data sheets for cytostatics. Moreover, no legally binding occupational exposure limits have been set for cytostatics or their active compounds, and analytical methods for these substances airborne and biological concentrations are lacking. Consequently, the correct assessment of occupational exposure to cytostatics, the evaluation of health hazards and the development of the proper preventive strategy appear difficult. The authors of this article described and discussed the amendments to the European provisions concerning chemicals in the light of employers' obligations in the field of employees' heath protection against the consequences of exposure to cytostatics. Some modifications aimed at a more effective health protection of workers occupationally exposed to cytostatics were also proposed. Int J Occup Med Environ Health. 2019;32(2):141-59.

Neutropenia inducida por citostáticos en oncología / Neutropenia induced by cytostatics in oncology

Se realizó un estudio descriptivo y transversal de 330 pacientes con cáncer, atendidos en el Hospital Oncológico Conrado Benítez de Santiago de Cuba, desde junio hasta diciembre del 2014, para determinar la presencia de neutropenias inducidas por quimioterapia. Presentaron esa afección 145 pacientes (44,0 por ciento). Predominaron el grupo etario de 41-60 años (51,0 por ciento), el sexo femenino (87,5 por ciento), el cáncer de mama (64,8 por ciento), el estadio clínico II (50,3 por ciento), los afectados con 2 episodios de neutropenia (62,1 por ciento), así como los grados leve (51,7 por ciento) y moderado (37,9 por ciento). Respondieron al tratamiento con ior® LeukoCIM 118 pacientes (81,4 por ciento). No se estableció asociación entre las diferentes combinaciones de citostáticos, el número de episodios y los grados de esa enfermedad. La disponibilidad del ior® LeukoCIM para tratar dicha afección facilitará su uso profiláctico y mejorará la calidad de vida de estos pacientes

A descriptive and cross-sectional study of 330 patients with cancer, assisted in Conrado Benítez Oncological Hospital in Santiago de Cuba, was carried out from June to December, 2014, to determine the presence of neutropenias induced by chemotherapy. This disorder was present in 145 patients (44.0 percent). There was a prevalence of the 41-60 age group (51.0 percent), female sex (87.5 percent), breast cancer (64.8 percent), clinical stage II (50.3 percent), those affected patients with 2 neutropenia episodes (62.1 percent), as well as light (51.7 percent) and moderate grades (37.9 percent). One hundred eighteen patients responded to the treatment with ior® LeukoCIM (81.4 percent). There was no association between the different combinations of cytostatics, number of episodes and grades of that disease. The availability of the ior® LeukoCIM to treat this disorder will facilitate its prophylactic use and will improve these patients life quality

Reactions to cytostatic agents in children.

PURPOSE OF REVIEW: The current review will focus on drug hypersensitivity reactions to chemotherapy specifically to those drugs most used in children. We know that potentially all chemotherapeutic agents can cause infusion reactions, generally defined as adverse drug reactions. Of these, some are Type A, defined as expected and described in the characteristics of the drug and others, and Type B, defined as unexpected reactions which cannot be explained by the known toxicity profile of the drug. When an unexpected reaction occurs, drugs we can refer as hypersensitivity reactions (HSRs). Some of these (HSRs) are allergic reactions as they have an underlying immunologic mechanism. In general, the cytotoxic agents most commonly associated with HSRs are the platinum salts derivatives, taxanes, pegylated liposomal doxorubicin, L-asparaginase, procarbazine, etoposide, bleomycin, and cytarabin. RECENT FINDINGS: HSRs may also occur in children with cancer, during the treatment with chemotherapeutic drugs. The most used drugs of this group in children to cause HSRs are: carboplatin, L-asparaginase, and methothrexate. The aim of this review is to summarize the incidence and the clinical features of HSRs occurring with these drugs in children. SUMMARY: The aim of this review is to summarize the incidence and the clinical features of HSRs occurring with these drugs in children. The current review will focus on the most involved drugs in children, the type of reactions, the mechanisms involved, and the best way to manage them.

Extravasación de citostáticos por vía periférica. tratamiento quirúrgico: ¿cuándo y cómo? / Extravasation of peripheral cytostatic. surgical treatment: when and how?

Se analiza el tratamiento quirúrgico en las extravasaciones de citostáticos por vía periférica. Se discute cuándo y cómo realizarlo. Se lo ubica dentro del contexto de los otros dos tratamientos: el de urgencia y el clínico. Se señala que el tipo de citostático utilizado y el estado clínico de paciente influyen en esta decisión.

