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1.
Zhonghua Zhong Liu Za Zhi ; 42(3): 170-179, 2020 Mar 23.
Artigo em Chinês | MEDLINE | ID: mdl-32252195

RESUMO

Taxanes are cornerstones of cancer chemotherapy and can be used for the treatment of various tumors, including breast cancer. Taxane-associated peripheral neuropathy is a common adverse effect of taxanes, leading to discontinuation of drug therapy, affecting drug treatment outcomes, and severely affecting patients' quality of life. This consensus addresses and recommends the pathogenesis, clinical features, associated risk factors, diagnostic evaluation, prevention, and treatment of taxane-related peripheral neuropathy. It is hoped that this consensus will standardize the current management of taxane-related peripheral neuropathy in China and improve clinicians' understanding of taxane-related peripheral neuropathy, thereby improving patient outcomes and improving patient quality of life.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Síndromes Neurotóxicas/diagnóstico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Hidrocarbonetos Aromáticos com Pontes , China , Consenso , Humanos , Síndromes Neurotóxicas/etiologia , Guias de Prática Clínica como Assunto , Qualidade de Vida
2.
Medicine (Baltimore) ; 99(11): e19566, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176115

RESUMO

Chemotherapy may cause ovarian toxicity and infertility. Cancer patients are usually overwhelmed, and focus exclusively on cancer diagnosis and may not pay attention to fertility-related issues. In this paper we look at the rate of amenorrhea and fertility counseling among such young patients.Premenopausal women with early-stage breast cancer treated with adjuvant or neoadjuvant chemotherapy were recruited. Amenorrhea was defined as absence of menstruation for ≥12 months after the completion of chemotherapy.A total of 94 patients met the eligibility criteria and were included in this analysis. Median age at diagnosis was 35.7 (range, 22-44) years. Seventy-nine (85.9%) respondents were counseled about amenorrhea and 37 (40.2%) were considering having children. Long-term amenorrhea was reported by 51 (54.3%) patients. The addition of taxanes to anthracyclines, in 2 different regimens, increased the risk of amenorrhea to 69.2% and 66.7% compared to 38.9% with anthracycline-alone, P < .0001. Longer duration of chemotherapy (≥24 weeks) might also be associated with higher rate of amenorrhea (67.7%) compared to 43.4% in those who had shorter duration (<24 weeks), P = .031.The addition of taxanes to anthracycline-based chemotherapy increased the risk of amenorrhea. However, shorter duration of chemotherapy, even with taxanes, may lower such risk. Our study highlights the importance of fertility counseling to improve fertility preservation rates. Given the importance of taxanes, shorter regimens are associated with lower amenorrhea rates and should be preferred over longer ones.


Assuntos
Amenorreia/induzido quimicamente , Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Preservação da Fertilidade , Taxoides/efeitos adversos , Adulto , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/efeitos adversos , Aconselhamento , Feminino , Humanos , Jordânia , Estadiamento de Neoplasias , Estudos Retrospectivos , Adulto Jovem
3.
J Cancer Res Clin Oncol ; 146(2): 449-455, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838576

RESUMO

PURPOSE: Outcomes of multiply relapsed, refractory germ-cell tumour (GCT) patients remain poor with an overall survival (OS) of a few months only. Thus, new therapeutic advances are urgently needed. Cabazitaxel has shown preclinical activity in platinum-resistant GCT models. Here, we report the first clinical case series of cabazitaxel treatment for platinum-refractory GCT. METHODS: Data of multiply relapsed GCT patients receiving single-agent cabazitaxel were retrospectively analysed. Endpoints included 12-week progression-free survival (PFS) rate, disease control rate, tumour marker responses, median PFS and OS, and toxicity. RESULTS: Cabazitaxel showed limited activity in 13 heavily pre-treated GCT patients. After a median follow-up of 23 weeks (IQR 29), 69% of patients were deceased. A median of 2 cycles of cabazitaxel (range 1-7) were applied. The 12-week PFS rate was 31%. Median PFS and OS were 7 and 23 weeks, respectively. Two patients achieved objective responses (15%), three patients (23%) achieved a tumour marker decline ≥ 50%, and the disease control rate was 39%. Cabazitaxel was well tolerated. CTCAE° III-IV haemato-toxicity was most common (54%), and dose reductions were scarce (15%). CONCLUSION: In this case series, cabazitaxel showed limited activity in heavily pre-treated GCT patients. Two-phase II studies are underway (NCT02115165, NCT02478502) prospectively assessing cabazitaxel in multiply relapsed GCTs.


