RESUMEN
PURPOSE: We hypothesized that eribulin combined with cyclophosphamide (EC) would be an effective combination with tolerable toxicity for the treatment of advanced breast cancer (ABC). METHODS: Patients with histologically confirmed metastatic or unresectable ABC with any number of prior lines of therapy were eligible to enroll. In the dose escalation cohort, dose level 0 was defined as eribulin 1.1 mg/m2 and cyclophosphamide 600 mg/m2, and dose level 1 was defined as eribulin 1.4 mg/m2 and cyclophosphamide 600 mg/m2. Eribulin was given on days 1 and 8 and cyclophosphamide on day 1 of a 21-day cycle. In the dose expansion cohort, enrollment was expanded at dose level 1. The primary objective was clinical benefit rate (CBR), and secondary objectives were response rate (RR), duration of response (DOR), progression-free survival (PFS), and safety. RESULTS: No dose-limiting toxicities were identified in the dose escalation cohort (n = 6). In the dose expansion cohort, an additional 38 patients were enrolled for a total of 44 patients, including 31 patients (70.4%) with hormone receptor-positive (HR +)/HER2- disease, 12 patients (27.3%) with triple-negative breast cancer (TNBC), and 1 patient (2.3%) with HR + /HER2 + disease. Patients had a median age of 56 years (range 33-82 years), 1 prior line of hormone therapy (range 0-6), and 2 prior lines of chemotherapy (range 0-7). CBR was 79.5% (35/44; 7 partial response, 28 stable disease) and the median DOR was 16.4 weeks (range 13.8-21.1 weeks). Median PFS was 16.4 weeks (95% CI: 13.8-21.1 weeks). The most common grade 3/4 adverse event was neutropenia (47.7%, n = 21). Fourteen of 26 patients (53.8%) with circulating tumor cell (CTC) data were CTC-positive ([Formula: see text] 5 CTC/7.5 mL) at baseline. Median PFS was shorter in patients who were CTC-positive vs. negative (13.1 vs 30.6 weeks, p = 0.011). CONCLUSION: In heavily pretreated patients with ABC, treatment with EC resulted in an encouraging CBR of 79.5% and PFS of 16.4 weeks, which compares favorably to single-agent eribulin. Dose reduction and delays were primarily due to neutropenia. The contribution of cyclophosphamide to eribulin remains unclear but warrants further evaluation. NCT01554371.
Asunto(s)
Neoplasias de la Mama , Neutropenia , Policétidos Poliéteres , Neoplasias de la Mama Triple Negativas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Ciclofosfamida/efectos adversos , Furanos/uso terapéutico , Cetonas/efectos adversos , Neutropenia/tratamiento farmacológico , Receptor ErbB-2 , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/etiologíaRESUMEN
Organophosphates cause hyperstimulation of the central nervous system, leading to extended seizures, convulsions, and brain damage. Sarin is a highly toxic organophosphate nerve agent that has been employed in several terrorist attacks. The prolonged toxicity of sarin may be enhanced by the neuroinflammatory response initiated by the inflammasome, caspase involvement, and generation/release of proinflammatory cytokines. Since neurodegeneration and neuroinflammation are prevalent in sarin-exposed animals, we were interested in evaluating the capacity of quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone (Q-VD-OPh), a pan caspase inhibitor to attenuate neuroinflammation following sarin exposure. To test this hypothesis, sarin-exposed C57BL/6 mice were treated with Q-VD-OPh or negative control quinolyl-valyl-O-methylglutamyl-[-2,6-difluorophenoxy]-methyl ketone, sacrificed at 2- and 14-day time points, followed by removal of the amygdala and hippocampus. A Bio-Rad 23-Plex cytokine analysis was completed on each tissue. The results suggest that exposure to sarin induced a dramatic increase in interleukin-1ß and 6 other cytokines and a decrease in 2 of the 23 cytokines at 2 days in the amygdala compared with controls. Q-VD-OPh attenuated these changes at the 2-day time point. At 14 days, six of these cytokines were still significantly different from controls. Hippocampus was less affected at both time points. Diazepam, a neuroprotective drug against nerve agents, caused an increase in several cytokines but did not have a synergistic effect with Q-VD-OPh. Treatment of sarin exposure with apoptosis inhibitors appears to be a worthwhile approach for further testing as a comprehensive counteragent against organophosphate exposure. SIGNIFICANCE STATEMENT: A pan inhibitor of caspases (Q-VD-OPh) was proposed as a potential antidote for sarin-induced neuroinflammation by reducing the level of inflammation via inflammasome caspase inhibition. Q-VD-OPh added at 30 minutes post-sarin exposure attenuated the inflammatory response of a number of cytokines and chemokines in the amygdala and hippocampus, two brain regions sensitive to organophosphate exposure. Apoptotic marker reduction at 2 and 14 days further supports further testing of inhibitors of apoptosis as a means to lessen extended organophosphate toxicity in the brain.
