RESUMO
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.
Assuntos
Antineoplásicos , Citostáticos , Surdez , Perda Auditiva , Neuroblastoma , Ototoxicidade , Masculino , Feminino , Humanos , Criança , Antineoplásicos/efeitos adversos , Citostáticos/efeitos adversos , Ototoxicidade/diagnóstico , Ototoxicidade/etiologia , Cisplatino/efeitos adversos , Perda Auditiva/induzido quimicamente , Perda Auditiva/diagnóstico , Neuroblastoma/tratamento farmacológico , Neuroblastoma/induzido quimicamenteRESUMO
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.
Assuntos
Neoplasias do Colo , Citostáticos , 1,2-Dimetilidrazina/toxicidade , Animais , Peso Corporal , Carcinogênese/induzido quimicamente , Carcinógenos/toxicidade , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Citostáticos/efeitos adversos , Humanos , Ratos , Vincristina/efeitos adversosRESUMO
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.
Assuntos
Anemia Aplástica/induzido quimicamente , Citostáticos/efeitos adversos , Hipertermia Induzida/enfermagem , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Adulto , Feminino , HumanosRESUMO
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.
Assuntos
Citostáticos/efeitos adversos , Magnetoterapia , Polineuropatias/induzido quimicamente , Polineuropatias/terapia , Adulto , Idoso , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: In head-to-head comparisons of coronary drug-eluting stents, the primary endpoint is traditionally assessed after 9-12 months. However, the optimum timepoint for this assessment remains unclear. In this study, we assessed clinical outcomes at up to 5 years' follow-up in patients who received two different types of drug-eluting stents. METHODS: We undertook this multicentre, open-label, randomised superiority trial at five percutaneous coronary intervention centres in Denmark. We randomly allocated 2332 eligible adult patients (≥18 years of age) with an indication for drug-eluting stent implantation to the zotarolimus-eluting Endeavor Sprint stent (Medtronic, Santa Rosa, CA, USA) or the sirolimus-eluting Cypher Select Plus stent (Cordis, Johnson & Johnson, Warren, NJ, USA). Randomisation of participants was achieved by computer-generated block randomisation and a telephone allocation service. The primary endpoint of the SORT OUT III study was a composite of major adverse cardiac events-cardiac death, myocardial infarction, and target vessel revascularisation-at 9 months' follow-up. In this study, endpoints included the occurrence of major adverse cardiac events and definite stent thrombosis at follow-up times of up to 5 years. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00660478. FINDINGS: We randomly allocated 1162 patients to receive the zotarolimus-eluting stent and 1170 to the sirolimus-eluting stent. At 5-year follow-up, rates of major adverse cardiac events were similar in patients treated with both types of stents (zotarolimus-eluting stents 197/1162 [17.0%] vs sirolimus-eluting stents 182/1170 [15.6%]; odds ratio [OR] 1.10, 95% CI 0.88-1.37; p=0.40). This finding was indicative of the directly contrasting results for rates of major adverse cardiac events at 1-year follow up (zotarolimus 93/1162 [8.0%] vs sirolimus 46/1170 [3.9%]; OR 2.13, 95% CI 1.48-3.07; p<0.0001) compared with those at follow-up between 1 and 5 years (104 [9.0%] vs 136 [11.6%]; OR 0.78, 95% CI 0.59-1.02; p=0.071). At 1-year follow-up, definite stent thrombosis was more frequent after implantation of the zotarolimus-eluting stent (13/1162 [1.1%]) than the sirolimus-eluting stent (4/1170 [0.3%]; OR 3.34, 95% CI 1.08-10.3; p=0.036), whereas the opposite finding was recorded for between 1 and 5 years' follow-up (zotarolimus-eluting stent 1/1162 [0.1%] vs sirolimus-eluting stent 21/1170 [1.8%], OR 0.05, 95% CI 0.01-0.36; p=0.003). 26 of 88 (30%) target lesion revascularisations in the zotarolimus-eluting stent group occurred between 1 and 5 years' follow-up, whereas 54 of 70 (77%) of those in the sirolimus-eluting stent group occurred during this follow-up period. INTERPRETATION: The superiority of sirolimus-eluting stents compared with zotarolimus-eluting stents at 1-year follow-up was lost after 5 years. The traditional 1-year primary endpoint assessment therefore might be insufficient to predict 5-year clinical outcomes in patients treated with coronary drug-eluting stent implantation. FUNDING: Cordis and Medtronic.
