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Gac. méd. Méx ; 156(4): 276-282, Jul.-Aug. 2020. graf
Article in English | LILACS | ID: biblio-1249911


Abstract Introduction: A drug-eluting coronary stent is being developed at the National Institute of Cardiology of Mexico for the treatment of ischemic heart disease. Objective: To establish the best animal model for the tests, to show the advances in the drug-eluting stent prototype, to assess two drugs’ antiproliferative activity and histological results. Method: Smooth muscle cell culture tests were performed in order to assess sirolimus and paclitaxel antiproliferative properties. The drugs were encapsulated inside the polymeric matrix of the stents. Rabbits and pigs were used as animal models. Results: Sirolimus and paclitaxel showed an inhibitory effect, which was higher for the latter. Infrared spectroscopy and light and optical microscopy showed that the drug/polymer layer properly adhered to the stent. At a four-week follow-up, both animal models showed satisfactory clinical evolution and adequate histological response, although the porcine model was shown to be more suitable for future protocols. Conclusions: Preliminary tests of the drug-eluting stent provided bases for the development of a study protocol with an adequate number of pigs and with clinical angiographic and histopathological three-month follow-up.

Resumen Introducción: En el Instituto Nacional de Cardiología de México se desarrolla una endoprótesis (stent) coronaria liberadora de fármacos para el tratamiento de la cardiopatía isquémica. Objetivo: Establecer el mejor modelo animal para las pruebas, mostrar los avances en el prototipo del stent liberador de fármacos, evaluar la actividad antiproliferativa de dos fármacos y los resultados histológicos. Método: Se realizaron cultivos de células de músculo liso para evaluar las propiedades antiproliferativas de sirolimus y paclitaxel. Los fármacos fueron encapsulados en el interior de la matriz polimérica de los stents. Se emplearon conejos y cerdos como modelos animales. Resultados: Sirolimus y paclitaxel mostraron efecto inhibitorio, mayor en el segundo. La espectroscopia infrarroja y la microscopia óptica y electrónica mostraron que la capa del polímero con el fármaco se adhería adecuadamente al stent. A las cuatro semanas de seguimiento, ambos modelos animales mostraron evolución clínica satisfactoria y adecuada respuesta histológica, si bien el modelo porcino resultó más conveniente para protocolos futuros. Conclusiones: Las pruebas preliminares del stent liberador de fármaco brindó bases para desarrollar el protocolo con un número adecuado en cerdos y con seguimiento clínico angiográfico e histopatológico a tres meses.

Animals , Male , Female , Rabbits , Paclitaxel/administration & dosage , Sirolimus/administration & dosage , Drug-Eluting Stents , Prosthesis Design , Spectrophotometry, Infrared , Swine , Follow-Up Studies , Disease Models, Animal , Microscopy
Braz. j. med. biol. res ; 53(6): e8885, 2020. tab, graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132519


In this study, we aimed to analyze the anti-cancer effects of β-elemene combined with paclitaxel for ovarian cancer. RT-qPCR, MTT assay, western blot, flow cytometry, and immunohistochemistry were used to analyze in vitro and in vivo anti-cancer effects of combined treatment of β-elemene and paclitaxel. The in vitro results showed that β-elemene+paclitaxel treatment markedly inhibited ovarian cancer cell growth, migration, and invasion compared to either paclitaxel or β-elemene treatment alone. Results demonstrated that β-elemene+paclitaxel induced apoptosis of SKOV3 cells, down-regulated anti-apoptotic Bcl-2 and Bcl-xl gene expression and up-regulated pro-apoptotic P53 and Apaf1 gene expression in SKOV3 cells. Administration of β-elemene+paclitaxel arrested SKOV3 cell cycle at S phase and down-regulated CDK1, cyclin-B1, and P27 gene expression and apoptotic-related resistant gene expression of MDR1, LRP, and TS in SKOV3 cells. In vivo experiments showed that treatment with β-elemene+paclitaxel significantly inhibited ovarian tumor growth and prolonged the overall survival of SKOV3-bearing mice. In addition, the treatment inhibited phosphorylated STAT3 and NF-κB expression in vitro and in vivo. Furthermore, it inhibited migration and invasion through down-regulation of the STAT-NF-κB signaling pathway in SKOV3 cells. In conclusion, the data suggested that β-elemene+paclitaxel can inhibit ovarian cancer growth via down-regulation of the STAT3-NF-κB signaling pathway, which may be a potential therapeutic strategy for ovarian cancer therapy.

Animals , Male , Female , Rabbits , Ovarian Neoplasms/drug therapy , Sesquiterpenes/administration & dosage , Cell Movement/drug effects , NF-kappa B/adverse effects , Paclitaxel/administration & dosage , Apoptosis/drug effects , Cell Proliferation/drug effects , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Immunohistochemistry , Transfection , Signal Transduction , Blotting, Western , NF-kappa B/metabolism , Cell Line, Tumor , Real-Time Polymerase Chain Reaction , Mice, Inbred BALB C
Braz. j. med. biol. res ; 51(3): 7090, 2018. tab, graf
Article in English | LILACS | ID: biblio-889042


Particles are usually polydispersed and size is an important feature for lipid-based drug delivery systems in order to optimize cell-particle interactions as to pharmacologic action and toxicity. Lipid nanoparticles (LDE) with composition similar to that of low-density lipoprotein carrying paclitaxel were shown to markedly reduce atherosclerosis lesions induced in rabbits by cholesterol feeding. The aim of this study was to test whether two LDE fractions, one with small (20-60 nm) and the other with large (60-100 nm) particles, had different actions on the atherosclerotic lesions. The two LDE-paclitaxel fractions, prepared by microfluidization, were separated by density gradient ultracentrifugation and injected (4 mg/body weight, intravenously once a week) into two groups of rabbits previously fed cholesterol for 4 weeks. A group of cholesterol-fed animals injected with saline solution was used as control to assess lesion reduction with treatment. After the treatment period, the animals were euthanized for analysis. After treatment, both the small and large nanoparticle preparations of LDE-paclitaxel had equally strong anti-atherosclerosis action. Both reduced lesion extension in the aorta by roughly 50%, decreased the intima width by 75% and the macrophage presence in the intima by 50%. The two preparations also showed similar toxicity profile. In conclusion, within the 20-100 nm range, size is apparently not an important feature regarding the LDE nanoparticle system and perhaps other solid lipid-based systems.