Asunto(s)
Clorometilcetonas de Aminoácidos , Agentes Nerviosos , Quinolinas , Sarín , Ratones , Animales , Sarín/toxicidad , Inhibidores de Caspasas/farmacología , Inhibidores de Caspasas/uso terapéutico , Enfermedades Neuroinflamatorias , Inflamasomas , Ratones Endogámicos C57BL , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Encéfalo , Citocinas , Agentes Nerviosos/farmacología , Caspasas , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Organofosfatos/farmacología , Cetonas/efectos adversosRESUMEN
Asthma is characterized by airway inflammation and remodeling. 2-Undecanone (methyl nonyl ketone), a volatile organic compound originating from Houttuynia cordata, has the potential to ameliorate inflammatory diseases. This study aimed to explore potential benefits of 2-undecanone in asthma. 2-Undecanone (100, 200, or 400 mg/kg) was administered intragastrically to ovalbumin (OVA)-challenged BALB/c mice. Lung tissues were collected to observe histopathological changes, and bronchoalveolar lavage fluid (BALF) was collected for the detection of inflammatory cells and cytokine production. The results showed that 2-undecanone ameliorated OVA-induced pathologic changes of lungs, including reducing inflammatory cell infiltration, goblet cell hyperplasia, and airway smooth muscle thickness. The number of inflammatory cells and the levels of IL-4, IL-5, IL-13, and IgE in BALF were decreased by 2-undecanone in asthmatic mice. Furthermore, abnormal activation of NF-κB pathway in lung tissues of asthmatic mice was impeded by 2-undecanone. In vitro, 2-undecanone (12.5, 25, or 50 µM) suppressed platelet-derived growth factor-BB-induced proliferation and migration of primary airway smooth muscle cells (ASMCs), and inhibited the switching of ASMCs from contractile phenotype to synthetic phenotype. Consistently, 2-undecanone blocked NF-κB activation in ASMCs. Collectively, 2-undecanone relieves asthma through alleviating airway inflammation and remodeling, and this beneficial effect is achieved by inhibiting NF-κB pathway.
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Asma , FN-kappa B , Animales , Ratones , FN-kappa B/metabolismo , Asma/inducido químicamente , Asma/tratamiento farmacológico , Cetonas/efectos adversos , Pulmón/metabolismo , Líquido del Lavado Bronquioalveolar , Inflamación/patología , Ratones Endogámicos BALB C , Modelos Animales de EnfermedadRESUMEN
Polycystic ovary syndrome (PCOS) is one of the most common female reproductive and metabolic disorders. The ketogenic diet (KD) is a diet high in fat and low in carbohydrate. The beneficial effects of KD intervention have been demonstrated in obese women with PCOS. The underlying mechanisms, however, remain unknown. The aim of the present study was to investigate the effects of a KD on both reproductive and metabolic phenotypes of dehydroepiandrosterone (DHEA)-induced PCOS mice. Female C57BL/6 mice were divided into three groups, designated Control, DHEA, and DHEA+KD groups. Mice of both Control and DHEA groups were fed the control diet, whereas DHEA+KD mice were fed a KD with 89%(kcal) fat for 1 or 3 weeks after PCOS mouse model was completed. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that KD treatment significantly increased blood ketone levels, reduced body weight and random and fasting blood glucose levels in DHEA+KD mice compared with DHEA mice. Glucose tolerance, however, was impaired in DHEA+KD mice. Ovarian functions were improved in some DHEAmice after KD feeding, especially in mice treated with KD for 3 weeks. In addition, inflammation and cell apoptosis were inhibited in the ovaries of DHEA+KD mice. Results from in vitro experiments showed that the main ketone body ß-hydroxybutyrate reduced inflammation and cell apoptosis in DHEA-treated KGN cells. These findings support the therapeutic effects of KD and reveal a possible mechanism by which KD improves ovarian functions in PCOS mice.