Assuntos
Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Taxoides/uso terapêutico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/patologia , Metástase Neoplásica , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/patologia , Estudos Retrospectivos , Taxoides/efeitos adversos , Neoplasias Testiculares/patologia
4.
Int J Cancer ; 146(2): 321-328, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30839100

RESUMO

The absolute risk reduction by prophylaxis in chemotherapy-induced febrile neutropenia (FN) is largest in patients at highest underlying risk. Therefore, reliable predictive models are needed. Here, we develop and validate such a model for risk of FN during chemotherapy cycles 2-6. A prediction score for risk of FN during the first cycle has recently been published. Patients with solid cancers initiating first-line chemotherapy in 2010-2016 were included. Cycle-specific risk factors were assessed by Poisson regression using generalized estimating equations and random split sampling. The derivation cohort included 4,590 patients treated with 15,419 cycles, wherein 326 (2.1%) FN events occurred. Predictors of FN in multivariable analyses were: higher predicted risk of FN in the first cycle, platinum- or taxane-containing therapies, concurrent radiotherapy, treatment in cycle 2 compared to later cycles, previous FN or neutropenia and not receiving granulocyte colony-stimulating factors. Each predictor added between -2 and 8 points to each patient's score (median score 4; interquartile range, 1-6). The incidence rate ratios for developing FN in the intermediate (score 1-4), high (score 5-6) and very high risk groups (score ≥7) were 7.8 (95% CI, 2.4-24.9), 18.6 (95% CI, 5.9-58.8) and 51.7 (95% CI, 16.5-162.3) compared to the low risk group (score ≤0), respectively. The score had good discriminatory ability with a Harrell's C-statistic of 0.78 (95% CI, 0.76-0.80) in the derivation and 0.75 (95% CI, 0.72-0.78) in the validation cohort (patient n = 2,295, cycle n = 7,670). The Cycle-Specific Risk of FEbrile Neutropenia after ChEmotherapy score is the first published method to estimate cycle-specific risk of FN.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Modelos Biológicos , Neoplasias/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia/etiologia , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Dinamarca/epidemiologia , Esquema de Medicação , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Compostos de Platina/administração & dosagem , Compostos de Platina/efeitos adversos , Distribuição de Poisson , Medição de Risco/métodos , Fatores de Risco , Taxoides/administração & dosagem , Taxoides/efeitos adversos
5.
Medicine (Baltimore) ; 98(51): e18436, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861013

RESUMO

RATIONALE: Latent tuberculosis infection (LTBI) describes the dormant state of tuberculosis (TB), in which persistent immune-related interaction between TB and T-cells maintain its state. Cabazitaxel (CBZ) is reported to improve overall survival in patients with castration-resistant prostate cancer (CRPC) after progression observed in regimens including docetaxel. CBZ is known for severe myelosuppression; however there is no recommendation for the treatment of LTBI before CBZ treatment. To the authors' knowledge, this is the first report to describe reactivation of LTBI induced by CBZ. PATIENT CONCERNS: A 75-year-old Japanese male with a medical history of TB since 16 years of age had been treated for prostate cancer (PC) (initial prostate-specific antigen 532 ng/ml; cT4N1M1b; Gleason score4+4) with androgen deprivation therapy, abiraterone, and docetaxel. Calcified nodules and radiological findings of LTBI were present in the upper right lobe since the diagnosis of PC. After progression was observed during these treatments, CBZ was administered combined with pegfilgrastim, long-acting granulocyte colony-stimulating factor (G-CSF). Seven days after the third course of CBZ, he was admitted to the authors' hospital to treat febrile neutropenia (FN). High fever persisted even after myelosuppression had recovered. Computed tomography (CT) revealed distribution of small nodules in the bilateral lungs, for which miliary TB was included in the differential diagnosis. T-Spot, interferon-gamma-release assay, and bronchoscopy yielded no significant findings; however, sputum and urine culture confirmed the diagnosis of TB. DIAGNOSIS: CT, sputum and urine culture confirmed the diagnosis of miliary TB. INTERVENTIONS: The patient was treated with anti-bacterial therapy (cefepime) on hospital admission, which was not effective. After the diagnosis of miliary TB was confirmed, anti-TB drugs, including isoniazid, rifampicin, pyrazinamide and ethambutol, were administered. OUTCOMES: Despite anti-TB therapy, high fever persisted and radiological findings worsened. Fifty days after the third course of CBZ, the patient died of respiratory dysfunction caused by progression of miliary TB. LESSONS: Management of LTBI is needed in cases of radiographic findings of LTBI and medical history of TB before CBZ treatment, despite the rarity of LTBI reactivation in patients with PC.