Assuntos
Citostáticos/administração & dosagem , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Sirolimo/análogos & derivados , Sirolimo/administração & dosagem , Idoso , Doença da Artéria Coronariana/terapia , Reestenose Coronária/prevenção & controle , Trombose Coronária/etiologia , Citostáticos/efeitos adversos , Citostáticos/uso terapêutico , Stents Farmacológicos/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Projetos de Pesquisa , Método Simples-Cego , Sirolimo/efeitos adversos , Sirolimo/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Citostáticos/efeitos adversos , Magnetoterapia , Polineuropatias/induzido quimicamente , Polineuropatias/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
AIM: To evaluate the impact of anti-B-cell therapy on the clinical and immunological parameters of systemic lupus erythematosus (SLE) activity, on the time course of changes in these parameters during long-term follow-up, and on the tolerability of repeated rituximab (RTM) therapy cycles. SUBJECTS AND METHODS: RTM was given to 97 patients with high activity of SLE refractory to treatment with glucocorticosteroids (GCS) and cytostatics. The follow-up lasted 18 (12-36) months. The most common clinical manifestations of SLE were lupus nephritis (LN) (62%) and skin (33%) and nervous system (22.7%) involvements. Clinical SLE activity was assessed applying the SLE disease activity index 2000 (SLEDAI2K); therapeutic effectiveness was evaluated using indicators, such as partial response (PR), complete response (CR) and exacerbation. The exacerbation was classified as moderate and severe using the Selena-Sledai Flare index (SFI). RESULTS: Depletion was identified in 78% of the patients with SLE immediately after RTM therapy. During 3.5 years of follow-up, the effect of RTM was seen in 82% of the patients after repeated RMT therapy cycles (CR 56% and PR 28%). Exacerbations were observed in a total of 24 (24.7%) patients; the exacerbation lasted 12 (12-24) months after RTM therapy: of them 17.5% with LN and 7.2% with extrahepatic manifestations of SLE (exacerbations occurred 12 (12-24) and 18 (6-48) months after RMT therapy). In 24 exacerbated patients, B cells recovered at 6 (3-12) months. A year after RMT therapy, a group of 35 patients who were observed to have complete B cell depletion achieved CR statistically significantly more frequently than a group of 20 patients who had B-cell recovery (65.7 and 30% respectively, p = 0.03). CR was observed significantly more often in patients after repeated RTM therapy cycles than those who had received only one RTM therapy cycle (p = 0.02). The long-term follow-up showed a reduction in SLEDAI2K, normalization of laboratory values, and a decrease in the daily dose of GCS. Most patients tolerated well both the first and repeated RTM therapy cycles. CONCLUSION: According to the results of the long-term follow-up, RTM therapy is a highly effective treatment option for SLE patients in whom the previous standard therapy with GCS and cytostatics was previously ineffective. The 3.5-year follow-up showed a good tolerability of RTM and revealed no increase in the risk of infectious complications or adverse reactions.
Assuntos
Anticorpos Monoclonais Murinos , Lúpus Eritematoso Sistêmico , Adulto , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Citostáticos/administração & dosagem , Citostáticos/efeitos adversos , Progressão da Doença , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Resistência a Medicamentos , Substituição de Medicamentos/métodos , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Monitorização Imunológica , Gravidade do Paciente , Indução de Remissão/métodos , Rituximab , Federação Russa/epidemiologia , Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Extravasation is a devastating complication of intravenous therapy that develops when a drug infiltrates the interstitial tissue surrounding the vein. Due to the uncertain and possibly dramatic outcome, early recognition and adequate treatment with the aid of a standardized protocol are needed. METHODS: A pubmed literature search was conducted and all relevant articles were reviewed for the development of an extravasation treatment protocol. RESULTS: An overview of current treatment guidelines and clinical experience is provided. The extravasation treatment protocol was implied during 1 year in this university hospital with satisfactory outcome. CONCLUSION: Treatment starts with prevention. In case of an established extravasation injury, early recognition, assessment of severity, and treatment with medical and/or surgical therapies are recommended.
