STAT3 inhibitor BBI608 reduces patient-specific primary cell viability of cervical and endometrial cancer at a clinical-relevant concentration

Aberrant activation of STAT3 signal pathway promotes tumor progression in many solid tumor types, including cervical cancer and endometrial cancer. BBI608, the STAT3 inhibitor had been reported in previous studies for restraining cancer stem cells. However, whether BBI608 is available for inhibiting the proliferation of cervical cancer or endometrial cancer remains poorly understood. This study investigated the anti-tumor effect and molecular mechanism of BBI608 on the patient-specific primary cells (PSPC) generated from cervical and endometrial cancer in vitro. Methods PSPCs were obtained from four patients via biopsy. The cell viability was analyzed by the CCK8 assay. The PSPCs were treated with various concentrations of BBI608 or/and paclitaxel; and then, western blot was applied to investigate the expression of phosphorylated STAT3 (pSTAT3). Results The PSPCs cell viability was reduced after treated with BBI608 at a lower concentration. Western blot results showed a reduction trend of pSTAT3 after PSPCs treated with BBI608. Our results demonstrated that BBI608 at the certain concentrations worked well in reducing the cell viability of PSPC from the patients who suffered from cervical cancer and endometrial cancer. Conclusions In this study, the patient-specific primary cell (PSPC) was used as the pre-clinical model for investigating the efficiency of BBI608 in reducing cancer cells viability. BBI608, at a clinical-relevant concentration, had valid efficiency in PSPCs from the patients. The dose of drugs treatment and the measured results were more valuable for further guiding clinical trials (AU)

Inclusion of cancer-associated fibroblasts in drug screening assays to evaluate pancreatic cancer resistance to therapeutic drugs

Pancreatic ductal adenocarcinoma (PDAC) is characterised by a pro-inflammatory stroma and multi-faceted microenvironment that promotes and maintains tumorigenesis. However, the models used to test new and emerging therapies for PDAC have not increased in complexity to keep pace with our understanding of the human disease. Promising therapies that pass pre-clinical testing often fail in pancreatic cancer clinical trials. The objective of this study was to investigate whether changes in the drug-dosing regimen or the addition of cancer-associated fibroblasts (CAFs) to current existing models can impact the efficacy of chemotherapy drugs used in the clinic. Here, we reveal that gemcitabine and paclitaxel markedly reduce the viability of pancreatic cell lines, but not CAFs, when cultured in 2D. Following the use of an in vitro drug pulsing experiment, PDAC cell lines showed sensitivity to gemcitabine and paclitaxel. However, CAFs were less sensitive to pulsing with gemcitabine compared to their response to paclitaxel. We also identify that a 3D co-culture model of MIA PaCa-2 or PANC-1 with CAFs showed an increased chemoresistance to gemcitabine when compared to standard 2D mono-cultures a difference to paclitaxel which showed no measurable difference between the 2D and 3D models, suggesting a complex interaction between the drug in study and the cell type used. Changes to standard 2D mono-culture-based assays and implementation of 3D co-culture assays lend complexity to established models and could provide tools for identifying therapies that will match clinically the success observed with in vitro models, thereby aiding in the discovery of novel therapies. (AU)

Quimioterapia nanométrica a base de cannabinoides para el tratamiento de tumores ginecológicos / Cannabinoid based chemo-nanotherapy for the treatment of gynecological malignancies