Animals , Male , Rabbits , Paclitaxel/administration & dosage , Atherosclerosis/drug therapy , Tubulin Modulators/administration & dosage , Nanoparticles/administration & dosage , Lipids/administration & dosage , Lipoproteins, LDL/drug effects , Particle Size , Drug Therapy, Combination
Arq. bras. cardiol ; 107(5): 411-419, Nov. 2016. tab, graf
Article in English | LILACS | ID: biblio-827867


Abstract Background: Atrial electromechanical delay (EMD) is used to predict atrial fibrillation, measured by echocardiography. Objectives: The aim of this study was to assess atrial EMD and mechanical function after anthracycline-containing chemotherapy. Methods: Fifty-three patients with breast cancer (48 ± 8 years old) who received 240 mg/m2of Adriamycin, 2400 mg/m2 of cyclophosphamide, and 960 mg/m2 of paclitaxel were included in this retrospective study, as were 42 healthy subjects (47 ± 9 years old). Echocardiographic measurements were performed 11 ± 7 months (median 9 months) after treatment with anthracyclines. Results: Left intra-atrial EMD (11.4 ± 6.0 vs. 8.1 ± 4.9, p=0.008) and inter-atrial EMD (19.7 ± 7.4 vs. 14.7 ± 6.5, p=0.001) were prolonged; LA passive emptying volume and fraction were decreased (p=0.0001 and p=0.0001); LA active emptying volume and fraction were increased (p=0.0001 and p=0.0001); Mitral A velocity (0.8 ± 0.2 vs. 0.6 ± 0.2, p=0.0001) and mitral E-wave deceleration time (201.2 ± 35.6 vs. 163.7 ± 21.8, p=0.0001) were increased; Mitral E/A ratio (1.0 ± 0.3 vs. 1.3 ± 0.3, p=0.0001) and mitral Em (0.09 ± 0.03 vs. 0.11 ± 0.03, p=0.001) were decreased; Mitral Am (0.11 ± 0.02 vs. 0.09 ± 0.02, p=0.0001) and mitral E/Em ratio (8.8 ± 3.2 vs. 7.6 ± 2.6, p=0.017) were increased in the patients. Conclusions: In patients with breast cancer after anthracycline therapy: Left intra-atrial, inter-atrial electromechanical intervals were prolonged. Diastolic function was impaired. Impaired left ventricular relaxation and left atrial electrical conduction could be contributing to the development of atrial arrhythmias.

Resumo Fundamento: Atraso eletromecânico atrial (AEA) é utilizado para prever fibrilação atrial, medido pela ecocardiografia. Objetivos: O propósito deste estudo era verificar o AEA e a função mecânica após quimioterapia com antraciclinas. Métodos: Cinquenta e três pacientes com câncer de mama (48 ± 8 anos) que receberam 240 mg/m2 de adriamicina, 2400 mg/m2 de ciclofosfamida, e 960 mg/m2 de paclitaxel foram incluídas neste estudo retrospectivo, além de 42 indivíduos saudáveis (47 ± 9 anos). Medidas ecocardiográficas foram realizadas por aproximadamente 11 ± 7 meses (média de 9 meses) após tratamento com antraciclinas. Resultados: AEA esquerdo intra-atrial (11,4 ± 6,0 vs. 8,1 ± 4,9, p=0,008) e AEA interarterial (19,7 ± 7,4 vs. 14,7 ± 6,5, p=0,001) foram prolongados; Volume de esvaziamento passivo e fracionamento de AE diminuíram (p=0,0001 e p=0,0001); Volume de esvaziamento ativo e fracionamento de AE (p=0,0001 e p=0,0001); Tempo de aceleração mitral A (0,8 ± 0,2 vs. 0,6 ± 0,2, p=0,0001) e de desaceleração de onda-E mitral (201,2 ± 35,6 vs. 163,7 ± 21,8, p=0,0001) aumentarão; Razão mitral E/A (1,0 ± 0,3 vs. 1,3 ± 0,3, p=0,0001) e mitral Em (0,09 ± 0,03 vs. 0,11 ± 0,03, p=0,001) diminuíram; Razão mitral Am (0,11 ± 0,02 vs. 0,09 ± 0,02, p=0,0001) e mitral E/Em (8,8 ± 3,2 vs. 7,6 ± 2,6, p=0,017) aumentaram nos pacientes. Conclusões: Em pacientes com câncer de mama após terapia com antraciclina: intervalos eletromecânicos intra-atriais esquerdos, intra-atriais foram prolongados. A função diastólica foi prejudicada. O relaxamento ventricular esquerdo foi prejudicado, e a condução elétrica atrial esquerda pode estar contribuindo para o desenvolvimento de arritmias atriais.