Assuntos
Extravasamento de Materiais Terapêuticos e Diagnósticos/terapia , Animais , Fármacos Cardiovasculares/uso terapêutico , Protocolos Clínicos , Citostáticos/efeitos adversos , Citostáticos/uso terapêutico , Extravasamento de Materiais Terapêuticos e Diagnósticos/cirurgia , Humanos , Necrose , Razoxano/uso terapêutico , Pele/patologiaRESUMO
The function of liver and synthesized by it components of blood coagulation were studied on sampling of 25 patients with acute lymphoblastic leucosis in the debut of disease and under implementation of induction of remission. Before treatment the hepatotoxicity was detected in 40% of patients. The reliable correlation between level of aspartataminotransferase and number of leucocytes and blasts (rs = 0.401 and rs = 0.406 correspondingly) testifies the role of leucosis cells in functional disorders of liver during this period of disease. Against the background of cytostatic therapy the signs of liver damage were presented in 76% of patients. The maximum expressed hepatotoxicity was observed at 9-14 day of treatment. The decrease of components of hemostasis synthesized in liver was observed at 16-21 day of treatment. During this time the synthesis of factors of thrombin complex, antithrombin III and plasminogen was disordered. The plasminogen also decreased at the expense of its consumption as a result of fibrinolysis activation validated by decreased level of D-dimers. It is proved that in the debut and under treatment acute lymphoblastic leucosis the danger of development of thrombotic hemorrhagic complications is related both with derangement of synthesis of procoagulants, antithrombin III and plasminogen and with their consumption in case of activation of intravascular coagulation with leucosis process and cytostatic.
Assuntos
Hemostasia , Fígado/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Adolescente , Adulto , Idoso , Antitrombina III/metabolismo , Aspartato Aminotransferases/sangue , Citostáticos/efeitos adversos , Citostáticos/uso terapêutico , Feminino , Hemorragia/etiologia , Humanos , Quimioterapia de Indução , Leucócitos/patologia , Fígado/fisiopatologia , Hepatopatias/sangue , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Plasminogênio/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Trombina/metabolismoRESUMO
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.
Assuntos
Antineoplásicos , Citostáticos , Síndromes Neurotóxicas , Doenças do Sistema Nervoso Periférico , Humanos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Citostáticos/efeitos adversos , Estudos Prospectivos , Antineoplásicos/toxicidade , Imunoterapia/efeitos adversosRESUMO
Errors involving cytotoxic drugs have the potential of being fatal and should therefore be prevented. The objective of this article is to identify the characteristics of medication errors involving parenteral cytotoxic drugs in Sweden. A total of 60 cases reported to the national error reporting systems from 1996 to 2008 were reviewed. Classification was made to identify cytotoxic drugs involved, type of error, where the error occurred, error detection mechanism, and consequences for the patient. The most commonly involved cytotoxic drugs were fluorouracil, carboplatin, cytarabine and doxorubicin. The platinum-containing drugs often caused serious consequences for the patients. The most common error type were too high doses (45%) followed by wrong drug (30%). Twenty-five of the medication errors (42%) occurred when doctors were prescribing. All of the preparations were delivered to the patient causing temporary or life-threatening harm. Another 25 of the medication errors (42%) started with preparation at the pharmacies. The remaining 10 medication errors (16%) were due to errors during preparation by nurses (5/60) and administration by nurses to the wrong patient (5/60). It is of utmost importance to minimise the potential for errors in the prescribing stage. The identification of drugs and patients should also be improved.