El cannabidiol está despertando un creciente interés como agente antitumoral. Sin embargo, no se ha estudiado su efecto en cáncer de ovario, uno de los tumores más agresivos en mujeres. En el presente trabajo se ha evaluado, por primera vez, el potencial uso del cannabidiol en solución y encapsulado en nanopartículas funcionalizadas con ácido fólico en cáncer de ovario, ya que estos tumores sobreexpresan los receptores de ácido fólico, permitiendo una acumulación selectiva de estas nanoformulaciones en las células tumorales. El cannabidiol en solución inhibe la proliferación y migración de las células SKOV-3. En terapia de combinación, aumenta significativamente la eficacia antitumoral del paclitaxel, presentando un efecto sensibilizador y sinérgico. En los modelos in ovo, la administración previa de cannabidiol en solución seguido de su coadministración con paclitaxel muestra un efecto inhibitorio sobre el crecimiento tumoral significativamente superior al paclitaxel en monoterapia. Las nanopartículas desarrolladas son eficazmente internalizadas por las células SKOV-3, presentando las nanopartículas con ácido fólico una captación más rápida. Aunque en los estudios de eficacia antitumoral in vitro las nanopartículas funcionalizadas no presentan una actividad antiproliferativa superior al cannabidiol en solución o a las nanopartículas no funcionalizadas, en los modelos in ovo su eficacia antitumoral es significativamente superior, indicando que el desarrollo de nanopartículas funcionalizadas con ácido fólico es una buena estrategia para vectorizar el cannabidiol a tumores de ovario. Por último, las nanopartículas de cannabidiol potencian el efecto antitumoral del paclitaxel, presentando las formulaciones funcionalizadas con ácido fólico una mayor eficacia que el cannabidiol en solución. (AU)

Cannabidiol has become in a potential anticancer agent. Nevertheless, it has not been evaluated in ovarian cancer, one of the most aggressive tumors in women. In this work, the potential use of cannabidiol in solution and encapsulated into polymeric nanoparticles coated with folic acid was evaluated for the first time for the treatment of ovarian cancer. Ovarian tumors over-express folic acid receptors and folic-acid-coated nanoformulations trend to be selectively accumulated at tumor site. Cannabidiol in solution administered as monotherapy inhibits the proliferation and migration of SKOV-3 cells. In combination therapy, it significantly increases the antitumor efficacy of paclitaxel, showing a sensitizer and synergistic effect. In ovo, the previous administration of cannabidiol in solution followed by its co-administration with paclitaxel, shows a significantly higher inhibitory effect on ovarian tumor growth than single paclitaxel. The developed nanoparticles are efficiently uptaken by SKOV-3 cells, showing folic acid coated formulations a faster internalization. Although coated formulations do not exhibit a higher in vitro antiproliferative effect compared to cannabidiol in solution or non-coated formulations, in ovo its antitumoral efficacy is significantly higher. This indicates thatfolic acid-coated nanoparticles represent a good strategy to target cannabidiol to ovarian tumors. Finally, cannabidiol-loaded nanoparticles improve the in vitro antiproliferative effect of paclitaxel, showing folic acid-coated-formulations a better efficacy than cannabidiol in solution. (AU)

Establishment of an acquired lorlatinib-resistant cell line of non-small cell lung cancer and its mediated resistance mechanism

Although lorlatinib, the third generation of echinoderm microtubule protein 4-anaplastic lymphoma kinase (EML4-ALK) tyrosine kinase inhibitor (TKI), overcame the previous generation ALK-TKIs’ drug resistance problems, but the mechanism of lorlatinib resistance remained unclear. Furthermore, optimal chemotherapy for lorlatinib-resistant non-small cell lung cancer (NSCLC) patients was still unknown.MethodsA lorlatinib-resistant NSCLC cell line SNU-2535LR was generated by gradually increasing dose of lorlatinib to crizotinib-resistant cell line SNU-2535 in vitro. To study the resistance mechanism of SNU-2535LR cells, we applied CCK-8 assay to detect the sensitivity of crizotinib and the reverse effect of APR-246, a p53 activator, on lorlatinib-induced resistance and different chemotherapy drugs to SNU-2535LR cells. We also detected the expressions of EML4-ALK-related proteins of SNU-2535LR cells via western blot.Please confirm that author names have been identified correctly and are presented in the right order. (AU)

Tumor-associated macrophages (TAMs) modulate response to HER2-targeted agents in a humanized mouse model of breast cancer