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Dieta Cetogénica , Síndrome del Ovario Poliquístico , Humanos , Ratones , Femenino , Animales , Síndrome del Ovario Poliquístico/metabolismo , Ratones Endogámicos C57BL , Fenotipo , Inflamación , Deshidroepiandrosterona , Cetonas/efectos adversos , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Neutropenia is a major dose-limiting toxicity of cancer chemotherapy. Semimechanistic mathematical models have been applied to describe the time course of neutrophil counts. The objectives of this study were to develop a mathematical model describing changes in neutrophil counts during eribulin treatment, to apply the empirical Bayes method to predict the probability of developing neutropenia ≥ grade 3 during eribulin treatment in each patient, and to propose the implementation of this mathematical tool in clinical practice for individual safety management. METHODS: The present model analysis and subsequent external evaluation were performed using the data of 481 patients with breast cancer, previously obtained from a postmarketing surveillance (training set) and a phase 2 clinical study (validation set). The model we previously reported (Kawamura et al 2018) was modified to improve its predictive capability. The individual time course of neutrophil changes during the treatment period was predicted by the empirical Bayes method using the observed neutrophil counts at baseline and the first measurement after the first eribulin dose. To evaluate the predictability of this method, the predicted neutrophil counts were compared with those of the observed values. RESULTS: The developed model provided good individual predictions, as indicated by the goodness-of-fit plots between the predicted and observed neutrophil counts, especially for a lower neutrophil count range. Days required to reach the nadir after the dose were also well-predicted. The sensitivity, specificity, and accuracy of the prediction of neutropenia grade ≥3 were 76%, 53%, and 71%, respectively. CONCLUSIONS: We developed a mathematical method for predicting and managing the risk of neutropenia during eribulin treatment. This method is generally applicable to other cases of chemotherapy-induced neutropenia and can be a new practical tool for individual safety management.
Asunto(s)
Neoplasias de la Mama , Neutropenia , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Teorema de Bayes , Cetonas/efectos adversos , Neutropenia/inducido químicamenteRESUMEN
PURPOSE: The aim of this study was to identify factors associated with progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer (MBC) treated with eribulin in a real-world setting, to improve information provision in those considering treatment. METHODS: Patients treated with eribulin for MBC at The Christie NHS Foundation Trust, Manchester, UK, between August 2011 and December 2018 were included (n = 439). Data were collected by retrospective review of medical records and electronic prescribing systems. Factors such as biological subtype, distant recurrence-free interval, previous lines of chemotherapy and the 'average duration of previous treatment lines' (ADPT) (calculated as: (date of initiation of eribulin-date of MBC) / the number of previous treatment lines in the metastatic setting) were evaluated for prognostic impact using Cox proportional hazards regression. RESULTS: In the full cohort, the median PFS and OS were 4.1 months (95% CI 3.7-4.4) and 8.6 months (95% CI 7.4-9.8), respectively. Outcomes were significantly inferior for those with triple-negative breast cancer (TNBC) (n = 92); PFSTNBC: 2.4 months (95% CI 2.1-3.0), p = < 0.001 and OSTNBC: 5.4 months (95% CI 4.6-6.6), p = < 0.001. ADPT was the only factor other than subtype significantly associated with PFS and OS. Longer ADPT was also significantly associated with PFS and OS in those with TNBC. For example, women in the lowest ADPT tertile (< 5.0 months) achieved a median OS of only 4.3 months, whereas those in the upper ADPT tertile (> 8.7 months) had a median OS of 12.1 months (p = 0.004). CONCLUSION: Our results indicate that the ADPT lines is an important factor when predicting the outcome with eribulin chemotherapy in a palliative setting and that quantitative guidance on the likely PFS and OS with treatment can be provided using ADPT. Validation in additional cohorts is warranted.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Furanos/uso terapéutico , Humanos , Cetonas/efectos adversos , Estudios Retrospectivos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
Adenoid cystic carcinoma (ACC) is a rare salivary glands tumor and often displays aggressive behavior with frequent relapse and metastasis. The terminal ACC lacks standard treatment guidelines and is always accompanied by poor prognosis. Here, we report a case of rare perianal ACC who received resection and palliative adjuvant radiation. Five years later, PET-computed tomography (CT) showed perianal recurrence and multiple pulmonary metastases. Combined chemotherapy with doxorubicin, carboplatin and cyclophosphamide was applied for two cycles but ineffective. Further next-generation sequencing analysis of perianal tissue demonstrated the v-myb avian myelobastosis viral oncogene homolog and nuclear factor I/B fusion gene and two novel BCL-6 corepressor (BCOR) mutations (p.F1106Tfs*5 and p.L1524Hfs*8). The therapy was switched to eribulin and anlotinib and has been performed for eight cycles. At recent follow-ups, MRI and CT examinations revealed the diminishing perianal and pulmonary lesions. This study presented the first case of perianal ACC with multiple pulmonary metastases and particular BCOR mutations, who presented a durable response to eribulin and anlotinib, providing a potential therapeutic option for advanced refractory ACC.