Humans , Female , Adult , Middle Aged , Arrhythmias, Cardiac/etiology , Breast Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Ventricular Function, Left/physiology , Anthracyclines/adverse effects , Atrial Fibrillation/etiology , Atrial Fibrillation/physiopathology , Systole , Blood Pressure/physiology , Echocardiography , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Predictive Value of Tests , Retrospective Studies , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Ventricular Dysfunction, Left/physiopathology , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Diastole
Lima; s.n; nov. 2016.
Non-conventional in Spanish | LILACS, BRISA | ID: biblio-848249


INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de eficacia y seguridad del uso de nab-paclitaxel en combinación con gemcitabina para el tratamiento de adenocarcinoma de páncreas metastásico, sin tratamiento sistémico previo para enfermedad metastásica. Aspectos Generales: El páncreas presenta dos tipos de células principales, las exocrinas y las endocrinas. Dichas células forman distintos tipos de tumor, las cuales a su vez tienen distintos factores de riesgo, causas y síntomas. El cáncer de páncreas más común que se produce en las células exocrinas, es el adenocarcinoma. Así, alrededor del 95% de los canceres de células exocrinas son adenocarcinomas. En pacientes con cáncer de páncreas metastásico se ha estimado una proporción de sobrevida a los cinco años del 2%(4). Asimismo, se ha reportado que en el adenocarcinoma de páncreas metastásico, la mediana de sobrevida es de tres a seis meses. Para estos pacientes, la gemcitabina como monoterapia ha sido considerada el tratamiento estándar de primera línea, la cual se encuentra dentro del petitorio farmacológico de EsSalud. Sin embargo, el cáncer de páncreas metastásico es bastante resistente a la quimioterapia. Más aún, alternativas de tratamiento combinado han probado poco o ningún beneficio en sobrevida global a comparación de gemcitabina sola. Por lo tanto, surge la necesidad de evaluar otras alternativas de tratamiento que prueben un mayor beneficio en relación a gemcitabina sola. el presente dictamen preliminar tiene como objetivo evaluar la eficacia y seguridad del uso de nab-paclitaxel en combinación con gemcitabina para el tratamiento de adenocarcinoma de páncreas metastásico, en pacientes sin tratamiento sistémico previo y así poder valorar si la adición de nab-paclitaxel a gemcitabina supone un beneficio adicional al ya obtenido con gemcitabina sola. Tecnologia Sanitaria de Interés: Paclitaxel pertenece a los medicamentos antineoplásicos conocidos como taxanos. Los taxanos son medicamentos que detienen la división celular interfiriendo con los microtúbulos y evitando así el crecimiento celular. METODOLOGIA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de nab-paclitaxel en combinación con gemcitabina para el tratamiento de adenocarcinoma de páncreas metastásico, en pacientes sin tratamiento sistémico previo. Esta búsqueda \r\nse realizó utilizando los meta-buscadores: Translating Research into Practice (TRIPDATABASE) y National Library of Medicine (Pubmed-Medline). Adicionalmente, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), tales como The National Institute for Health and \r\nCare Excellence (NICE), The Agency for Health care Research and Quality (AHRQ), y The Scottish Medicines Consortium (SMC). RESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda bibliográfica y de evidencia científica hasta octubre 2016 para el sustento del uso de nab-paclitaxel en combinación con gemcitabina para el tratamiento de adenocarcinoma de páncreas metastásico, en pacientes que no han \r\nrecibido tratamiento sistémico previo. Se presenta la evidencia disponible según el tipo de publicación priorizada en los criterios de inclusión (i.e., GP, ETS, RS y ECA fase III). CONCLUSIONES: En el presente documento se evaluó la evidencia científica publicada hasta octubre 2016 en relación al uso de nab-paclitaxel en combinación con gemcitabina para el tratamiento de adenocarcinoma de páncreas metastásico en \r\npacientes sin tratamiento sistémico previo. El uso de gemcitabina como terapia de primera línea es considerado el tratamiento estándar para adenocarcinoma de páncreas metastásico, el cual se encuentra en la actualidad dentro del petitorio farmacológico de EsSalud. Sin embargo, este tipo de cáncer es muy agresivo con corta sobrevida y una elevada resistencia a los medicamentos. Por lo tanto, surge la necesidad de evaluar otras alternativas terapéuticas que prueben un mayor beneficio en relación a gemcitabina sola. Nab-paclitaxel es una formulación alternativa a la de paclitaxel convencional, la cual se caracteriza por que el paclitaxel se encuentra en forma de nano partículas unido a la albúmina. Esta unión permite que las partículas de paclitaxel ingresen dentro de las células tumorales sin necesidad de un solvente sintético, pudiendo mejorar así su eficiencia y seguridad. En la actualidad el ensayo de fase III MPACT, en el cual se evaluó la eficacia y seguridad de nab-paclitaxel más gemcitabina, encontró que esta combinación tuvo un incremento modesto de la sobrevida global (menor a 3 meses) con respecto a la gemcitabina sola, pero acompañado de un incremento en la proporción de eventos adversos y discontinuación del tratamiento por toxicidad inaceptable. Debido a la baja ganancia en la sobrevida global, el incremento de los eventos adversos y a que no se reporta desenlaces en la calidad de vida, no se tiene claridad en la relación riesgo/beneficio del uso de nab-paclitaxel más gemcitabina. Adicionalmente, en el Petitorio Farmacológico de EsSalud existen otras alternativas de tratamiento como gemcitabina sola, FOLFIRINOX y capecitabina que también resultan ser opciones de tratamiento consideradas en las GPC internacionales, con igual o mayor nivel y fuerza de recomendación. El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) no aprueba el uso de nab-paclitaxel en combinación con gemcitabina para el tratamiento de adenocarcinoma de páncreas metastásico, en pacientes que no han recibido tratamiento sistémico previo.