PurposeTumor-associated macrophages (TAM) may participate to antitumor activity of anti-HER2-targeted therapies (Pertuzumab, Trastuzumab) in breast cancers harbouring HER-2 overexpression through antibody-dependent phagocytosis. Additive antitumor effect of concurrent cytotoxic chemotherapies, including Paclitaxel, may be counterbalanced by alteration in TAM infiltrate. The aim of this study is to evaluate the role of TAM in tumor response to anti-HER2-targeted therapies and chemotherapy in an experimental model of HER2-amplified breast cancer.MethodsA xenograft mouse model was built by subcutaneous injection of the SKBR-3 human HER2-amplified breast cancer cell line in Hu-CD34+ mice. Animals were randomized to receive weekly administration of Cremophor (control), Trastuzumab+Pertuzumab (TP), and Paclitaxel+Trastuzumab+Pertuzumab (PTP) with or without macrophage depletion with clodronate (C). At week 4, mice were euthanised and tumors were harvested for immunohistochemical analysis of TAM infiltration (RBP-J CD163 and CD68 for M1, M2, and overall TAM, respectively).ResultsTumor size was significantly lower in mice treated with TP, PTP, and PTP+C as compared to control, while no meaningful difference was observed in the TP+C arm. Analysis of TAM infiltrate showed significantly lower CD68 and CD163 expression in PTP, TP+C, and PTP+C as compared to TP and control arm. RBP-J expression was significantly decreased in mice treated with clodronate depletion.ConclusionsActivity of TP is modulated by TAM infiltrate, that is inhibited by concurrent administration of Paclitaxel. To enhance the effect of anti-HER2-targeted therapies and minimize chemotherapy-related side effects, modulation of TAM should be considered in novel therapeutic combinations.

Nepafenaco para edema macular cistoideo secundario a paclitaxel / Nepafenac for cystoid macular oedema secondary to paclitaxel

El paclitaxel es utilizado para tratar una amplia gama de tumores malignos. Se sabe que estos fármacos causan efectos adversos oculares, siendo el edema macular cistoide una complicación conocida pero rara de esta terapia. Aunque la mayoría de los casos se resuelven después de la interrupción del fármaco, varios autores han intentado diversos tratamientos para acelerar la resolución o cuando la terapia con paclitaxel no puede suspenderse. Presentamos un caso de un varón de 62 años que presentó disminución de la agudeza visual debido a edema macular cistoideo bilateral después de la administración de paclitaxel para cáncer de esófago; como parte del estudio se realizó angiografía por tomografía de coherencia óptica en el momento del diagnóstico y posteriormente cuando el cuadro remitió. Como tratamiento se prescribió colirio de nepafenaco (AU)

Paclitaxel is used to treat a wide range of malignant tumours. This type of drug is known to cause ocular adverse effects, with cystoid macular oedema being a known, but rare complication, of this therapy. Although most cases resolve after discontinuation of the drug, several authors have attempted various treatments to accelerate resolution, or when paclitaxel therapy cannot be discontinued. A case is presented of a 62 year-old man who presented with decreased visual acuity due to bilateral cystoid macular oedema after administration of paclitaxel for oesophageal cancer. As part of the study, optical coherence tomography angiography (OCTA) was performed at the time of diagnosis, and later when the symptoms subsided. Nepafenac eye drops were prescribed as treatment (AU)

Sequential chemotherapy regimen of induction with panitumumab and paclitaxel followed by radiotherapy and panitumumab in patients with locally advanced head and neck cancer unfit for platinum derivatives. The phase II, PANTERA/TTCC-2010-06 study

Background Sequential treatment of Panitumumab (Pb) plus Paclitaxel (Px) as induction treatment (IT) followed by concurrent bioradiotherapy (Bio–RT) with Pb may be an alternative for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) in patients ineligible for high-dose cisplatin therapy. Methods Phase II, single-arm, multicentre study, with two-stage design, in patients ≥ 18 years with stage III–IVa–b LA-SCCHN unfit for platinum. Patients received Px + Pb (9 weeks) as IT followed by Bio–RT + Pb. Primary endpoint: overall response rate (ORR) after IT, defined as: more than 70% of patients achieving complete response (CR) or partial response (PR) to IT. Secondary end-points: progression-free survival, organ preservation rate, safety profile. Results Study ended prematurely (51 patients) due to slow recruitment. ORR: 66.7% (95% CI: 53.7–79.6), 8 (15.7%) CR and 26 (51.0%) PR. 39 patients (76%) completed radiotherapy (RT). Pb and/or Px-related adverse events (AEs) grade 3–4: 56.9% during IT and 63.4% during the concomitant phase, of which most common were skin toxicity (33.3%). Five deaths occurred during treatment, two of them (3.9%) were Pb and/or Px-related. Conclusions Although underpowered, ORR was higher than the pre-specified boundary for considering the treatment active. Although Px + Pb as IT provides some benefit, the safety profile is worse than expected. To consider Pb + Px as IT as an alternative for platinum-unsuitable LA-SCCHN, further research/investigation would be needed (AU)