Assuntos
Tuberculose Latente , Neoplasias da Próstata/tratamento farmacológico , Taxoides/efeitos adversos , Tuberculose Miliar/induzido quimicamente , Idoso , Antituberculosos/uso terapêutico , Evolução Fatal , Humanos , Masculino , Neoplasias da Próstata/complicações , Tuberculose Miliar/tratamento farmacológico
6.
Nihon Yakurigaku Zasshi ; 154(5): 241-244, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31735751

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect frequently caused by taxanes. Because the mechanisms underlying CIPN pathogenesis remain to be fully elucidated, there is no indicator for objective diagnosis like a biomarker. In addition, treatment options for CIPN is still unsatisfactory. We have previously demonstrated that paclitaxel preferentially impair myelin-forming Schwann cells, and consequently induce dedifferentiation and demyelination of Schwann cells. Recently, in a paclitaxel CIPN model mouse, we found that an inflammatory factor is released from dedifferentiated Schwann cells in the mouse sciatic nerve into the blood, highly correlated with the on-set of mechanical hypersensitivity. On the other hand, considering our previous findings, it seems that some drugs, which supply newly formed mature Schwann cells at the sites of demyelinated lesions, may be a new beneficial therapy for taxane-induced peripheral neuropathy. In this review, we will introduce our findings about new therapeutic drug candidate for taxane-related CIPN based on this concept, and plasma biomarker to detect CIPN on-set and progression.


Assuntos
Antineoplásicos/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/terapia , Taxoides/efeitos adversos , Animais , Biomarcadores , Camundongos , Células de Schwann/efeitos dos fármacos
7.
N Engl J Med ; 381(26): 2506-2518, 2019 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-31566937

RESUMO

BACKGROUND: The efficacy and safety of cabazitaxel, as compared with an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who were previously treated with docetaxel and had progression within 12 months while receiving the alternative inhibitor (abiraterone or enzalutamide) are unclear. METHODS: We randomly assigned, in a 1:1 ratio, patients who had previously received docetaxel and an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide) to receive cabazitaxel (at a dose of 25 mg per square meter of body-surface area intravenously every 3 weeks, plus prednisone daily and granulocyte colony-stimulating factor) or the other androgen-signaling-targeted inhibitor (either 1000 mg of abiraterone plus prednisone daily or 160 mg of enzalutamide daily). The primary end point was imaging-based progression-free survival. Secondary end points of survival, response, and safety were assessed. RESULTS: A total of 255 patients underwent randomization. After a median follow-up of 9.2 months, imaging-based progression or death was reported in 95 of 129 patients (73.6%) in the cabazitaxel group, as compared with 101 of 126 patients (80.2%) in the group that received an androgen-signaling-targeted inhibitor (hazard ratio, 0.54; 95% confidence interval [CI], 0.40 to 0.73; P<0.001). The median imaging-based progression-free survival was 8.0 months with cabazitaxel and 3.7 months with the androgen-signaling-targeted inhibitor. The median overall survival was 13.6 months with cabazitaxel and 11.0 months with the androgen-signaling-targeted inhibitor (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.89; P = 0.008). The median progression-free survival was 4.4 months with cabazitaxel and 2.7 months with an androgen-signaling-targeted inhibitor (hazard ratio for progression or death, 0.52; 95% CI, 0.40 to 0.68; P<0.001), a prostate-specific antigen response occurred in 35.7% and 13.5% of the patients, respectively (P<0.001), and tumor response was noted in 36.5% and 11.5% (P = 0.004). Adverse events of grade 3 or higher occurred in 56.3% of patients receiving cabazitaxel and in 52.4% of those receiving an androgen-signaling-targeted inhibitor. No new safety signals were observed. CONCLUSIONS: Cabazitaxel significantly improved a number of clinical outcomes, as compared with the androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who had been previously treated with docetaxel and the alternative androgen-signaling-targeted agent (abiraterone or enzalutamide). (Funded by Sanofi; CARD ClinicalTrials.gov number, NCT02485691.).