Assuntos
Antineoplásicos , Citostáticos , Infusões Parenterais , Erros de Medicação/classificação , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Citostáticos/administração & dosagem , Citostáticos/efeitos adversos , Humanos , Infusões Parenterais/efeitos adversos , Erros de Medicação/estatística & dados numéricos , Papel do Profissional de Enfermagem , SuéciaRESUMO
Acute kidney injury is a common complication in hospitalized patients and is associated with substantially increased morbidity and mortality. Frequently, it is caused by impaired renal perfusion, ischemia and reperfusion injury, sepsis or urinary tract obstruction, but often its etiology is multifactorial. In this context, the contribution of nephrotoxic medications to the development of AKI plays an important role. This review begins with an attempt to evaluate the importance of drug-related acute kidney injury in general. Then, a selected list of 7 classes of drugs or compounds, namely aminoglycosides, aristolochic acid, cytostatic drugs, nonsteroidal anti-inflammatory drugs, osmotic agents, radiocontrast, and phosphate salts are discussed in depth, including their epidemiology, pathophysiology, clinical features and treatment. While not attempting to be exhaustive, this review attempts to provide an overview with additional in-depth information on certain classes of drugs that are either of general importance or have recently emerged in the literature.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Rim/efeitos dos fármacos , Aminoglicosídeos/efeitos adversos , Antibacterianos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Antivirais/efeitos adversos , Ácidos Aristolóquicos/efeitos adversos , Meios de Contraste/efeitos adversos , Citostáticos/efeitos adversos , Diuréticos Osmóticos/efeitos adversos , Humanos , Fosfatos/efeitos adversosRESUMO
In modern oncology chemotherapy (CT), along with the surgical technique and radiotherapy is a leader in the treatment of cancer patients. More than 60% of patients receiving chemotherapy at different stages of treatment. Recently, modern chemotherapy has become more urgent personal approach to the choice of drugs and their doses, aimed at reducing the toxicity of chemotherapy. Complications of chemotherapy significantly degrade the effectiveness of the treatment of patients with malignant tumors, because they require lower doses of anticancer drug, or lengthening the intervals between cycles of chemotherapy, which affects treatment outcomes and quality of life. This paper presents a literature review of toxic effects of cytostatic drugs on the gastrointestinal tract.
Assuntos
Antineoplásicos/efeitos adversos , Citostáticos/efeitos adversos , Trato Gastrointestinal/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Trato Gastrointestinal/patologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/patologia , Náusea/prevenção & controle , Neoplasias/patologia , Antagonistas da Serotonina/farmacologia , Antagonistas da Serotonina/uso terapêutico , Resultado do Tratamento , Vômito/prevenção & controleRESUMO
BACKGROUND: A characteristic cutaneous eruption related to the use of cytostatic chemotherapeutic drugs has been described in the literature. This condition appears to be characterized by an erythematous eruption, primarily affecting the intertriginous areas bilaterally, together with eccrine squamous syringometaplasia as the main histologic feature. OBJECTIVE: We sought to establish the epidemiologic, clinical, and histologic characteristics of this poorly defined chemotherapy drug-related eruption. METHODS: Retrospective data were collected from 21 consecutive patients with this clinical and histopathologic pattern who attended an oncology center between January 1999 and September 2009. Two skin biopsy specimens were obtained from all patients, with the first being taken within 24 hours of onset, and the second 72 to 96 hours after onset. RESULTS: The patients analyzed were predominantly female (72%), with a mean age of 52 years (range 10-69 years). The lesions presented clinically as bilateral erythematous plaques affecting both axillae (95%), groin (88%), and side aspects of the neck (48%). The main histologic feature in all cases was eccrine squamous syringometaplasia, characterized by the transformation of the eccrine cuboidal epithelium into two or more layers of squamous cells with intercellular bridges. The onset of the eruption appeared within 30 days (range 2-30 days) after the initiation of the cytostatic agent infusion. The lesions resolved with desquamation and postinflammatory hyperpigmentation. The same cutaneous pattern recurred in up to 50% of patients in whom the oncologist reintroduced the cytostatic treatment. LIMITATIONS: Small sample size was a limitation. CONCLUSIONS: We suggest the term "chemotherapy-related bilateral dermatitis associated with eccrine squamous syringometaplasia" to describe this distinctive entity, which is primarily associated with pegylated liposomal doxorubicin infusions and chemotherapeutic regimens used in autologous bone-marrow transplantation.
Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Citostáticos/efeitos adversos , Doxorrubicina/efeitos adversos , Toxidermias/etiologia , Adolescente , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Axila/patologia , Criança , Dermatite , Doxorrubicina/administração & dosagem , Toxidermias/epidemiologia , Toxidermias/patologia , Glândulas Écrinas/patologia , Feminino , Virilha/patologia , Humanos , Lipossomos , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Estudos Retrospectivos , Sirolimo/efeitos adversos , Sirolimo/análogos & derivados , Adulto JovemRESUMO
OBJECTIVE: To measure and provide an economic assessment of the preparations returned to a centralised cytostatic drug preparation unit, analyse reasons for their return, propose measures for minimising returns and assess their impact on the Medical Oncology division's outpatient services. METHODS: This prospective study contained two phases. During the first, we registered all returns, motives, cases of reuse and costs. In the second phase, we analysed returns at the Oncology outpatient division after having adopted measures to minimise the returns. RESULTS: During the first phase, 218 preparations (worth 51,131) were returned. The Oncology Day Hospital returned 1% of the preparations worth 1% of the total value; during the second phase, these figures were 0.56% of the preparations and 0.14% of the total value. CONCLUSIONS: Favouring reporting on and identifying expensive treatments with little stability and using returned preparations as a quality indicator for Oncology has improved management of the central cystostatic preparation unit.