Clinical outcomes of FOLFIRINOX and gemcitabine–nab paclitaxel for metastatic pancreatic cancer in the real world setting

Background/objectives The incidence of pancreatic cancer is increasing in developed countries. The incorporation of new therapies, to the first-line treatment of patients with good performance status led to better survival in clinical trials. However, there is a wide variability in their use and some concerns about the treatment of elderly patients who were not included in the clinical trials. Methods This is a retrospective multicenter study. Data from consecutive patients diagnosed with metastatic pancreatic cancer (mPC) treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) were analysed to evaluate efficacy (overall survival—OS) and toxicity. Results A total of 119 patients were included. 49.6% were treated with FFX and 50.4% with GNP in first-line. The median OS was 12 months with no statistically significant differences between both regimens (12.7 m for FFX vs 10.2 m for GnP). Elevated Ca 19.9 levels and neutrophil–lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70-y. 54% patients received a second-line treatment, 56% in the FFX group and 44% in the GnP group. The median OS for patients older than 70 was 9.5 m versus 12.3 m for patients younger than 70. Progression of the disease was the cause of death in 67.6% of the patients. Conclusions In our setting, the use of FFX and GnP for treating mPC is quite similar, but superiority could not be demonstrated for any of the schemes in the first line. OS was determined by basal levels of Ca 19.9 and NLR. Patients receiving both regimens in first/second line whichever the sequence, exhibited the best survival rates. In our series, elderly patients had poorer survival rates (AU)

Computed tomography reconstruction for evaluating response in axillary lymph nodes of breast cancer after neoadjuvant chemotherapy

Purpose To assess the performance of computed tomography (CT) reconstruction in evaluating the response in metastatic lymph nodes after neoadjuvant chemotherapy (NAC) in breast cancer patients. Methods Patients undergoing pre-NAC and post-NAC CT were identified from the Peking University Cancer Hospital database. Axillary Lymph nodes (ALNs) that shrunk to < 5 mm in short-axis diameter after NAC on CT reconstruction images were classified as clinical complete response. Evaluations of CT reconstruction on ALNs were correlated with residual nodal disease in the final pathology. Overall, 53 invasive breast cancer patients between October 2016 and March 2018 were eligible for our study. The median age was 48 (range 35–70) years. Most women presented with T2 tumors (35/53, 66.0%). Results After NAC, 20 (37.7%) patients without residual nodal disease were defined as pCR. Of 53 patients, 18 (33.9%) showed negative conversion of ALNs on CT reconstruction evaluation; axillary pCR was present in 16/18 (88.9%) patients. Among 35 patients with abnormal nodes on post-NAC CT reconstruction, 31 (88.6%) had axillary metastasis on the final pathology. The sensitivity and specificity of CT reconstruction in predicting node-negative status were 80.0% and 93.9%, respectively. The positive predictive value was 84.9% for lymph node pCR. The area under the receiver operating characteristic curve of each imaging modality was 0.870 (95% confidence interval 0.755–0.984). Conclusions CT reconstruction was useful for evaluating ALNs response following NAC and may be used to predict axillary nodes’ pCR with adequate accuracy (AU)

Edema macular asociado a taxanos: presentación de un caso y revisión de la literatura / Macular oedema associated with taxanes: A case report and literature review