Assuntos
Antagonistas de Androgênios/administração & dosagem , Androstenos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Androstenos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Feniltioidantoína/administração & dosagem , Feniltioidantoína/efeitos adversos , Prednisona/administração & dosagem , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/mortalidade , Taxoides/efeitos adversos
8.
Anticancer Res ; 39(8): 4411-4414, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366538

RESUMO

BACKGROUND/AIM: Cabazitaxel use has usually been limited to up to 10 cycles in most countries according to the protocol in the TROPIC trial. Therefore, clinical data on cabazitaxel use beyond 10 cycles is limited. The aim of this study was to report the therapeutic outcome of cabazitaxel chemotherapy administered for >10 cycles. PATIENTS AND METHODS: This study included 74 Japanese patients with prostate cancer between 2014 and 2017. Patients background, and treatment outcomes including PSA decline, progression-free survival, treatment-failure-free survival, overall survival, and adverse events were investigated, comparing patients treated with ≤10 and >10 cycles. RESULTS: Patients characteristics were favorable as indicated by the higher number of cycles of prior docetaxel chemotherapy, absence of pain, and absence of bony and visceral metastases among men who received >10 cycles of cabazitaxel. PSA response, progression-free survival, treatment-failure-free survival and overall survival were better among patients treated with >10 cycles of cabazitaxel compared to those treated with ≤10 cycles. The incidence of severe adverse events was similar between the two groups. CONCLUSION: Taken together, this study suggested that continuous chemotherapy with cabazitaxel beyond 10 cycles may be beneficial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel/efeitos adversos , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/efeitos adversos , Resultado do Tratamento
9.
BMC Cancer ; 19(1): 766, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382926

RESUMO

BACKGROUND: To describe the patterns of second-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel treatment in a Spanish population, to identify the factors associated with those patterns, and to compare the efficacy and safety of the treatments most frequently administered. METHODS: Observational, prospective study conducted in patients with histologically or cytologically confirmed prostate adenocarcinoma; documented metastatic castration-resistant disease; progression after first-line, docetaxel-based chemotherapy with or without other agents. RESULTS: Of the 150 patients recruited into the study, 100 patients were prescribed abiraterone acetate plus prednisone (AAP), 44 patients received cabazitaxel plus prednisone (CP), and 6 patients received other treatments. Age (odds ratio [OR] 1.06, 95% [confidence interval] CI 1.01 to 1.11) and not elevated lactate dehydrogenase (LDH) levels (OR 0.33, 95% CI 0.14 to 0.76) were independently associated with the administration of AAP. Treatment with AAP was associated with significantly longer clinical/radiographic progression-free survival (hazard ratio [HR] 0.57, 95% CI 0.38 to 0.85) and overall survival (OS; HR 0.40, 95% CI 0.21 to 0.76) compared to CP, while no significant differences between the treatments were found regarding biochemical progression-free survival (PFS; HR 0.78 [95% CI 0.49 to 1.24]). However, in a post-hoc Cox regression analysis adjusted for potential confounders there were not differences between AAP and CP in any of the time-to-event outcomes, including overall survival. We observed no new safety signals related to either regimen. CONCLUSION: Second-line AAP for patients with mCRPC is the most common treatment strategy after progression with a docetaxel-based regimen. When controlling for potential confounders, patients receiving this treatment showed no differences in PFS and OS in comparison to those receiving CP, although these latter results should be confirmed in randomized controlled trials.


Assuntos
Acetato de Abiraterona/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Docetaxel/uso terapêutico , Prednisona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Acetato de Abiraterona/efeitos adversos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia/etiologia , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Astenia/etiologia , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/análise , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Dor/etiologia , Prednisona/efeitos adversos , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Espanha , Taxoides/efeitos adversos , Resultado do Tratamento
10.
Support Care Cancer ; 27(10): 3729-3737, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31363906

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual's specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field.


Assuntos
Antineoplásicos/efeitos adversos , Síndromes Neurotóxicas/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Bortezomib/efeitos adversos , Predisposição Genética para Doença/genética , Humanos , Taxoides/efeitos adversos , Alcaloides de Vinca/efeitos adversos
11.
Medicine (Baltimore) ; 98(30): e16563, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348280