Humans , Anti-Retroviral Agents/administration & dosage , Carcinoma, Pancreatic Ductal/drug therapy , Neoplasm Metastasis/drug therapy , Paclitaxel/administration & dosage , Paclitaxel/analogs & derivatives , Cost-Benefit Analysis , Drug Combinations , Treatment Outcome
Yonsei Medical Journal ; : 337-341, 2016.
Article in English | WPRIM | ID: wpr-147357


PURPOSE: This study compared the angiographic outcomes of paclitaxel-coated balloon (PCB) versus plain old balloon angioplasty (POBA) treatment for de novo coronary artery lesions. At present, there is no available data comparing the efficacy of PCB versus POBA for the treatment of de novo coronary lesions. MATERIALS AND METHODS: This multicenter retrospective observational study enrolled patients with de novo coronary lesions with a reference vessel diameter between 2.5 mm and 3.0 mm and lesion length or =50%) in POBA, compared to PCB (30.4%, n=7 vs. 4.1%, n=2, p<0.001). Target vessel revascularization was higher in the POBA group (13.0%, n=3 vs. 0%, p=0.033). CONCLUSION: PCB treatment of de novo coronary lesions showed better 9-month angiographic outcomes than POBA treatment alone.

Aged , Angioplasty, Balloon, Coronary/instrumentation , Coronary Angiography , Coronary Artery Disease/therapy , Coronary Stenosis/therapy , Coronary Vessels/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Paclitaxel/administration & dosage , Retrospective Studies
Yonsei Medical Journal ; : 606-613, 2016.
Article in English | WPRIM | ID: wpr-52540


PURPOSE: The effects on the side-branch (SB) ostium, following paclitaxel-coated balloon (PCB) treatment of de novo coronary lesions of main vessels have not been previously investigated. This study was aimed at evaluating the serial morphological changes of the SB ostium after PCB treatment of de novo coronary lesions of main vessels using optical coherence tomography (OCT). MATERIALS AND METHODS: This prospective, single-center observational study enrolled patients with de novo lesions, which were traversed by at least one SB (≥1.5 mm) and were treated with PCB. The SB ostium was evaluated with serial angiographic and OCT assessments pre- and post-procedure, and at 9-months follow-up. RESULTS: Sixteen main vessel lesions were successfully treated with PCB, and 26 SBs were included for analysis. Mean SB ostial lumen area increased at 9-months follow-up (0.92±0.68 mm2 pre-procedure, 1.03±0.77 mm2 post-procedure and 1.42±1.18 mm2 at 9-months). The SB ostial lumen area gain was 0.02±0.24 mm2 between pre- and post-procedure, 0.37±0.64 mm2 between post-procedure and 9-months, and 0.60±0.93 mm2 between pre-procedure and 9-months. The ostial lumen area increased by 3.9% [interquartile range (IQR) of -33.3 to 10.4%] between pre- and post-procedure, 52.1% (IQR of -0.7 to 77.3%) between post-procedure and 9-months and 76.1% (IQR of 18.2 to 86.6%) between pre-procedure and 9-months. CONCLUSION: PCB treatment of de novo coronary lesions of main vessels resulted in an increase in the SB ostial lumen area at 9-months.

Aged , Angioplasty, Balloon, Coronary/methods , Coronary Angiography , Coronary Stenosis/diagnosis , Coronary Vessels/pathology , Drug-Eluting Stents/adverse effects , Female , Humans , Male , Middle Aged , Paclitaxel/administration & dosage , Prospective Studies , Tomography, Optical Coherence/methods , Treatment Outcome , Tubulin Modulators/administration & dosage
Arq. bras. cardiol ; 104(6): 450-455, 06/2015. tab, graf
Article in English | LILACS | ID: lil-750703


Background: In chronic Chagas disease (ChD), impairment of cardiac autonomic function bears prognostic implications. Phase‑rectification of RR-interval series isolates the sympathetic, acceleration phase (AC) and parasympathetic, deceleration phase (DC) influences on cardiac autonomic modulation. Objective: This study investigated heart rate variability (HRV) as a function of RR-interval to assess autonomic function in healthy and ChD subjects. Methods: Control (n = 20) and ChD (n = 20) groups were studied. All underwent 60-min head-up tilt table test under ECG recording. Histogram of RR-interval series was calculated, with 100 ms class, ranging from 600–1100 ms. In each class, mean RR-intervals (MNN) and root-mean-squared difference (RMSNN) of consecutive normal RR-intervals that suited a particular class were calculated. Average of all RMSNN values in each class was analyzed as function of MNN, in the whole series (RMSNNT), and in AC (RMSNNAC) and DC (RMSNNDC) phases. Slopes of linear regression lines were compared between groups using Student t-test. Correlation coefficients were tested before comparisons. RMSNN was log-transformed. (α < 0.05). Results: Correlation coefficient was significant in all regressions (p < 0.05). In the control group, RMSNNT, RMSNNAC, and RMSNNDC significantly increased linearly with MNN (p < 0.05). In ChD, only RMSNNAC showed significant increase as a function of MNN, whereas RMSNNT and RMSNNDC did not. Conclusion: HRV increases in proportion with the RR-interval in healthy subjects. This behavior is lost in ChD, particularly in the DC phase, indicating cardiac vagal incompetence. .