ANTECEDENTES Y OBJETIVO: Los taxanos son un grupo de quimioterápicos frecuentemente utilizados que, aunque rara vez, pueden dar lugar a un edema macular. El objetivo de este artículo es revisar y comunicar, de forma integrada, los datos de los casos previamente comunicados en la literatura, así como presentar un nuevo caso. MATERIAL Y MÉTODOS: Revisión narrativa de publicaciones de casos de edemas maculares en relación con taxanos, y presentación del caso clínico de una mujer de 73 años que, tras el tratamiento con paclitaxel por un cáncer de mama metastásico, desarrolla un edema macular que cede tras suspenderse el fármaco. RESULTADOS: Se incluyeron 57 casos que contienen los datos de 109 ojos recogidos en 52 artículos. El 76,79% de los casos fueron mujeres y la edad media fue de 58,75 años. El cáncer que más frecuentemente motivó el tratamiento fue el de mama (60,72%) y el 92,5% de los casos presentaba metástasis. El fármaco asociado con mayor frecuencia fue el paclitaxel (52,63%). La mediana del tiempo transcurrido hasta el desarrollo de síntomas fue de 4,25 meses. En la exploración inicial, el 92,86% de los casos presentó un edema bilateral y la agudeza visual media fue 0,4 (escala decimal), el grosor macular medio 509,63 micras, y el 97,83% de los ojos no presentaron hallazgos angiográficos o fueron mínimos. En el 90,57% de los casos el tratamiento con taxanos fue interrumpido, y algún otro tratamiento fue empleado en un 43,86% de los casos, siendo el más usado la acetazolamida. La evolución fue favorable, en mayor o menor medida, en el 96,23% de los casos. CONCLUSIONES: A pesar de ser una entidad rara, el edema macular asociado al uso de taxanos es una patología que todo oncólogo y oftalmólogo debiera conocer, teniendo en cuenta la buena evolución del cuadro que suele suceder a la suspensión del tratamiento

BACKGROUND AND PURPOSE: Although taxanes are a frequently used group of chemotherapy agents, they can, rarely, lead to macular oedema. The purpose of this article is to review and communicate, in an integrated way, the data of the cases previously reported in the literature, as well as to present a new case. MATERIAL AND METHODS: Narrative review of reports of cases of macular oedema associated with taxanes, and communication of the clinical case of a 73-year-old woman who, after treatment with paclitaxel for metastatic breast cancer, developed macular oedema that disappeared after discontinuing the drug. RESULTS: The review included 57 cases with data from 109 eyes collected in 52 articles. The large majority (76.79%) of the cases were women, and the mean age was 58.75 years. The cancer that most frequently motivated the treatment was breast cancer (60.72%), and 92.5% of cases had metastases. The most frequently associated drug was paclitaxel (52.63%). The median time to symptom development was 4.25 months. At the initial examination, 92.86% of the cases had bilateral oedema and the mean visual acuity was 0.4 (decimal scale). The mean macular thickness was 509.63 microns, and 97.83% of the eyes had no or minimal angiographic findings. In 90.57% of the cases, the treatment with taxanes was interrupted, and some other treatment was used in 43.86% of the cases, with the most widely used being acetazolamide. The outcome was favourable, to a greater or lesser extent, in 96.23% of cases. CONCLUSIONS: Despite being a rare entity, macular oedema associated with the use of taxanes is a disorder that every oncologist and ophthalmologist should be aware of, taking into account the good outcome of the condition that usually occurs when treatment is suspended

Mortalidad a largo plazo asociada al uso de dispositivos liberadores de paclitaxel en el tratamiento del paciente con enfermedad arterial periférica (informe de situación, junio de 2019) / Long term mortality signal associated to treatment with paclitaxel-eluting devices in peripheral arterial disease (status report, June 2019

Se resumen a continuación las principales reacciones y eventos de interés que se han venido produciendo en la comunidad vascular internacional desde el pasado mes de diciembre de 2018, cuando se publicó el metaanálisis de Konstantinos Katsanos, hasta junio de 2019. Este estudio, que ha sido severamente criticado, identifica la falta de fiabilidad de los resultados comunicados por la industria. A la luz de los datos hasta ahora expuestos, la SEACV hace una serie de recomendaciones basadas en la información disponible hasta ahora sobre los balones y stent farmacoactivos con paclitaxel que están en la misma línea que los organismos internacionales