RESUMO

BACKGROUND: Many studies were performed to explore the correlation between taxane-based chemotherapy and the risk of breast cancer-related lymphedema (BCRL), however, with inconsistent results. Hence, the purpose of this study is to evaluate whether taxane-based chemotherapy is a risk factor for BCRL. METHODS: A comprehensive systematic search of clinical trials published in the PubMed, Embase and the Cochrane Library databases will be conducted to identify eligible studies up to the date of December 31, 2018. We will employ risk ratios with 95% confidence intervals (95% CIs) to estimate the correlations between taxane-based chemotherapy and BCRL. Meta-analysis will be performed using Stata SE version 12.0 software. RESULTS: The results of this systematic review and meta-analysis will provide a high-quality synthesis of existing evidence of the correlations between taxane-based chemotherapy and the risk of BCRL. CONCLUSION: The protocol will provide updated evidence for the use of taxane-based chemotherapy in postoperative breast cancer patients. ETHICS AND DISSEMINATION: It is not necessary for ethical approval because it is based on published studies. The protocol will be disseminated in a peer-reviewed journal or presented at a topic-related conference. TRIAL REGISTRATION: This systematic review protocol has been registered with a number of CRD42019123989.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Linfedema/induzido quimicamente , Taxoides/efeitos adversos , Feminino , Humanos , Metanálise como Assunto , Projetos de Pesquisa , Fatores de Risco , Revisões Sistemáticas como Assunto
12.
BMC Cancer ; 19(1): 720, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331293

RESUMO

BACKGROUND: Interstitial pneumonitis is a rare reaction in a previously irradiated area of pulmonary or thoracic lesion after treatment with anticancer drugs such as taxanes. CASE PRESENTATION: A 66-year-old man presented with a fever and dyspnea after treatment with cabazitaxel for castration-resistant prostate cancer. He was treated with an intravenous broad-spectrum antimicrobial agent, however he complained of dyspnea and had a pulse oximetric saturation of 80% while breathing room air. The patients had been treated for bone metastases with 37.5 Gy to the thoracic spine (Th 7) as a local radiotherapy. Radiological images showed pulmonary interstitial opacities in the irradiated field of the both lungs. The steroid pulse therapy was started. The patient's dyspnea disappeared and the interstitial opacities had also improved. CONCLUSIONS: This report is a case of interstitial pneumonitis in a castration-resistant prostate cancer patient receiving cabazitaxel after thoracic radiation therapy.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Doenças Pulmonares Intersticiais/induzido quimicamente , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Administração Intravenosa , Idoso , Antineoplásicos/administração & dosagem , Docetaxel/efeitos adversos , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Dispneia/tratamento farmacológico , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Taxoides/administração & dosagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Breast Cancer ; 26(6): 826-834, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31254201

RESUMO

BACKGROUND: Information on deaths occurring during oncological clinical trials has never been systematically assessed. Here, we examine the incidence of death and the profile of patients who died during randomized clinical breast cancer (BC) trials. METHODS: Information on fatal events during German Breast Group (GBG) led BC trials was prospectively captured. Data were derived from the trial databases and death narratives. All deaths were evaluated for possible causes, underlying conditions, treatment relatedness, time point and rate of autopsies. RESULTS: From 12/1996 to 01/2017, 23,387 patients were treated within 32 trials. Of those 88 (0.4%) died on therapy within 17 trials. Median age was 64 [range 35-84] years, 63.2% of patients had a body mass index (BMI) ≥ 25 kg/m2; 65.9% 1-3 and 22.7% ≥ 4 comorbidities; 61.4% 1-2 cardiovascular risk factors (CRFs); 26.4% took > 3 drugs; 81.7% had ECOG 0; 50.0% stage III, 76.7% luminal BC. The main causes of death were infection (38.6%; of those, 82.3% sepsis, 17.6% pneumonia), heart failure (14.8%), and pulmonary embolism (13.6%). Fatal events mainly occurred within the first 4 therapy cycles (55.7%), in the investigational arm (66.7%) and under anthracycline-taxane-based chemotherapy (51.1%). A relationship with the treatment was declared in 27.3% of the cases. An autopsy was performed in 13.6% of patients. CONCLUSIONS: Death during study treatment was mainly related to infections, and patients with advanced disease, high BMI, underlying comorbidities, CRFs and concomitant medications. If considered for study participation these patients need careful monitoring due to their higher risk for death on study.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/efeitos adversos , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Autopsia , Índice de Massa Corporal , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Comorbidade , Feminino , Alemanha , Insuficiência Cardíaca/complicações , Humanos , Pessoa de Meia-Idade , Segurança do Paciente , Pneumonia/complicações , Estudos Prospectivos , Embolia Pulmonar/complicações , Fatores de Risco , Sepse/complicações , Taxoides/efeitos adversos , Taxoides/uso terapêutico
14.
Eur J Cancer Care (Engl) ; 28(5): e13118, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31184794