Fundamento: Na doença de Chagas (DCh) crônica, a função autonômica cardíaca está frequentemente comprometida e traz implicações quanto ao prognóstico. A retificação de fase da série de intervalos RR isola as influências simpática (fase de aceleração – AC) e parassimpática (fase de desaceleração – DC) na modulação autonômica cardíaca. Objetivo: Este estudo investigou a variabilidade da frequência cardíaca (VRR) como função dos intervalos RR, para avaliar a função autonômica em indivíduos saudáveis e com DCh. Métodos: Os grupos controle (n = 20) e com DCh (n = 20) foram estudados. Todos fizeram o teste de inclinação ortostática de 60 minutos, com o registro do ECG. O histograma da série de intervalos RR dividido em classes de 100 ms, variando de 600 a 1100 ms foi calculado. Para cada classe, foram calculados os intervalos RR médios (MNN) e a diferença média quadrática (RMS) entre os intervalos RR normais que se encaixavam naquela classe. A média de todos os valores de RMS foi analisada como uma função dos MNN na série inteira (RMST) e nas fases de aceleração (RMSAC) e desaceleração (RMSDC). A inclinação das linhas de regressão linear foi comparada entre grupos através do teste t de Student. Os coeficientes de correlação foram testados antes das comparações. A RMS sofreu transformação logarítmica (α < 0,05). Resultados: O coeficiente de correlação foi significativo em todas as regressões (p < 0,05). No grupo controle, a RMST, a RMSAC e a RMSDC aumentaram de forma significativa proporcionalmente ao MNN (p < 0,05). No grupo com DCh, apenas a RMSAC mostrou um aumento significativo como função do MNN, enquanto a RMST e a RMSDC não aumentaram significativamente. Conclusão: A VRR aumenta proporcionalmente ao intervalo RR em indivíduos saudáveis. Este comportamento é perdido na DCh, especialmente na DC, indicando incompetência vagal cardíaca. .

Adult , Female , Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Granulocyte Colony-Stimulating Factor/administration & dosage , Paclitaxel/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Chemotherapy, Adjuvant/methods , Disease-Free Survival , Follow-Up Studies , Lymphatic Metastasis , Pilot Projects , Recombinant Proteins
Rev. méd. Chile ; 143(1): 14-21, ene. 2015. ilus, tab
Article in Spanish | LILACS | ID: lil-742546


Background: Domperidone is widely prescribed in patients with gastrointestinal disorders but some cardiac adverse effects have been recently reported. Aim: To evaluate the risk of QT prolongation, ventricular arrhythmias and sudden cardiac death associated with the use of oral domperidone in adults without cancer. Material and Methods: Systematic searches in MEDLINE, LILACS, SciELO, the Cochrane Library and regulatory agencies websites were performed, followed by a manual search of cited references. The search strategy consisted of combining free and indexed text words without any date or language restriction. Results: Three case-control studies met the inclusion criteria; none of them evaluated QT interval prolongation. With low risk of bias, each study quantified the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD). The odds ratios for these events in these studies were 4.7 (95% confidence interval (CI): 1.4-16), 1.59 (95% CI: 1.28-1.98) and 11.02 (95% CI: 2.02-62.3) respectively. A significantly increased risk was observed in patients older than 60 years of age or receiving doses > 30 mg/day. Conclusions: Heterogeneity between selected studies did not allow the computation of a summary measure. However, evidence was found that an increased risk of VA/SCD is associated with the use of oral domperidone in adults.

Animals , Female , Humans , Mice , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Diterpenes/administration & dosage , Epoxy Compounds/administration & dosage , Paclitaxel/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/chemistry , Apoptosis/drug effects , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Drug Synergism , Diterpenes/chemistry , Epoxy Compounds/chemistry , Lactones/administration & dosage , Lactones/chemistry , Mice, Nude , Oxidative Stress/drug effects , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Tumor Burden , Transcriptional Activation/drug effects , Xenograft Model Antitumor Assays
Article in English | WPRIM | ID: wpr-27941


OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC. METHODS: This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51+/-9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease. RESULTS: Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73+/-5.51 days and the mean hospitalization time was 24.0+/-10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months. CONCLUSION: CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.

Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cisplatin/administration & dosage , Combined Modality Therapy , Cytoreduction Surgical Procedures/adverse effects , Feasibility Studies , Female , Humans , Hyperthermia, Induced/adverse effects , Infusions, Parenteral , Kaplan-Meier Estimate , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Paclitaxel/administration & dosage , Prospective Studies , Treatment Outcome
Article in English | WPRIM | ID: wpr-34113


OBJECTIVE: To evaluate the efficacy and tolerability of a neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy in patients with locally advanced cervical carcinoma. METHODS: Patients with histologically confirmed locally advanced cervical carcinoma, aged > or =18 years, were treated with intravenous ifosfamide 5,000 mg/m2 and mesna 5,000 mg/m2, on day 1; intravenous paclitaxel 175 mg/m2 and cisplatin 75 mg/m2, on day 2; every 3 weeks for three cycles. Following chemotherapy, operable patients underwent radical hysterectomy and pelvic lymphadenectomy, and, if necessary, adjuvant radiotherapy. RESULTS: One hundred fifty-two patients with median age 53 years (range, 24 to 79 years), FIGO stage IIB in 126 (89%), were treated with chemotherapy for median 3 cycles (range, 1 to 3). Treatment was delayed or withdrawn in 23 patients (15%). One hundred thirty-nine patients (91%) underwent surgery. Postchemotherapy pathological complete response rate was 18% (25 patients). Postoperative radiotherapy was administered in 100 patients (72%). The 5-year overall survival and progression-free survival were 87.3% (95% confidence interval [CI], 84.5 to 90.3) and 76.4% (95% CI, 73.5 to 79.5), respectively. CONCLUSION: Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy was feasible and effective in the treatment of locally advanced cervical carcinoma patients with older age and more advanced disease stage than reported in previous studies. Hematological and renal toxicity could be carefully prevented.

Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Cisplatin/administration & dosage , Disease Progression , Feasibility Studies , Female , Humans , Ifosfamide/administration & dosage , Middle Aged , Neoadjuvant Therapy , Paclitaxel/administration & dosage , Retrospective Studies , Treatment Outcome , Uterine Cervical Neoplasms/drug therapy , Young Adult
Article in English | WPRIM | ID: wpr-123435


OBJECTIVE: There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT3 receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC. METHODS: We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT3 receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT3 receptor and dexamethasone with/without aprepitant. RESULTS: When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001). CONCLUSION: The addition of aprepitant therapy was more effective than the control therapy of a 5-HT3 receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.