This paper summarizes the main reactions and events of interest that have been occurring in the international vascular community since last December 2018, when the meta-analysis by Konstantinos Katsanos was published. This study, which has been severely criticized, identifies the unreliability of the results reported by the industry. In light of the data presented so far, the SEACV makes a series of recommendations about the paclitaxel-eluting balloons and stents based on the information available until now which are in line with international organizations

Reflexión y prudencia: paclitaxel en el tratamiento de la enfermedad de la arteria femoral superficial / Reflection and prudence: paclitaxel in the treatment of superficial femoralartery disease

No disponible

Edema facial recurrente / Recurrent Facial Edema

No disponible

Paclitaxel-induced cutaneous change mimicking malignancy in a previous cutaneous eruption / Alteración cutánea inducida por paclitaxel simulando malignidad sobre una erupción cutánea previa

Taxanes are antineoplastic drugs that can cause dermatotoxicity which can mimic an intraepidermal carcinoma. A 65-year-old woman presented with a cutaneous eruption suggestive of a paraneoplastic syndrome. Imaging studies showed multiple peritoneal nodules and associated ascites. A sample taken from the greater omentum revealed an adenocarcinoma. Clinical data and family history pointed to a gynecological origin of the tumor and the patient was treated with carboplatin and paclitaxel. A new cutaneous biopsy showed that the epidermis was acanthotic with atypical keratinocytes, abundant mitoses, and apoptotic figures, arising concerns of malignancy. According to the Plummer and Shea criteria, the lesion was ultimately interpreted as reactive cutaneous hyperplasia and expression of the taxane effect. We report, for the first time, paclitaxel-induced histologic changes on a previous cutaneous eruption. Pathologists should be aware of the profound cytopathic effects of taxane therapy in order to interpret skin biopsies of patients undergoing this treatment

Los taxanos son fármacos antineoplásicos que pueden causar dermatotoxicidad simulando un carcinoma intraepidérmico. Una mujer de 65 años se presentó con una erupción cutánea sugestiva de síndrome paraneoplásico. Los estudios de imagen mostraron múltiples nódulos peritoneales y ascitis asociada. Una muestra tomada del epiplón mayor reveló un adenocarcinoma. Teniendo en cuenta los datos clínicos y la historia familiar se asumió un origen ginecológico del tumor, y la paciente fue tratada con carboplatino y paclitaxel. Una nueva biopsia cutánea mostró que la epidermis era acantótica con queratinocitos atípicos, abundantes mitosis y figuras apoptóticas. Estos hallazgos levantaron la sospecha de malignidad. De acuerdo con los criterios de Plummer y Shea la lesión fue finalmente interpretada como hiperplasia reactiva epidérmica y expresión del efecto taxano. Presentamos por primera vez los cambios inducidos por paclitaxel sobre una erupción cutánea previa. Los patólogos deberían estar al tanto de los profundos efectos citopáticos de la terapia con taxanos con el fin de interpretar adecuadamente las biopsias cutáneas de los pacientes bajo este tratamiento

Incidencia y predictores de la reestenosis recurrente tras angioplastia con balón farmacoactivo en reestenosis de stents farmacoactivos: proyecto cooperativo ICARUS / Incidence and predictors of recurrent restenosis after drug-coated balloon angioplasty for restenosis of a drUg-eluting Stent: the ICARUS cooperation