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Neoplasias de las Glándulas Anales/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Carcinoma Adenoide Quístico/tratamiento farmacológico , Furanos/uso terapéutico , Indoles/uso terapéutico , Cetonas/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Quinolinas/uso terapéutico , Neoplasias de las Glándulas Anales/patología , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Adenoide Quístico/patología , Furanos/administración & dosificación , Furanos/efectos adversos , Humanos , Indoles/administración & dosificación , Indoles/efectos adversos , Cetonas/administración & dosificación , Cetonas/efectos adversos , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Quinolinas/administración & dosificación , Quinolinas/efectos adversosRESUMEN
OBJECTIVE: Eribulin treatment improved overall survival with predictable toxicities in phase 3 trials of patients with previously treated, locally advanced/metastatic breast cancer. This study (NCT02443428) prospectively observed eribulin-treated patients in real-world clinical practice. METHODS: This observational multicentre registry study enrolled 76 patients with locally advanced/metastatic breast cancer who had ≤2 prior chemotherapeutic regimens for advanced disease. Eribulin was administered at a 1.23 mg/m2 dose (days 1 and 8 of every 21-day cycle). Adverse events (AEs) were monitored and effectiveness was assessed per local practice. RESULTS: AEs occurred in 98.7% of patients; 88.2% had eribulin-related AEs. The most common AEs were fatigue (64.5%), alopecia (36.8%), nausea (35.5%) and constipation (30.3%). Serious AEs occurred in 42.1% of patients. The most common grade 3/4 AEs were neutropenia (9.2%), febrile neutropenia (9.2%), dyspnoea (5.3%) and pleural effusion (5.3%). No fatal AEs occurred. Dose reductions occurred in 31.6% of patients, 42.1% experienced dose delays and 9.2% discontinued due to worsening condition. There were complete responses in 2.6% and partial responses in 15.8% of patients. Median time to progression and overall survival were 4.0 and 8.3 months, respectively. CONCLUSION: Eribulin was well tolerated in real-world clinical practice, comparable to safety and effectiveness reported in other clinical trials.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Furanos/efectos adversos , Cetonas/efectos adversos , Sistema de Registros , Resultado del TratamientoRESUMEN
Objective: To explore the efficacy and safety of real-world eribulin in the treatment of metastatic breast cancer. Methods: From December 2019 to December 2020, patients with advanced breast cancer were selected from Beijing Chaoyang District Sanhuan Cancer Hospital, Shandong Cancer Hospital, Peking University Cancer Hospital, Baotou Cancer Hospital, Shengjing Hospital Affiliated to China Medical University, and Cancer Hospital of Chinese Academy of Medical Sciences. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: The median progression-free survival (PFS) of 77 patients was 5 months, the objective response rate (ORR) was 33.8%, and the disease control rate (DCR) was 71.4%. The ORR of patients with triple-negative breast cancer was 23.1%, and the DCR was 57.7%; the ORR of patients with Luminal breast cancer was 40.0%, and the DCR was 77.8%; the ORR of patients with HER-2 overexpression breast cancer was 33.3%, and the DCR was 83.3%. ORR of 50.0% and DCR of 66.7% for patients treated with eribulin as first to second line treatment, ORR of 29.4% and DCR of 76.5% for patients treated with third to fourth line and ORR of 28.6% and DCR of 71.4% for patients treated with five to eleven line. The ORR of patients in the eribulin monotherapy group was 40.0% and the DCR was 66.0%; the ORR of patients in the combination chemotherapy or targeted therapy group was 22.2% and the DCR was 81.5%. Patients with a history of treatment with paclitaxel, docetaxel, or albumin paclitaxel during the adjuvant phase or after recurrent metastasis had an ORR of 32.9% and a DCR of 69.9% when treated with eribulin. The treatment efficacy is an independent prognostic factor affecting patient survival (P<0.001). The main adverse reactions in the whole group of patients were Grade â ¢-â £ neutrophil decline [29.9% (23/77)], and other adverse reactions were Grade â ¢-â £ fatigue [5.2% (4/77)], Grade â ¢-â £ peripheral nerve abnormality [2.6% (2/77)] and Grade â ¢-â £ alopecia [2.6% (2/77)]. Conclusions: Eribulin still has good antitumor activity against various molecular subtypes of breast cancer and advanced breast cancer that has failed multiple lines of chemotherapy, and the adverse effects can be controlled, so it has a good clinical application value.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama/patología , Femenino , Furanos/efectos adversos , Humanos , Cetonas/efectos adversos , Paclitaxel/efectos adversos , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