Adult , Aged , Antiemetics/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Cross-Over Studies , Diet , Drug Administration Schedule , Female , Genital Neoplasms, Female/drug therapy , Granisetron/administration & dosage , Humans , Isoquinolines/administration & dosage , Middle Aged , Morpholines/administration & dosage , Nausea/chemically induced , Paclitaxel/administration & dosage , Quinuclidines/administration & dosage , Serotonin 5-HT3 Receptor Antagonists , Vomiting/chemically induced
J. bras. nefrol ; 36(4): 535-541, Oct-Dec/2014. tab
Article in Portuguese | LILACS | ID: lil-731148


A doença renal crônica (DRC) é caracterizada por uma perda progressiva da função renal e suas principais causas são hipertensão arterial (HA) e diabete melito. Entre as causas de HA, podemos destacar a doença renal aterosclerótica (DRA). O desenvolvimento de DRC nos pacientes com DRA parece ser decorrente não apenas do acometimento das artérias renais principais, mas também da microcirculação renal, o que pode justificar o fato de o sucesso do procedimento não garantir uma melhora da evolução da DRC. Até o presente momento, não existe evidência de benefício da angioplastia em relação ao tratamento clínico exclusivo nos pacientes com DRA. O presente trabalho analisa os estudos mais significantes sobre os desfechos renais em pacientes portadores de DRA submetidos à revascularização ou ao tratamento clínico exclusivo.

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and its main causes are hypertension and diabetes mellitus. Among the causes of hypertension is atherosclerotic renal disease (ARD). The development of CKD in patients with ARD appears to be due not only to the involvement of the main renal arteries, but also of the renal microcirculation, which may explain the fact that the success of the procedure does not guarantee an improvement in the progression of CKD. To date there is no evidence of benefit of angioplasty compared to medical treatment alone in patients with ARD. The present paper analyzes the most significant studies on renal outcomes in patients with ARD undergoing revascularization or medical treatment alone.

Animals , Female , Humans , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/drug therapy , Oxidoreductases/antagonists & inhibitors , Paclitaxel/administration & dosage , Pyrimidines/pharmacology , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Dihydrouracil Dehydrogenase (NADP) , Floxuridine/administration & dosage , Floxuridine/pharmacology , Mice, Inbred ICR , Neoplasm Transplantation , Tegafur/administration & dosage , Tegafur/pharmacology , Uracil/administration & dosage , Uracil/pharmacology
Rev. Esc. Enferm. USP ; 48(spe): 39-44, 08/2014. tab
Article in English | LILACS, BDENF | ID: lil-731298


Objective To identify the association between perineal trauma and pain in 473 primiparous women. Method Cross-sectional study in which pain was measured by the numerical pain scale (0 to 10 - 0 being no pain and 10 maximal pain). Results The prevalence and mean intensity of pain were 33.0% and 4.7 points (standard deviation = 2.0) in the numeric scale, respectively. Episiotomy represented the most frequent trauma (46.7%). The occurrence and intensity of the pain were associated with perineal trauma and postpartum time. Having perineal trauma tripled the chance of pain. Each hour elapsed following the birth reduced the chance of pain by 4.8%. Conclusion Primiparous women are subject to a high frequency of perineal trauma, with episiotomy being the most prominent. Perineal pain affects approximately one-third of primiparous women and is associated with the postpartum time and perineal traumas. .

Objetivo Identificar la asociación entre el trauma y el dolor perineal en 473 primíparas. Método Estudio transversal, en el que el dolor se midió por medio de la escala numérica del dolor (0 a 10; 0 = ningún dolor y 10 = dolor máximo). Resultados La prevalencia y el promedio de intensidad del dolor fueron 33,0% y 4,7 (Desviación Estándar = 2,0) puntos en la escala, respectivamente. La episiotomía fue el trauma más frecuente (46,7%). La ocurrencia y la intensidad del dolor se asociaron con el trauma y el tiempo del postparto. Tener trauma perineal triplica la probabilidad de tener dolor. Cada hora transcurrida después del nacimiento reduce la posibilidad de dolor en 4,8%. Conclusión Las primíparas están sujetas a altas tasas de trauma perineal, especialmente episiotomía. El dolor perineal afecta aproximadamente a un tercio de las primíparas y se asocia con el tiempo de postparto y el traumatismo perineal.


Objetivo Identificar a associação entre trauma perineal e dor em 473 primíparas. Método Estudo transversal, no qual dor foi mensurada por meio da escala numérica de dor (0 a 10 – sendo 0 ausência de dor e 10 dor máxima). A prevalência e a média de intensidade de dor foram 33,0% e 4,7 (Desvio Padrão = 2,0) pontos na escala numérica, respectivamente. Resultados A episiotomia foi o trauma mais frequente (46,7%). A ocorrência e a intensidade da dor foram associadas ao trauma perineal e ao tempo de pós-parto. Ter trauma perineal triplicou a chance de dor. Cada hora decorrida depois do parto reduziu a chance de dor em 4,8%. Conclusão As primíparas estão sujeitas a elevada frequência de trauma perineal, sobretudo episiotomia. A dor perineal afeta, aproximadamente, um terço das primíparas e está associada ao tempo de pós-parto e aos traumas locais. .