Introducción y objetivos: No se ha estudiado bien la incidencia y los predictores de la reestenosis recurrente tras angioplastia con balón farmacoactivo (BFA) en reestenois de stents farmacoactivos (SFA). Nuestro objetivo es analizar la incidencia y los predictores de la reestenosis recurrente en los estudios aleatorizados en que se utilizaron BFA para el tratamiento de la reestenosis del SFA. Métodos: Los datos clínicos y anatómicos de los pacientes incluidos en 6 estudios aleatorizados sobre BFA para el tratamiento de reestenosis de SFA se analizaron en conjunto. Se asignó a todos los pacientes incluidos en este análisis a tratamiento con el BFA de paclitaxel SeQuent Please (B Braun; Melsungen, Alemania). El análisis se centró en los pacientes que tenían seguimiento angiográfico a los 6-9 meses. Se evaluó tanto la incidencia de reestenosis (definida como estenosis ≥ 50% del diámetro luminal en el análisis por segmento durante el seguimiento angiográfico tardío) como sus predictores clínicos y angiográficos. Resultados: Los datos de 546 pacientes se incluyeron en una única base de datos. De 484 pacientes (88,6%), con un total de 518 lesiones tratadas, se disponía de seguimiento angiográfico tardío, y se detectó recurrencia de reestenosis en 101 pacientes (20,8%). En el análisis multivariable, la longitud de la lesión (por cada incremento de 5 mm, OR = 1,58; IC95%, 1,10-2,26; p = 0,012) y el tamaño del vaso (por cada reducción de 0,5 mm, OR = 1,42; IC95%, 1,12-1,79; p = 0,003) se asociaron de manera independiente con la recurrencia de reestenosis. Conclusiones: Este estudio, el mayor disponible de pacientes tratados con BFA por reestenosis de SFA con seguimiento angiográfico tardío, demuestra que la recurrencia de reestenosis se produce en 1 de cada 5 de estos pacientes. Los predictores de la reestenosis recurrente son la longitud de la lesión y el tamaño del vaso

Introduction and objectives: The incidence and predictors of recurrent restenosis after drug-coated balloon (DCB) angioplasty for drug-eluting stent (DES) restenosis remain poorly studied. We sought to evaluate the incidence and predictors of recurrent restenosis among participants in randomized controlled trials receiving DCB angioplasty for DES restenosis. Methods: The clinical and lesion data of individuals enrolled in 6 randomized controlled trials of DCB angioplasty for DES restenosis were pooled. All patients included in this report were assigned to receive paclitaxel-coated balloon angioplasty with the SeQuent Please DCB (B Braun, Melsungen, Germany). The current analysis focused on participants with available follow-up angiography at 6 to 9 months. The incidence of recurrent restenosis, defined as diameter restenosis ≥ 50% in the in-segment area at follow-up angiography, and its clinical and angiographic predictors were evaluated. Results: A total of 546 patients were combined in a single dataset. Angiographic follow-up at 6 to 9 months was available for 484 patients (88.6%) with 518 treated lesions. Recurrent restenosis was detected in 101 (20.8%) patients. On multivariable analysis, lesion length (OR, 1.58; 95%CI, 1.10-2.26; P = .012 for 5 mm increase) and vessel size (OR, 1.42; 95%, 1.12-1.79; P = .003 for 0.5 mm reduction) were independently associated with recurrent restenosis. Conclusions: In the largest cohort to date of individuals with angiographic surveillance after DCB angioplasty for DES restenosis, we demonstrated that recurrent restenosis occurs in approximately 1 out of 5 patients. Predictors of recurrent restenosis are increased lesion length and small vessel size

Neuropatía periférica producida por taxanos y calidad de vida global en pacientes con cáncer de mama / Peripheral neuropathy caused by taxanes and overall quality of life in breast cancer patients