Assuntos
Antineoplásicos , Serviços Centralizados no Hospital/organização & administração , Citostáticos , Serviço Hospitalar de Oncologia/estatística & dados numéricos , Serviço de Farmácia Hospitalar/organização & administração , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/economia , Serviços Centralizados no Hospital/economia , Citostáticos/administração & dosagem , Citostáticos/efeitos adversos , Citostáticos/economia , Combinação de Medicamentos , Composição de Medicamentos/economia , Custos de Medicamentos , Estabilidade de Medicamentos , Uso de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Hospitais Universitários/economia , Hospitais Universitários/organização & administração , Hospitais Universitários/estatística & dados numéricos , Humanos , Erros de Medicação , Neoplasias/tratamento farmacológico , Serviço Hospitalar de Oncologia/economia , Serviço de Farmácia Hospitalar/economia , Estudos Prospectivos , EspanhaRESUMO
The effect of cytostatic drug cyclophosphamide (CY) on lingual epithelium was studied in 90 female mice using histological, morphometric, quantitative histochemical and immunohistochemical methods. CY (400 mg/kg) was injected intraperitoneally three times with a 48 h interval. Material was obtained 2 days after injections and 10-20 days after their discontinuation. CY treatment was shown to result in the damage of both surface epithelium of the tongue and the epithelium of minor lingual salivary glands. Damage to the surface epithelium was more pronounced on the ventral surface of the tongue and was associated mainly with the disturbances of its proliferation. Changes were less severe on the dorsal surface and were seen as the disturbances of epithelial differentiation and desquamation. Glandular epithelium was damaged to a lesser extent than the surface one, with serocytes being more sensitive to the cytotoxic injury than mucocytes. After cytostatic drug discontinuation, the tendency for the normalization of the epithelial characteristics was noted. Most persistent changes in the surface epithelium were found on the dorsal surface of the tongue and in the glandular epithelium--in the serous secretory portions of the salivary glands.
Assuntos
Ciclofosfamida/efeitos adversos , Citostáticos/efeitos adversos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/patologia , Animais , Feminino , Camundongos , Glândulas Salivares Menores/efeitos dos fármacos , Glândulas Salivares Menores/patologia , Língua/efeitos dos fármacos , Língua/patologiaRESUMO
In the preceding work ("Morphology", 2011, issue 2), the regularities of oral mucosal (OM) epithelium injury after the cytostatic drug (CSD) treatment and its further regeneration, were reviewed. This paper presents the systematized summary of current literature data and the authors' own findings on the regularities of CSD effect on non-epithelial OM cell populations and their interactions with each other and the epithelium. The changes of intraepithelial tissue homeostasis, associated with CSD effect on intraepithelial lymphocytes, granulocytes, dendritic antigen presenting cells and melanocytes, interacting with epitheliocytes, are described. The data are presented, indicating that along with the epithelium, the cell populations of lamina propria and submucosal connective tissue, as well as the small blood vessels, are important targets of CSD in the OM tissues. The concept of a unifying model, describing tissue, cellular and molecular mechanisms of the oral mucositis development after CSD treatment, is reviewed.
Assuntos
Comunicação Celular/efeitos dos fármacos , Citostáticos/efeitos adversos , Mucosa Bucal , Animais , Homeostase/efeitos dos fármacos , Humanos , Mucosa Bucal/irrigação sanguínea , Mucosa Bucal/citologia , Mucosa Bucal/efeitos dos fármacos , Estomatite/induzido quimicamenteRESUMO
This paper presents the systematized summary of current literature data and the authors' own findings on the regularities of human and animal surface oral mucosal epithelium (OME) injury caused by cytostatic drugs (CSD) administration, and on the ways of its regeneration after the cytostatic chemotherapy (CSCT) discontinuation. Tissue, cell and molecular mechanisms of CSCT effects on OME, are described. The direct effects of CSD included the epithelial layer attenuation with the derangement of its architecture, epitheliocyte proliferation suppression, apoptosis activation, and differentiation disturbances (involving the broad spectrum of cytological, cytochemical, ultrastructural and molecular-biological changes). In severe cases, these processes resulted in the loss of the epithelial layer integrity with the development of ulceration. Complete epithelial regeneration requires a long period after the CSCT discontinuation. Indirect effects of CSD on OME are associated with the microbial invasion and the diffusion of microbial vital activity products into the epithelium with concurrent leukopenia, immunosuppression and decreased salivary secretion.