RESUMO

OBJECTIVE: This meta-analysis was performed to assess the efficacy of cryotherapy and nail solution (NS) use in preventing nail toxicity (NT) induced by taxane-based chemotherapy. METHODS: PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov registry databases were searched for relevant studies published up to December 2018. The primary outcome was taxane-induced NT. Secondary outcomes were skin toxicity (ST), time to toxicity and patient comfort. RESULTS: We reviewed three randomised control trials and six prospective studies with 708 patients. For meta-analysis, taxane-induced NT grading was compared. NT and ST were significantly lower in the cryotherapy patients than in the controls (grade 1 NT: risk ratio [RR] = 0.51, 95% confidence interval [CI] = 0.30-0.89; grade 2-3 NT: RR = 0.36, 95% CI = 0.11-1.12; total NT: RR = 0.49; 95% CI = 0.30-0.79; ST: RR = 0.46, 95% CI = 0.33-0.64). The NS-treated patients exhibited significantly lower NT than the controls. CONCLUSIONS: Nail solution-treated or cryotherapy patients exhibited lower NT incidence and severity associated with taxane-based chemotherapy than the controls. For patients who can afford and comply with NS use or cryotherapy, these measures represent effective prophylactic management for taxane-induced NT and improve their quality of life and functional statuses. Further studies are needed to establish the routine usage protocols, long-term efficacy and safety for these interventions.


Assuntos
Crioterapia/métodos , Doenças da Unha/prevenção & controle , Neoplasias/tratamento farmacológico , Óleos Voláteis/uso terapêutico , Óleos Vegetais/uso terapêutico , Taxoides/efeitos adversos , Ceras/uso terapêutico , Docetaxel/efeitos adversos , Humanos , Doenças da Unha/induzido quimicamente , Onicólise/induzido quimicamente , Onicólise/prevenção & controle , Paclitaxel/administração & dosagem , Paroniquia/induzido quimicamente , Paroniquia/prevenção & controle , Transtornos da Pigmentação/induzido quimicamente , Transtornos da Pigmentação/prevenção & controle
15.
Anticancer Res ; 39(6): 3089-3094, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177153

RESUMO

BACKGROUND/AIM: Limited information is available to help physicians decide when to introduce cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC) patients. The objective of this study was to assess the optimal timing of cabazitaxel introduction. PATIENTS AND METHODS: The clinical outcomes of 66 mCRPC patients receiving cabazitaxel following failure of docetaxel were retrospectively analyzed. RESULTS: Among the parameters possibly affecting the timing of cabazitaxel introduction, only an increased prostate-specific antigen (PSA) value from the diagnosis of CRPC had a significant impact on overall survival (OS) after the introduction of cabazitaxel. Furthermore, there was a significant correlation between the increased PSA value from the diagnosis of CRPC and the baseline PSA value at cabazitaxel introduction. Multivariate analysis showed that only the baseline PSA value at cabazitaxel introduction is an independent predictor of OS. CONCLUSION: A comparatively low PSA value could be an alternative index suggesting the optimal timing for cabazitaxel introduction.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Esquema de Medicação , Humanos , Japão , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Taxoides/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
16.
BMC Cancer ; 19(1): 625, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238987

RESUMO

BACKGROUND: Chemotherapy may be a valuable treatment option as neoadjuvant treatment for locally advanced penile cancer according to some previous studies, but the rarity of the sample and the Lack of large-scale clinical trials hampered the attempt to establish a solid evidence base for its routine use. The purpose of this study was to evaluate the efficacy of the neoadjuvant chemotherapy combined with a ITP regimen including docetaxel, cisplatin and ifosfamide for treating advanced penile cancer patients. METHODS: A total of 19 patients who were classified into advanced penile cancer (PN3) received neoadjuvant chemotherapy of ITP regimen from June 2009 to June 2016 in our hospital. RESULTS: After chemotherapy 12 patients had a partial response (PR), 5 had stable disease (SD) and progressive disease (PD) in 2 cases. The 12 responders underwent penectomy, bilateral inguinal lymphadenectomy (ILND) and pelvic lymph node dissection (LPLND). In contrast, 7 cases who were non-responsive received palliative local radiotherapy. After a median follow-up of 30.6 months, there was statistically significant improvement in median PFS and OS among patients who experienced an objective response to neoadjuvant chemotherapy (group A) compared with those patients who did not respond to chemotherapy (group B) (log-rank test; P < 0.001). CONCLUSION: Neoadjuvant docetaxel, cisplatin and ifosfamide chemotherapy gave 63% (12/19) of patients who were diagnosed with stage n3 penile cancer the chance of radical resection of metastases, and their OS and PFS were significantly higher than those who could not be operated on and the therapeutic dose, toxic and side effects are acceptable in the Chinese Han population. Therefore, neoadjuvant ITP chemotherapy in the treatment of stage T3 penile cancer patients may have cheerful prospects in the Chinese Han population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Metástase Linfática/patologia , Neoplasias Penianas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Progressão da Doença , Docetaxel/administração & dosagem , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Canal Inguinal , Estimativa de Kaplan-Meier , Excisão de Linfonodo/métodos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Penianas/mortalidade , Neoplasias Penianas/patologia , Pênis/cirurgia , Taxoides/administração & dosagem , Taxoides/efeitos adversos
17.
Drugs ; 79(9): 969-995, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31127530