BACKGROUND: The recommended starting dose of eribulin in patients with hepatic impairment is based on the Child-Pugh score, largely informed by a pharmacokinetic study of 18 patients. In the pivotal studies of eribulin in metastatic breast cancer (Study 301 and Study 305 [EMBRACE]), entry criteria and dose modifications were based on liver-function test (LFT) results rather than Child-Pugh score. In populations such as patients with metastatic breast cancer, in which metastatic infiltration is the predominant cause of hepatic impairment, using Child-Pugh score may be problematic; in clinical practice, it has been more common for oncologists to make dosing decisions based on LFTs. To address this, the effects of abnormal baseline LFT results on eribulin efficacy and safety were investigated. METHODS: In this pooled post hoc analysis, 1062 patients who were randomized to receive eribulin in Studies 301 and 305 were divided into 4 groups: (A) no elevated LFT results (no liver impairment); (B) increased levels of aspartate aminotransferase and/or alanine aminotransferase; (C) decreased albumin and/or increased levels of aspartate aminotransferase and/or alanine aminotransferase but not increased bilirubin; and (D) increased bilirubin. Patients were subcategorized by presence of liver metastasis. Drug exposure, dose intensity, and treatment-emergent adverse events (TEAEs) were analyzed. RESULTS: Eribulin mesylate mean dosage was 0.82 (group A)-0.65 mg/m2/week (group D). Group D had shorter treatment, more dose reductions/delays, more TEAEs leading to dose modifications, and numerically lower objective response rates and clinical benefit rates versus groups A-C. TEAE rates leading to dose modification were similar between group D (45.5%) and groups A-C (range, 43.5-54.9%) in the absence of liver metastases, but higher in group D (91.3%) compared with groups A-C (range, 41.7-54.3%) if liver metastases were present. CONCLUSIONS: Mild elevations in bilirubin levels were associated with increased toxicity and a greater requirement for dose modifications. Based both on these study data and existing recommendations, we propose a novel scheme to guide initial dose selection in patients with metastatic breast cancer and hepatic impairment that is based on LFTs rather than Child-Pugh score.
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Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/fisiopatología , Furanos/administración & dosificación , Cetonas/administración & dosificación , Antineoplásicos/efectos adversos , Bilirrubina/sangre , Neoplasias de la Mama/patología , Relación Dosis-Respuesta a Droga , Femenino , Furanos/efectos adversos , Humanos , Cetonas/efectos adversos , Pruebas de Función Hepática , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/fisiopatología , Neoplasias Hepáticas/secundario , Guías de Práctica Clínica como Asunto , Transaminasas/sangre , Resultado del TratamientoRESUMEN
PURPOSE: Adverse events (AE) during oncology clinical trials are typically reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), which provides information about the frequency and severity of AEs from the provider's perspective. Instruments that track patient-reported outcomes (PRO) complement the CTCAE and provide additional patient-centered information about the toxicity profile of an anti-cancer drug. METHODS: We conducted a single-arm, open-label phase II study of eribulin as first- or second-line therapy for metastatic hormone receptor-positive/HER2-negative (HR+/HER2-) or triple-negative breast cancer (TNBC). Patients were recruited simultaneously into each cohort by tumor subtype. The primary endpoint was overall response rate (ORR). Secondary endpoints included evaluation of toxicity by CTCAE and PRO instruments and agreement between CTCAE and PRO. The study also investigated single-nucleotide polymorphisms (SNPs) associated with treatment-induced neurotoxicity. RESULTS: 83 patients were enrolled: 45 into the HR+/HER2- cohort and 38 into the TNBC cohort. The ORR was 35.6% (90% CI 24-39%) in the HR+/HER2- cohort and 13.2% (90% CI 5-26%) in the TNBC cohort. Stable disease as the best response was recorded in 55.1% of patients with HR+/HER2- disease and 60.5% with TNBC. Toxicity analysis revealed a discordance between CTCAE and PRO assessment in many patients, with a focus on fatigue, alopecia, and neuropathy. Pharmacogenomic analysis identified SNPs associated with treatment-induced peripheral neuropathy. CONCLUSIONS: Eribulin is active in HER2- breast cancer. This study reveals that provider-assessed AEs can vary greatly from patient experiences. Future studies should incorporate CTCAE and PRO instruments to improve reporting of treatment-related AEs. ClinicalTrials.gov Registration: NCT01827787.