OBJETIVO: determinar la incidencia y evolución de la neuropatía periférica inducida por taxanos (NPIT) en pacientes con cáncer de mama y valorar la influencia de la NPIT en la calidad de vida global (CV). MÉTODO: estudio descriptivo longitudinal prospectivo realizado en el Servicio de Oncología del Hospital Clínic de Barcelona (julio 2015-abril 2016). Se incluyeron mujeres diagnosticadas de cáncer de mama en su primera línea de tratamiento con quimioterapia (paclitaxel o docetaxel) en quienes se evaluó la neurotoxicidad y la calidad de vida mediante tres cuestionarios autoinformados validados al inicio, a las 6 y 12 semanas y un mes tras finalizar el tratamiento. RESULTADOS: participaron 33 pacientes de las cuales el 84,4% había desarrollado algún grado de NP al final del seguimiento. La neurotoxicidad empeoró de manera estadísticamente significativa con la acumulación de dosis hasta el final del tratamiento y se mantuvo estable un mes tras la última administración (p< 0,001). La neuropatía sensitiva aumentó de manera estadísticamente significativa a lo largo del seguimiento (p< 0,001). La afectación de la sensibilidad motora también, salvo en la última medición (p< 0,005). Se observó una correlación positiva entre la neurotoxicidad y deterioro de la CV (r= 0,609 (p< 0,0001)) CONCLUSIONES: la NPIT es un efecto secundario con una alta incidencia en la población de mujeres con cáncer de mama estudiada y provoca un efecto negativo en la CV percibida de las pacientes. Las enfermeras oncológicas son profesionales clave en la prevención y el manejo de este efecto secundario

OBJECTIVE: to determine the incidence and evolution of taxane-induced peripheral neuropathy (TIPN) in breast cancer patients, and to assess the influence of TIPN on overall quality of life (QoL). METHOD: a prospective longitudinal descriptive study conducted at the Oncology Unit of the Hospital Clínic de Barcelona (July, 2015- April, 2016). The study included women with diagnosis of breast cancer, on their first line of treatment with chemotherapy (paclitaxel or docetaxel); neurotoxicity and quality of life were evaluated through three self-reported questionnaires validated at baseline, at 6 and 12 weeks, and one month after completing treatment. RESULTS: the study included 33 patients; 84.4% of them had developed some degree of PN at the end of follow-up. There was a statistically significant worsening in neurotoxicity with dose accumulation until the end of the treatment, and it remained stable one month after the last administration (p< 0.001). There was a statistically significant increase in sensitive neuropathy throughout follow-up (p< 0.001); also in terms of involvement in motor sensitivity, except in the final measurement (p< 0-005). A positive correlation was observed between neurotoxicity and QoL deterioration (r= 0.609 (p < 0.0001)). CONCLUSIONS: TIPN is a side effect with high incidence among the population studied of women with breast cancer, and it causes a negative impact on patient-perceived QoL. Oncology nurses are the key professionals for the prevention and management of this side effect

Intensity-modulated radiotherapy combined with paclitaxel and platinum treatment regimens in locally advanced esophageal squamous cell carcinoma

Purpose. This study was conducted to investigate the efficacy and toxicity of combination treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy with paclitaxel plus different platinum agents in locally advanced esophageal squamous cell carcinoma (ESCC). Methods. This retrospective study enrolled 242 patients treated with paclitaxel (135 mg/m2) plus platinum regimens. According to the different platinum agents used, patients were classified into: cisplatin 80 mg/m2 (CP), nidaplatinum 80 mg/m2 (NP), lobaplatin 35 mg/m2 (LP), and oxaliplatin 135 mg m2 (OP) groups, and survival and toxicity rates between the four groups were compared. The median overall survival (OS) was 31.1 months. Results. No significant differences were observed among the CP, NP, LP, and OP groups with regard to 3-year survival rates (46.2, 56.4, 45.7, and 29.0%, respectively). A stratified analysis indicated that 3-year survival rates were significantly lower in the OP group. Renal toxicities and gastrointestinal reactions were more frequent in the CP group than in the other three groups. Three-year survival rates were similar among patients receiving 2, 3, or ≥4 cycles of chemotherapy (40.1, 49.5, and 50.8%, respectively). Multivariate analysis indicated that tumor volume and maximum diameter of metastatic lymph nodes might be independent prognostic factors. Conclusion. Paclitaxel plus nidaplatinum or lobaplatin is recommended in locally advanced ESCC due to their satisfying therapeutic effects and less toxicity. Tumor volume and maximum diameter of metastatic lymph nodes are independent prognostic factors in ESCC patients receiving IMRT and concurrent chemotherapy (AU)

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Relevancia de la variante CYP3A4*20 como predictor de neuropatía inducida por paclitaxel en población española / Relevance of the CYP3A4*20 variant as a predictor of paclitaxel-induced neuropathy in the Spanish population

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