RESUMO

Increases in cancer diagnosis have tremendous negative impacts on patients and their families, and major societal and economic costs. The beneficial effect of chemotherapeutic agents on tumor suppression comes with major unwanted side effects such as weight and hair loss, nausea and vomiting, and neuropathic pain. Chemotherapy-induced peripheral neuropathy (CIPN), which can include both painful and non-painful symptoms, can persist 6 months or longer after the patient's last chemotherapeutic treatment. These peripheral sensory and motor deficits are poorly treated by our current analgesics with limited effectiveness. Therefore, the development of novel treatment strategies is an important preclinical research focus and an urgent need for patients. Approaches to prevent CIPN have yielded disappointing results since these compounds may interfere with the anti-tumor properties of chemotherapeutic agents. Nevertheless, the first (serotonin noradrenaline reuptake inhibitors [SNRIs], anticonvulsants, tricyclic antidepressants) and second (5% lidocaine patches, 8% capsaicin patches and weak opioids such as tramadol) lines of treatment for CIPN have shown some efficacy. The clinical challenge of CIPN management in cancer patients and the need to target novel therapies with long-term efficacy in alleviating CIPN are an ongoing focus of research. The endogenous cannabinoid system has shown great promise and efficacy in alleviating CIPN in preclinical and clinical studies. In this review, we will discuss the mechanisms through which the platinum, taxane, and vinca alkaloid classes of chemotherapeutics may produce CIPN and the potential therapeutic effect of drugs targeting the endocannabinoid system in preclinical and clinical studies, in addition to cannabinoid compounds diffuse mechanisms of action in alleviation of CIPN.


Assuntos
Antineoplásicos/efeitos adversos , Canabinoides/uso terapêutico , Dor Crônica/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neuralgia/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Canabinoides/farmacologia , Dor Crônica/induzido quimicamente , Ensaios Clínicos como Assunto , Humanos , Neuralgia/induzido quimicamente , Compostos Organoplatínicos/efeitos adversos , Taxoides/efeitos adversos , Resultado do Tratamento , Alcaloides de Vinca/efeitos adversos
18.
J BUON ; 24(2): 516-521, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31127999

RESUMO

PURPOSE: This article focuses on how the status of hormone receptors (HR) influences the efficacy of trastuzumab in patients with metastatic HER2-positive breast cancer treated with first-line trastuzumab in combination with taxane-based chemotherapy. METHODS: A prospective study was carried out at the Clinic for Oncology, Clinical Centre in Nis, from January 2015 to until June 2018. A total of 121 patients were treated with first-line trastuzumab in combination with taxane-based chemotherapy. None of the patients from the HR-positive group received hormonotherapy after completion of chemotherapy with trastuzumab. RESULTS: Clinical benefit rate was present in 76% of the patients, including partial response (PR) in 37%, stable disease (SD) in 38%, and complete response (CR) in almost 8% of the patients. Progressive disease (PD) occurred in almost a quarter of the patients, i.e. 24%. Progression-free survival (PFS) in the entire group of patients amounted to 9 months, whereas overall survival (OS) was 30 months. PFS in the HR-negative tumor group was significantly longer (13 months) compared to 8 months in the HR-positive tumor group (p<0.0001; HR 0.49;95% CI 0.31-0.69). Furthermore, OS was significantly longer in the HR-negative tumor group (34 months), compared to 26 months in the HR-positive tumor group (p=0.0073, HR 0.57; 95% CI 0.36-0.90). CONCLUSIONS: These data indicate a different response to anti-HER2 therapy in patients with HER2+ metastatic breast cancer (MBC) according to HR status, thus emphasizing that ER most likely represents an escape pathway for the response to anti-HER2 target therapy and vice versa. Combining hormonotherapy with anti-HER2 therapy surely represents a promising strategy which could help overcome resistance to trastuzumab and other anti-HER2 agents.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Trastuzumab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Estudos Prospectivos , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Trastuzumab/efeitos adversos , Resultado do Tratamento
19.
J BUON ; 24(2): 522-528, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31128000