Surgical treatment in peripheral cytostatic extravasations is analysed. It discusses when and how to perform it. It is placed within the context of the other two treatments: the emergency and the clinical. It is pointed out that the type of cytostatic used and the clinical status of the patient influence this decision.

Magnetic field therapy in patients with cytostatics-induced polyneuropathy: A prospective randomized placebo-controlled phase-III study.

No causal treatment for chemotherapy-induced peripheral neuropathy (CIPN) is known. Therefore, there is an urgent need to develop a therapy for CIPN. Only scarce clinical data are available concerning magnetic field therapy (MFT) in this context. We conducted a unicentric, randomized, double-blind, placebo-controlled phase-III trial of an MFT device versus placebo. In this study, we randomized 44 patients with CIPN to two treatment groups, where 21 patients were treated with MFT (Group 1) and 23 patients received placebo (Group 2). We evaluated the efficacy of MFT at baseline (T1 ), after 3 weeks of study treatment (T2 ), and after 3 months of study treatment (T3 ). The primary endpoint was nerve conduction velocity (NCV), while secondary endpoints were the Common Toxicity Criteria (CTCAE) score and the Pain Detect End Score at T3 . Seventeen of the patients in Group 1 and 14 patients in Group 2 completed the respective study treatment. The primary endpoint, significant improvement of NCV at T3 , was achieved by MFT (P = 0.015), particularly for sensory neurotoxicity of the peroneal nerve. Also, in respect to the secondary endpoints, significant improvement (P = 0.04) was achieved in terms of the patients' subjectively perceived neurotoxicity (CTCAE score), but not of neuropathic pain (P = 0.11). From data in the randomized study presented here, a positive effect on the reduction of neurotoxicity can be assumed for the MFT device. Patients with sensory neurotoxicity in the lower limbs, especially, should therefore be offered this therapy. Bioelectromagnetics. 38:85-94, 2017. © 2016 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.

Evidence of exposure to cytostatic drugs in healthcare staff: a review of recent literature.

OBJECTIVE: Provide updated evidence and learn about the actions that must be implemented in order to prevent the occupational exposure to cytostatic drugs. METHOD: A bibliographic search was carried out on the MEDLINE, COCHRANE PLUS and WEB OF SCIENCE databases, with the terms "surface contamination", "cytostatic drug", "drug preparation", "occupational exposure", "safe handling" and "closed-system transfer device", within the 2010-2015 period. RESULTS: Thirteen articles were selected for review. These articles are from hospitals in U.S.A., Canada, Japan, Australia, Spain, Portugal and Germany. In all of them, surface contamination by cytostatic agents was found in over 15 different surfaces, with concentrations ranging from 1.69 ng/cm2 to 4-784 µg/cm2. The specific drugs were cyclophosphamide, ifosfamide, 5-fluorouracil, methotrexate, paclitaxel, cisplatin, gemcitabine, and docetaxel. Closed-system transfer devices can reduce the contamination in work surfaces significantly, but do not eliminate it. CONCLUSIONS: Presence of contamination by cytostatic drugs was confirmed in many hospitals across all 5 continents. In all cases, contamination was found in the cabinet, on the floor in front of the cabinet, and in other places of the Hospital Pharmacy. The drug most frequently found was cyclophosphamide. The most effective action used to reduce contamination was the closed-system transfer devices (CSTDs).

Objetivo: Disponer de la evidencia mas actual y conocer las medidas a aplicar para evitar la exposicion laboral a citostaticos. Método: Se realizo una busqueda bibliografica en las bases de datos MEDLINE, COCHRANE PLUS y WEB OF SCIENCE con los terminos "surface contamination", "antineoplastic drug", "drug preparation", "occupational exposure", "safe handling" y "closed-system transfer device" para el periodo 2010- 2015. Resultados: Se seleccionaron 13 articulos para la revision. Estos articulos corresponden a hospitales de USA, Canada, Japon, Australia, Espana, Portugal y Alemania. En todos ellos se ha encontrado contaminacion por farmacos citostaticos en mas de 15 superficies distintas con concentraciones que van desde los 1,69 ng/cm2 hasta 4,784 µg/cm2. Los farmacos determinados han sido ciclofosfamida, ifosfamida, 5-fluorouracilo, metotrexato, paclitaxel, cisplatino, gemcitabina y docetaxel. El sistema cerrado reduce la contaminacion de las superficies de trabajo significativamente, pero no la elimina. Conclusiones: Se verifica la presencia de contaminacion por farmacos citostaticos en numerosos hospitales de los 5 continentes. En todos los casos se ha encontrado contaminacion en la cabina, en el suelo frente a la cabina y en otros lugares de la farmacia. El farmaco mas frecuentemente encontrado es la ciclofosfamida. El sistema empleado mas eficaz para reducir la contaminacion es el uso de dispositivos cerrados de transferencia (CSTD-closed system transfer device).