Female , Humans , Middle Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma, Intraductal, Noninfiltrating/drug therapy , Paclitaxel/administration & dosage , Paclitaxel/analogs & derivatives , Taxoids , Breast Neoplasms/surgery , Carcinoma, Intraductal, Noninfiltrating/surgery , Floxuridine/administration & dosage , Infusions, Intra-Arterial , Medroxyprogesterone Acetate/administration & dosage , Neoadjuvant Therapy
Invest. clín ; 55(1): 55-60, mar. 2014. ilus, tab
Article in Spanish | LILACS | ID: lil-746285


Se presenta el caso de una paciente de 50 años de edad con cáncer de mama tratada con paclitaxel y BIBF 1120 semanal. La paciente desarrolló al final del duodécimo ciclo de quimioterapia una onicólisis distal, con exudado seroso intenso en el hiponiquio, dolor y mal olor en todas las uñas de las manos. Se trató con ácido fusídico tópico y aceponato de metilprednisolona al 1% dos veces al día, con una excelente respuesta desde los tres primeros días de tratamiento. A la semana de iniciar la terapia tópica, se observó una paroniquia bacteriana con la pérdida de la uña del quinto dedo de la mano izquierda, con cultivos positivos para Staphylococcus aureus sensible a meticilina. Hay pocos casos publicados de onicólisis exudativa asociada a quimioterapia. Sin embargo, están especialmente relacionados con paclitaxel. No se observaron recurrencias de las alteraciones ungueales semanas después de culminar la quimioterapia. Los corticoides tópicos y el ácido fusídico podrían ser considerados como una opción terapéutica cuando la onicólisis exudativa relacionada con paclitaxel esté establecida.

A case of a 50 years-old breast cancer patient treated with weekly paclitaxel and BIBF 1120 is reported herein. At the end of the twelfth cycle of chemotherapy, the patient developed distal onycholysis with intense hyponychium serous exudates, pain and malodor in all her fingernails. It was treated with topical fusidic acid and 1% methylprednisolone aceponate two times daily, with an excellent clinical response from the first three days of treatment. Bacterial paronychia with nail plate loss of the fifth left fingernail was observed a week after the topical therapy was started, with positive cultures for Methicillin susceptible Staphylococcus aureus. There are few reported cases of exudative onycholysis associated with chemotherapy. However, these are especially related to paclitaxel. No recurrences of nail disturbances were observed weeks after the end of chemotherapy. Topical corticosteroids and fusidic acid could be considered as a therapeutic option when exudative onycholysis related to paclitaxel is established.

Female , Humans , Middle Aged , Angiogenesis Inhibitors/adverse effects , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Indoles/adverse effects , Onycholysis/chemically induced , Paclitaxel/adverse effects , Paronychia/chemically induced , Staphylococcal Skin Infections/etiology , Angiogenesis Inhibitors/administration & dosage , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/complications , Disease Susceptibility , Fusidic Acid/therapeutic use , Hand , Indoles/administration & dosage , Methylprednisolone/analogs & derivatives , Methylprednisolone/therapeutic use , Onycholysis/complications , Onycholysis/drug therapy , Onycholysis/microbiology , Paclitaxel/administration & dosage , Paronychia/drug therapy , Paronychia/microbiology , Staphylococcal Skin Infections/drug therapy , Staphylococcal Skin Infections/microbiology
Yonsei Medical Journal ; : 1533-1541, 2014.
Article in English | WPRIM | ID: wpr-221609


PURPOSE: The aim of this study was to evaluate the cost-effectiveness of the use of drug-eluting stents (DESs), as compared with bare-metal stents (BMSs) in Korea. MATERIALS AND METHODS: A retrospective cohort study was conducted between January 2000 and December 2007. Subjects were stent-treated for the first time between 2004 and 2005, with four years of follow-up (2004-2007) (n=43674). The incremental cost-effectiveness ratio (ICER) was used to calculate the costs of DESs compared with BMSs among patients with coronary artery disease (CAD). Cost-effectiveness was assessed with effectiveness defined as a reduction in major adverse cardiac events after six months and after one, two, three, and four years. RESULTS: The total costs of a DESs were 674108 Korean won (KRW) higher than that of a BMSs at the end of the follow-up; 13635 thousand KRW per patient treated with DESs and 12960 thousand KRW per patient treated with BMSs. The ICER was 256315 per KRW/death avoided and 293090 per KRW/re-stenting avoided among the CAD patients at the end of the follow-up. CONCLUSION: The ICER for the high-risk patients was lower than that for the low-risk patients. The use of DESs is clinically more useful than the use of BMSs for CAD and myocardial infarction patients, especially for those considered to be high-risk patients in Korea.

Aged , Angioplasty, Balloon, Coronary , Asian Continental Ancestry Group/statistics & numerical data , Coronary Artery Disease/etiology , Cost-Benefit Analysis , Drug-Eluting Stents/economics , Female , Humans , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Myocardial Infarction/therapy , National Health Programs/statistics & numerical data , Paclitaxel/administration & dosage , Republic of Korea/epidemiology , Retrospective Studies , Risk , Sirolimus/administration & dosage , Stents/adverse effects , Treatment Outcome
Einstein (Säo Paulo) ; 11(4): 446-450, out.-dez. 2013. tab
Article in Portuguese | LILACS | ID: lil-699854


OBJETIVO: Avaliar a taxa de resposta patológica completa atingida pelas pacientes com diagnóstico de câncer de mama localmente avançado submetidas à quimioterapia neoadjuvante baseada no esquema doxorrubicina/ciclofosfamida seguido de paclitaxel. MÉTODOS: Coorte retrospectiva de pacientes admitidas no Hospital de Câncer de Barretos com câncer de mama localmente avançado entre 2006 e 2008 submetidas ao protocolo de doxorrubicina/ciclofosfamida seguido de paclitaxel (4 ciclos de doxorrubicina 60mg/m² e ciclofosfamida 600mg/m² a cada 21 dias; 4 ciclos de paclitaxel 175mg/m² a cada 21 dias). As seguintes variáveis foram avaliadas: idade, menopausa, performance status, estadiamento clínico inicial, dados antropométricos, quimioterapia (dose - duração), perfil de toxicidade, estadiamento clínico pós-tratamento, cirurgia, resposta patológica completa, sobrevida livre de doença e características anatomopatológicas (tipo e grau histológico, perfil hormonal e comprometimento linfonodal). A análise estatística foi realizada considerando-se o nível de significância de 5%. RESULTADOS: Das 434 pacientes avaliadas, 136 foram excluídas por erro no estadiamento ou por terem recebido outro tipo de quimioterapia. A mediana de idade foi 50 anos, todas com performance status 0-1. A mediana do tamanho clínico inicial do tumor foi 65mm e a mediana do tamanho clínico final do tumor foi 22mm. Apresentaram resposta patológica completa 51 (17,1%) pacientes. Aquelas que apresentavam perfil hormonal negativo ou que eram triplo-negativas (Her-2 e perfil hormonal negativos) tiveram impacto favorável na resposta patológica completa. CONCLUSÃO: Quimioterapia neoadjuvante com doxorrubicina/ciclofosfamida seguidas de paclitaxel ofereceu taxa de resposta patológica completa na população estudada de acordo com a literatura. Pacientes triplo-negativas tiveram maior chance de atingir essa resposta.