RESUMO

PURPOSE: To observe the efficacy of neoadjuvant chemotherapy (NAC) in patients with breast cancer (BC) and to investigate the effect of Annexin A3 (ANXA3) expression. METHODS: 158 patients with BC treated in Yantai Yuhuangding Hospital from September 2015 to December 2017 were retrospectively analyzed. Among them, 83 cases were treated with epirubicin + cyclophosphamide + 5-fluorouracil (CEF group), 75 cases with epirubicin + cyclophosphamide + docetaxel (TEC group), with 3 cycles of chemotherapy. The efficacy and adverse reactions of the two NAC regimens were compared and analyzed. Tissue specimens were collected before and 10 days after the administration of chemotherapy in order to detect the expression of ANXA3 by qRT-PCR in each group. RESULTS: There were significant differences in the rates of complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) between the two groups (z=10.716, p=0.013). The clinical effectiveness rate in the TEC group was significantly higher than that in the CEF group (p<0.05). There was no difference in the pathology grade between the two groups (p>0.05); however, the pathological effective rate in the TEC group was significantly higher than that in the CEF group (p<0.05). There was no difference in the rate of bone marrow suppression between the two groups (p>0.05). While there was no difference in the relative expression of ANXA3 between the two groups before chemotherapy, the relative expression of ANXA3 in the TEC group was lower than that in the CEF group after NAC (p<0.05). The relative expression in both groups after chemotherapy was lower than that before NAC (P<0.05). CONCLUSION: Compared with CEF regimen, NAC with TEC regimen can improve the clinical and pathological effectiveness rate, inhibit the expression of ANXA3, and improve the prognosis of patients, thus having a certain application prospect in NAC.


Assuntos
Anexina A3/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Taxoides/administração & dosagem , Taxoides/efeitos adversos
20.
Brain Behav ; 9(6): e01312, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31063261

RESUMO

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant and difficult to manage side effect of neurotoxic chemotherapies. Several risk factors for CIPN have been identified to date, but inconsistencies and methodological limitations exist in past research. Also, a limited number of potential risk factors has been investigated in the past. AIM: The objective of this study was to assess the relative contribution of a wider range of risk factors in the development of CIPN. METHODS: This analysis used the 6-month data after starting chemotherapy from a larger prospective observational study on CIPN risk, prevalence, and quality of life. Patients were assessed at recruitment for possible CIPN risk factors, including prior history of neuropathies, current/past infectious diseases; neurotoxic medication history; personal and treatment characteristics; smoking history, alcohol use, and vegetable/fruit intake. Neuropathy was assessed at 6-months after starting chemotherapy with the neuropathy (motor/sensory) items of the NCI-CTCAE scale and the WHO criterion for neuropathy. Data on symptom burden were also collected. RESULTS: Data were available from 255 patients from three cancer centers in Hong Kong, Singapore, and UK. The use of different scales did not always identify the same predictor variables. Key risk factors in multivariate regression models included older age (highest OR = 1.08, p < 0.01 with the WHO scale), chemotherapy (platinum-based chemotherapy had OR = 0.20-0.27 in developing CIPN compared to taxane-based chemotherapy), history of neuropathy (for motor CIPN only, OR = 8.36, p < 0.01), symptom burden (OR = 1.06, p < 0.05), number of chemotherapy cycles received (OR = 1.19-1.24, p < 0.01), and alcohol intake (OR = 0.32, p < 0.05). In univariate analysis, the use of statins was implicated with CIPN (p = 0.03-0.04 with different assessments) and diabetes showed a trend (p = 0.09) in the development of CIPN. CONCLUSION: This study confirmed the CIPN risk related to certain variables and identified new ones. This knowledge can assist with treatment decisions and patient education.


Assuntos
Antineoplásicos/efeitos adversos , Síndromes Neurotóxicas/etiologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Institutos de Câncer , Cisplatino/efeitos adversos , Docetaxel/efeitos adversos , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Platina/efeitos adversos , Prevalência , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Taxoides/efeitos adversos
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