Instability Due to Drug-Induced Vestibulotoxicity.

OBJECTIVE: The therapeutic use of ototoxic drugs is relatively common, particularly in patients with severe diseases. It is likely that disturbances of balance in these patients are underestimated by clinicians. MATERIALS AND METHODS: The purpose of this study was to identify drugs involved in the vestibulotoxic origin of instability in a group of 18 patients. RESULTS: Six patients showed both cochlear and vestibular damage, while 12 were affected only by posterior labyrinthine damage. Four groups of drugs were identified: antibiotics (nine patients), cytostatics (four), anti-tuberculosis medicinal products (three), and other drugs (two). Cytostatics were involved in many cases studied, a fact scarcely reported before. CONCLUSION: It is important to ensure an early diagnosis to prevent ototoxic effects induced by drugs. We propose that patients receiving potential ototoxic drugs undergo cochlear and vestibular assessments. Further, we recommend that patients with instability undergo vestibular rehabilitation.

Bilberry extract, its major polyphenolic compounds, and the soy isoflavone genistein antagonize the cytostatic drug erlotinib in human epithelial cells.

Erlotinib (Tarceva®) is a chemotherapeutic drug approved for the treatment of pancreatic cancer and non-small cell lung cancer. Its primary mode of action is the inhibition of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK). Recently, RTK-inhibiting polyphenols have been reported to interact synergistically with erlotinib. Furthermore some anthocyanidins and anthocyanin-rich berry extracts have been reported to inhibit tyrosine kinases, including the EGFR, which raises the question of potential interactions with erlotinib. Polyphenol-rich preparations such as berry- or soy-based products are commercially available as food supplements. In the present study we tested a bilberry extract, its major anthocyanin and potential intestinal degradation products, as well as genistein, with respect to possible interactions with erlotinib. Cell growth inhibition was assessed using the sulforhodamine B assay, while interactions with EGFR phosphorylation were analyzed by SDS-PAGE/western blotting with subsequent immunodetection. Genistein, bilberry extract, delphinidin-3-O-glucoside and delphinidin were found to antagonize erlotinib whereas phloroglucinol aldehyde was found to enhance cytostatic effects of the drug on human epithelial A431 cells. Genistein also antagonized the EGFR inhibitory effects of erlotinib, whereas bilberry anthocyanins showed no significant interactions in this regard. Our data indicate that different polyphenols are potentially able to impair the cytostatic effect of erlotinib in vitro. Genistein interacts via the modulation of erlotinib-mediated EGFR inhibition whereas bilberry anthocyanins modulated the growth-inhibitory effect of erlotinib without affecting EGFR phosphorylation, thus indicating a different mechanism of interference.

[Study of cardiovascular morbidity in nurses exposed to cytostatic drugs: Multivaried approach analysis]. / Étude de la morbidité cardiovasculaire chez les infirmiers exposés aux cytostatiques : approche par l'analyse multivariée.

OBJECTIVE: To investigate the relationship between cardiovascular morbidity and exposure to cytostatic drugs. MATERIALS AND METHODS: A descriptive analytical study was conducted with 74 nurses exposed to cytostatic drugs in oncology and 215 unexposed. A medical questionnaire was applied. Exposure to cytostatic drugs was estimated by the exposure time and the index of cytostatic contact (ICC). The statistical tests used are: relative risk, odds ratio, multivariate analysis: descriptive (ACM) and predictive (AIC system). RESULTS: It is a young population; the average age is 42±9.9years with a female predominance (81%). The average length was 18.4±11.11years. The average of the ICC ranged from 0.60 to 12.6 with a highly significant difference. For morbidity, there was no difference for most cardiovascular disease (RR, 1.03; 95% CI [0.59; 1.82]) outside of hypertension and venous thrombosis. ACM objectified separation between the terms and the comments of the two groups for HTA. The interpretation of results at alpha=0.05 showed an association with cardiovascular disease. The study of the association between cardiovascular morbidity and exposure to cytostatic objectified association with seniority and the ICC with a statistically significant difference (P=0.01). CONCLUSION: Multivariate analysis helped to eliminate confounding factors and retain the ICC and length of exposure to cytostatic in the onset of cardiovascular morbidity.