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Antineoplásicos , Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Femenino , Furanos/efectos adversos , Humanos , Cetonas/efectos adversos , Receptor ErbB-2/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genéticaRESUMEN
Liposarcomas are rare tumors arising from adipocytic tissue and accounting for approximately 15-20% of all soft tissue sarcomas. Liposarcoma can be further classified into histopathological subtypes with variable chemosensitivity according to subtype. Decisions regarding management should be made on an individual basis, but surgery for localized disease and systemic chemotherapy remain the mainstay of treatment. Currently, only doxorubicin and trabectedin have robust Phase III data to support their use in the management of advanced liposarcoma. However, in the subgroup analysis of a Phase III trial comparing eribulin with dacarbazine, there was a greater than 7-month improvement in median overall survival in those treated with eribulin. There are also promising results from emerging studies in novel and targeted agents for the treatment of liposarcoma.
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Antineoplásicos/administración & dosificación , Liposarcoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/epidemiología , Antineoplásicos/efectos adversos , Ensayos Clínicos Fase III como Asunto , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Furanos/administración & dosificación , Furanos/efectos adversos , Humanos , Cetonas/administración & dosificación , Cetonas/efectos adversos , Liposarcoma/mortalidad , Recurrencia Local de Neoplasia/prevención & control , Supervivencia sin ProgresiónRESUMEN
PURPOSE: Polyether-ether-ketone (PEEK) implants are increasingly used for the reconstruction of craniomaxillofacial deformities, but limited data exist on their limitations or risk factors for complications associated with their use. The purpose of the present study was to identify risk factors for postoperative inflammatory complications (POICs) after the use of PEEK implants in craniomaxillofacial reconstruction. METHODS: A retrospective cohort study was conducted, incorporating all patients treated with patient-specific PEEK implants at the authors' institution from August 1, 2012 to June 30, 2019. The outcome variable was the presence of POICs. The potential predictor variables were demographic, medical, anatomic, and treatment related. Statistical analysis was performed using Fisher exact tests, t tests, and multivariable logistic regression analysis where appropriate. RESULTS: The 32 patients included in the study were composed of 68.8% men; mean age was 40.6 years. The PEEK implant was placed adjacent to the paranasal sinuses in 56.3% of patients. The indication for use was malar depression in 50.0%, orbital dystopia in 46.9%, forehead or skull defects in 21.9%, and mandibular contour deformities in 6.2%; 8 patients had more than 1 indication. The overall rate of POICs was 28.1%. Of the POICs, 66.7% were managed with incision and drainage, revision surgery, or removal and 33.3% were managed with outpatient wound care or antibiotics. Tobacco use, the presence of an intraoral incision, and the presence of multiple incisions were all associated with POICs. On multivariable analysis, tobacco use approached significance (odds ratio, 17.3 [95% confidence interval, 0.98 to 306.7]) and multiple incisions (odds ratio, 6.9 [95% confidence interval, 1.5 to 32.3]) had a statistically significant association with the occurrence of complications. CONCLUSIONS: The present study identified several variables potentially associated with complications after the use of PEEK implants in maxillofacial reconstruction. Consideration should be given in the preoperative evaluation when a smoker is identified and when multiple incisions are planned.
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Implantes Dentales , Adulto , Benzofenonas , Éteres , Femenino , Humanos , Cetonas/efectos adversos , Masculino , Polietilenglicoles/efectos adversos , Polímeros , Complicaciones Posoperatorias/etiología , Prótesis e Implantes/efectos adversos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The interference screw is the most popular device that fixes the graft for anterior cruciate ligament reconstruction, reducing the incidence of windshield effect and bungee effect. For the screw, either metallic, "bioresorbable," or polyetheretherketone (PEEK) material is available. PEEK is popular and extensively used due to its stability, biocompatibility, radiolucency, and elastic modulus. Rare relevant complications were reported, but here, we report two cases of extra-articular migrations of PEEK interference screw from the tibial tunnel after anterior cruciate reconstruction. CASE REPORT: An 18-year-old boy and a 56-year-old woman underwent anterior cruciate ligament reconstruction using a PEEK interference screw to fix the graft in the tibial tunnel. They suffered from screw extrusion from the tibial tunnel after 40 days and six months, respectively, with an incision rupture or palpable subcutaneous mass. They underwent a second operation and recovered well. CONCLUSIONS: The exact incidence of extra-articular migrations of PEEK interference screws is unknown, but it seems to be quite low; despite this and its uncertain cause, the negative effects caused by the PEEK material need to be considered.