Assuntos
Citostáticos/efeitos adversos , Mucosa Bucal , Regeneração/fisiologia , Estomatite , Apoptose/efeitos dos fármacos , Candidíase/etiologia , Diferenciação Celular/efeitos dos fármacos , Citocinas/efeitos adversos , Células Epiteliais/patologia , Células Epiteliais/fisiologia , Epitélio/patologia , Epitélio/fisiologia , Infecções por Bactérias Gram-Negativas/etiologia , Infecções por Bactérias Gram-Positivas/etiologia , Humanos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/patologia , Mucosa Bucal/fisiologia , Espécies Reativas de Oxigênio/efeitos adversos , Estomatite/etiologia , Estomatite/fisiopatologiaRESUMO
Paravasation of cytostatic drugs during peripheral intravenous administration is a well known complication. In the United States of America it occurs in seven percent of cases with different severity and consequences. Although methods to completely avoid this complication are still unavailable, we are able to decrease the risks by identifying the patient- and procedure-related factors. The educated patient is a good indicator of paravasation in case he or she can cooperate and call the nurse. When the patient is unable to cooperate, the risks of extravasation is higher and closer nursing surveillance is indicated. The extent of injury depends mainly on the chemical structure of the extravasant substance (vesicant, irritant or non-vesicant) which may be modified by other factors. There is no strong evidence-based guidance for the management of complication. Abrupt cessation of the infusion and drawing back on the inserted venous catheter as well as elevating and resting the affected limb are necessary measures. In the available literature cooling or warming of the affected area is controversial. Similarly there are still open questions regarding the value of using antidotes as dexrazoxane, dimethylsulfoxide, thiosulfate and hyaluronidase (which is not registered as medicament in Hungary). In the event of extravasation early multidisciplinary dermatological and surgical assessment is essential for definitive diagnosis and setting the optimal management.
Assuntos
Antídotos/uso terapêutico , Antineoplásicos/efeitos adversos , Citostáticos/efeitos adversos , Extravasamento de Materiais Terapêuticos e Diagnósticos/diagnóstico , Extravasamento de Materiais Terapêuticos e Diagnósticos/terapia , Pele/efeitos dos fármacos , Antineoplásicos/administração & dosagem , Cateteres de Demora , Crioterapia , Citostáticos/administração & dosagem , Dimetil Sulfóxido/uso terapêutico , Extravasamento de Materiais Terapêuticos e Diagnósticos/epidemiologia , Humanos , Hungria/epidemiologia , Hialuronoglucosaminidase/uso terapêutico , Infusões Intravenosas , Comunicação Interdisciplinar , Irritantes/efeitos adversos , Razoxano/uso terapêutico , Fatores de Risco , Tiossulfatos/uso terapêutico , Estados Unidos/epidemiologiaRESUMO
Extravasation of cytostatics occurs when an infusion containing a cytotoxic drug leaks into the surrounding perivascular and subcutaneous tissues. Incidence of cytostatic extravasation is found to be 0.1-6% according to the literature. Depending on the severity of complications, pain, loss of function in the extremities, or in extreme cases tissue necrosis necessitating an amputation may develop, drawing consequences like delay or interruption of the chemotherapy. Extent of complications is greatly influenced by the type of medication administered, general condition of the patient, and professional preparedness of staff providing the oncological health service. The protocol recently implemented in the National Institute of Oncology is a short, compact guidance for physicians and nurses providing oncological care, so by quick and adequate management of extravasation cases, severe complications could be prevented. More complex practical guidelines including algorithms could be created as a result of a wider collaboration, with the help of which oncological health professionals could easily cope with this rare problem. The authors describe in their review the implementation of the use of dry warm and cold packs, dymethylsulfoxide and hyaluronidase and their function within the algorithm of extravasation treatment.