Neutropenia febril postquimioterapia, Instituto de Oncología y Radiobiología / Febrile neutropenia after cytostatic therapy observed in the Institute of Oncology and Radiobiology

Objetivo: caracterizar a los pacientes oncológicos que presenten episodios de neutropenia febril postquimioterapia ingresados en el Instituto de Oncología y Radiobiología en el periodo de enero a mayo del 2015. Métodos: se realizó un estudio descriptivo de corte transversal a una muestra de 36 pacientes. Se revisaron las historias clínicas donde se tomaron las variables analizadas. Resultados: predominaron los pacientes del sexo femenino (61,1 por ciento). Dentro de las enfermedades oncológicas predominaron los pacientes con Linfomas no Hodgkin (25,0 por ciento) y los medicamentos citostáticos vinculados a la neutropenia fueron el carboplatino, paclitaxel, ifosfamida y etopósido. La recuperación hematológica se logró en la mayoría de los casos antes de las 72 horas y el mayor número de pacientes (72,2 por ciento) fueron clasificados como una neutropenia de bajo riesgo, según los criterios de la Multinational Association for Supportive Care. Conclusiones: en la muestra estudiada la neutropenia febril presenta un incremento proporcional con la edad y las enfermedades de origen hematopoyéticos, cuyos esquemas quimioterápicos consisten en altas dosis de agentes citostáticos(AU)

Objective: to characterize the oncological patients who present with post chemotherapy febrile neutropenia and were admitted to the Institute of Oncology and Radiobiology in the period of January to May, 2015. Methods: a descriptive cross-sectional study of a sample of 36 patients. Their medical histories were checked from which the analyzed variables were taken. Results: females predominated in the study (61,1 percent). Among the oncological diseases, non-Hodgkin lymphomas (25,0 percent) prevailed whereas the cytostatic drugs found related to neutropenia were carboplatin, paclitaxel, ifosfamide and etoposide. The hematological recovery was reached in most cases before 72 hours and a lot of patients (72, 2 percent) were classified as low risk neutropenia according to the Multinational Association for Supportive Care criteria. Conclusions: in the study sample, the febrile neutropenia increases with the age and with hematopoietic diseases whereas chemotherapy schemes are based on high dose cytostatic agents(AU)

Low frequency magnetic field therapy in patients with cytostatic-induced polyneuropathy: a phase II pilot study.

Cytostatic-induced polyneuropathy (CIPN) is a common and serious toxicity in tumor patients. Treatment and prophylactic measures are mainly ineffective. Therefore, there is an urgent need to establish a sufficient therapy for pPNP. Between July 2007 and August 2008, 20 patients were treated with low frequency (4-12 Hz) magnetic field therapy (MFT), and neurological examinations were conducted at the trial therapy's beginning, as well as after 3-4 weeks. Standardized testing methods were applied, i.e., the Common Toxicity Criteria questionnaire of the National Cancer Institute and the measurement of nerve conduction velocity (NCV) in the electrophysiological examination. In terms of the components sensory ataxia and neuropathy as well as neuropathic pain, an improvement was achieved using MFT. This effect was confirmed by an increase in NCV. Using low frequency MFT, CIPN was influenced positively on both hands and feet. This could represent a future therapy principle for these patients.

Selected attributes of polyphenols in targeting oxidative stress in cancer.

Various plant polyphenols have been recognized as redox active molecules. This review discusses some aspects of polyphenols' modes of redox action, corresponding structure-activity relationships and their potential to be applied as adjuvants to conventional cytostatic drugs. Polyphenols' antioxidative capacity has been discussed as the basis for targeting oxidative stress and, consequently, for their chemopreventive and anti-inflammatory activities, which may alleviate side-effects on normal cells arising from oxidative stress caused by cytostatics. Some polyphenols may scavenge various free radicals directly, and some of them are found to suppress free radical production through inhibiting NADPH oxidases and xanthine oxidase. Additionally, polyphenols may increase antioxidative defense in normal cells by increasing the activity of NRF2, transcription factor for many protective proteins. The activation of the NRF2-mediated signaling pathways in cancer cells results in chemoresistance. Luteolin, apigenin and chrysin reduce NRF2 expression and increase the chemosensitivity of cancer cells to cytostatic drugs. Their common 5,7-dihydroxy-4H-chromen-4-one moiety, may represent a starting pharmacophore model for designing novel, non-toxic compounds for overcoming chemoresistance. However, prooxidative activity of some polyphenols (quercetin, EGCG) may also provide a basis for their use as chemotherapeutic adjuvants since they may enhance cytotoxic effects of cytostatics selectively on cancer cells. However, considerable caution is needed in applying polyphenols to anticancer therapy, since their effects greatly depend on the applied dose, the cell type, exposure time and environmental conditions.