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Reconstrucción del Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Adolescente , Ligamento Cruzado Anterior/diagnóstico por imagen , Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior/efectos adversos , Benzofenonas , Tornillos Óseos/efectos adversos , Femenino , Humanos , Cetonas/efectos adversos , Masculino , Persona de Mediana Edad , Polietilenglicoles , PolímerosRESUMEN
Tumor lysis syndrome (TLS) is a complication of cancer treatment that requires urgent intervention. It is extremely rare in the treatment of soft tissue sarcoma (STS) of the limbs or trunk, and there are currently no reports of TLS occurrence from eribulin therapy. We report the case of a 78-year-old woman with an undiffer-entiated pleomorphic sarcoma on the right buttock. We initiated chemotherapy with intravenous eribulin mesylate. Deterioration of renal function, mild hyperkalemia, hyperuricemia, hypocalcemia, and hyperphos-phatemia were confirmed on examination, suggesting the presence of TLS. We present an extremely rare case of TLS from eribulin for STS.
Asunto(s)
Antineoplásicos/efectos adversos , Furanos/efectos adversos , Cetonas/efectos adversos , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Síndrome de Lisis Tumoral/etiología , Anciano , Antineoplásicos/administración & dosificación , Nalgas , Resultado Fatal , Femenino , Furanos/administración & dosificación , Humanos , Cetonas/administración & dosificación , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Síndrome de Lisis Tumoral/diagnósticoRESUMEN
To systemically evaluate the efficacy and safety of Gingko Ketone Ester Dropping Pills in treating angina pectoris and co-ronary heart disease. CNKI, Wanfang, SinoMed, PubMed, Cochrane Library and EMbase databases were retrieved on computer, and the randomized clinical trial(RCT) on Gingko Ketone Ester Dropping Pills in treating angina pectoris and coronary heart disease, which were published from the database establishment to December 31, 2019, were comprehensively collected. Literature screening, data extraction and quality evaluation were conducted independently by two researchers according to inclusion and exclusion criteria. Literature methodology quality evaluation was conducted with use of the Cochrane Handbook 5.3.0(bias risk assessment tool). Meta-analysis was performed with RevMan 5.3.0 software. A total of 10 RCTs were included. The results of the Meta-analysis showed that as compared with conventional Western medicine alone, the application of Gingko Ketone Ester Dropping Pills combined with conventional Western medicine treatment further improved the total effective rate and electrocardiogram effect(RR=1.43,95%CI[1.20,1.71],P<0.000 1). There were statistically significant differences in the number of angina attacks, the duration of angina and the amount of nitroglycerin used. In terms of safety indicators, four studies reported adverse reactions in the experimental group, including facial flu-shing, tachycardia, dizziness, dyspnea, nausea and other symptoms. Based on the existing findings, in the treatment of angina pectoris and coronary heart disease, Gingko Ketone Ester Dropping Pills combined with conventional Western medicine can improve the clinical total effective rate, electrocardiogram effect, number of angina attacks, duration of angina and the amount of nitroglycerin used. However, in the included studies, due to some methodological quality problems which would impact the reliability of literature results more high-quality randomized controlled trials are still needed for further verification.
Asunto(s)
Enfermedad Coronaria , Medicamentos Herbarios Chinos , Angina de Pecho/tratamiento farmacológico , Enfermedad Coronaria/tratamiento farmacológico , Medicamentos Herbarios Chinos/efectos adversos , Ésteres , Ginkgo biloba , Humanos , Cetonas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Reproducibilidad de los ResultadosRESUMEN
Background Data on eribulin as the first- or second-line treatment in a clinical setting, especially the overall survival (OS) of patients, are scarce. Therefore, we assessed the effectiveness and safety of eribulin as the first-, second-, and third- or later-line treatments in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in Japan. Methods This multicenter, prospective, post-marketing, observational study enrolled patients from September 2014 to February 2016 in Japan and followed them for 2 years. Patients were categorized by eribulin use into the first-, second-, and third- or later-line treatment groups. Results Of 651 registered patients, 637 patients were included in the safety and effectiveness analysis. In all, first-, second-, and third or later-line treatment groups, median OS (95% confidence interval) were 15.6 (13.8-17.6), 22.8 (17.3-31.0), 16.3 (12.4-19.9), and 12.6 (11.2-15.1) months and time to treatment failure (TTF) (95% confidence interval) were 4.2 (3.7-4.4), 5.2 (3.7-5.9), 4.2 (3.7-5.1), and 3.8 (3.5-4.2) months, respectively. Prolonged TTF was associated with complications of diabetes and the development of peripheral neuropathy after eribulin treatment, according to multivariate Cox regression analysis. Grade ≥ 3 adverse drug reactions (ADRs) were reported in 61.7% of the patients. Neutropenia (49.5%) was the most common grade ≥ 3 ADR in all groups. Conclusions The effectiveness and safety results of eribulin as the first- or second-line treatment were favorable. Thus, these suggest eribulin may be a first-line treatment candidate for patients with HER2-negative advanced breast cancer in Japan.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Furanos/uso terapéutico , Cetonas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Pueblo Asiatico , Neoplasias de la Mama/mortalidad , Femenino , Furanos/efectos adversos , Humanos , Estimación de Kaplan-Meier , Cetonas/efectos adversos , Persona de Mediana Edad , Neutropenia/inducido químicamente , Neutropenia/mortalidad , Vigilancia de Productos Comercializados , Receptor ErbB-2 , Resultado del TratamientoRESUMEN
Rhabdomyosarcoma is the most common soft tissue sarcoma that typically occurs in children and adolescents and is rare in adults. Furthermore, as cardiac tumor is rare, adult cardiac rhabdomyosarcoma is a very rare entity. Here, we report the case of a 68-year-old woman with cardiac rhabdomyosarcoma who was successfully treated with eribulin. She presented with sudden loss of consciousness, which was attributed to the cardiac tumor. The tumor was resected by emergency surgery and was diagnosed as embryonal rhabdomyosarcoma. Although surgical treatment alleviated her symptoms, the residual tumor increased in size after surgery and required multimodal treatment. First-line chemotherapy with the vincristine, actinomycin D, and cyclophosphamide regimen had to be discontinued owing to adverse events, and thus eribulin was used as a second-line treatment. Eribulin was better tolerated and helped maintain a stable disease status for >18 months. This reported case of cardiac rhabdomyosarcoma is the first case to be successfully treated with eribulin over a relatively long period. Eribulin therapy may thus be a viable treatment alternative for rhabdomyosarcoma.
Asunto(s)
Furanos/uso terapéutico , Neoplasias Cardíacas/tratamiento farmacológico , Cetonas/uso terapéutico , Rabdomiosarcoma/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Furanos/efectos adversos , Neoplasias Cardíacas/patología , Neoplasias Cardíacas/cirugía , Humanos , Cetonas/efectos adversos , Rabdomiosarcoma/patología , Rabdomiosarcoma/cirugía , Vincristina/uso terapéuticoRESUMEN
Due to its low incidence, liposarcoma displays a limited number of therapeutic options. However, eribulin recently received approval for the treatment of advanced liposarcoma patients, progressing to at least two chemotherapy lines. We report herein the case of a man initially diagnosed with a leyomiosarcoma, subsequently reclassified as a dedifferentiated liposarcoma, who received eribulin after he failed several therapy lines. Eribulin provided our patient an 8-month disease control and a substantial clinical benefit with no relevant adverse effects, showing a good efficacy and safety profile despite its delayed employ. Additionally, this case strengthens the pivotal importance of molecular profiling in the management of soft tissue sarcomas.
Asunto(s)
Antineoplásicos/uso terapéutico , Furanos/uso terapéutico , Cetonas/uso terapéutico , Leiomiosarcoma/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Biomarcadores de Tumor , Diagnóstico Tardío , Errores Diagnósticos , Furanos/administración & dosificación , Furanos/efectos adversos , Variación Genética , Humanos , Cetonas/administración & dosificación , Cetonas/efectos adversos , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/etiología , Leiomiosarcoma/mortalidad , Masculino , Persona de Mediana Edad , Retratamiento , Tiempo de Tratamiento , Tomografía Computarizada por Rayos XRESUMEN
We report the case of a 51 year-old patient affected by an advanced uterine leiomyosarcoma treated with eribulin as fourth-line therapy. The patient, with a previous history of leiomyomas of the myometrium, had undergone total hysterectomy for repeated metrorrhagias. After 7 years, metastases in the liver, bone and lung were documented. A fine needle liver biopsy demonstrated leiomyosarcoma metastasis. The patient was treated with first-line doxorubicin chemotherapy; after six cycles, disease progression was observed. A second-line trabectedin chemotherapy and a third-line gemcitabine chemotherapy were performed; no objective responses were seen after two cycles. The patient was then treated with eribulin on the basis of an EORTC Phase II trial showing preliminary activity in uterine leiomyosarcoma. After six cycles, CT scan showed partial remission of liver lesion. Disease progression was observed after nine cycles with eribulin, without severe side effects and preserving a good quality of life.