OBJECTIVE: To evaluate the complete pathologic response attained by patients diagnosed with locally advanced breast cancer submitted to neoadjuvant chemotherapy based on the doxorubicin/cyclophosphamide regimen followed by paclitaxel. METHODS: A retrospective cohort of patients with locally advanced breast cancer, admitted to the Hospital de Câncer de Barretos between 2006 and 2008 submitted to the doxorubicin/cyclophosphamide protocol followed by paclitaxel (4 cycles of doxorubicin 60mg/m² and cyclophosphamide 600mg/m² every 21 days; 4 cycles of paclitaxel 175mg/m² every 21 days). The following variables were assessed: age, menopause, performance status, initial clinical staging, anthropometric data, chemotherapy (dose - duration), toxicity profile, post-treatment staging, surgery, pathologic complete response rate, disease-free survival, and pathological characteristics (type and histological degree, hormonal profile and lymph node involvement). Statistical analysis was performed using a 5% level of significance. RESULTS: Of the 434 patients evaluated, 136 were excluded due to error in staging or because they had received another type of chemotherapy. Median age was 50 years, all with performance status 0-1. Median initial clinical size of tumor was 65mm and the median final clinical size of the tumor was 22mm. Fifty-one (17.1%) patients experienced a pathologic complete response. Those with a negative hormonal profile or who were triple-negative (negative Her-2 and hormonal profile) experienced a favorable impact on the pathologic complete response. CONCLUSION: Neoadjuvant chemotherapy with doxorubicin/cyclophosphamide followed by paclitaxel provided a pathologic complete response in the population studied in accordance with that observed in the literature. Triple-negative patients had a greater chance of attaining this response.

Adult , Aged , Female , Humans , Middle Aged , Young Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Cohort Studies , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Neoadjuvant Therapy , Neoplasm Staging , Paclitaxel/administration & dosage , Retrospective Studies , Treatment Outcome
Indian J Cancer ; 2013 Apr-June; 50(2): 128-134
Article in English | IMSEAR | ID: sea-148637


CONTEXT: Advanced esophageal cancer is aggressive with an expected median survival of 6‑7 months. Combination chemotherapy regimens provide effective palliation, but result in substantial toxicity. MATERIALS AND METHODS: Retrospective analysis of prospectively collected data of patients with advanced esophageal cancer, not amenable to definitive intent therapy who were treated with intravenous weekly paclitaxel. RESULTS: Between October 2010 and August 2011, 51 patients were included. Median age was 56 years, with a male: female ratio of 2.9:1. 29% were mid esophageal and 55% were lower third and gastroesophageal junction tumors. 65% of the tumors had squamous histology. Performance status was > 2 in 45%. 61% patients had received prior therapy, either definitive or palliative. 51% patients were platinum‑pre‑treated and 29% had received prior 3 weekly paclitaxel. 76% patients had distant metastases. Median number of cycles of weekly paclitaxel delivered was 11. 71% of patients had improvement in dysphagia, with a median time to symptom improvement of 9 days. In 72% patients, the feeding nasogastric tube could be removed. Overall response rate was 49% (complete remission: 4%, partial remission: 45%, stable disease: 13%). Median progression free survival was 4.7 months (confidence interval [95% CI: 3.7‑5.7 months]) and median overall survival was 7.5 months (95% CI: 3.1‑11.8 months). Histopathology, performance status and pre‑treatment albumin significantly affected survival. The most common grade 3/4 toxicities included hyponatremia (14%), fatigue (16%), diarrhea (12%), anemia (31%), neutropenia (10%) and febrile neutropenia (4%). CONCLUSIONS: Metronomic weekly paclitaxel chemotherapy may provide palliative benefit in advanced unresectable metastatic esophageal cancer with minimal toxicity.

Administration, Metronomic , Adult , Aged , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Cisplatin/administration & dosage , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/pathology , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosage , Paclitaxel/adverse effects
Indian J Cancer ; 2013 Apr-June; 50(2): 122-127
Article in English | IMSEAR | ID: sea-148636


CONTEXT: There are limited effective therapeutic options in the relapsed setting for non-small cell lung cancer (NSCLC) or in the first line for platinum‑ineligible patients. AIM: To evaluate the safety and efficacy of a metronomic schedule of paclitaxel administered weekly in relapsed refractory NSCLC or upfront in patients not eligible for platinum‑based chemotherapy. SETTINGS AND DESIGN: Retrospective analysis of a prospectively collected database from the medical oncology department at Tata Memorial Hospital in Mumbai, India. MATERIALS AND METHODS: Patients with recurrent and treatment-naïve platinum-ineligible advanced NSCLC were treated with weekly paclitaxel at 80 mg/m2 with palliative intent. Restaging scans were obtained every two months. Chemotherapy was continued until progressive disease, intolerable side effects, or decision of the patient. STATISTICAL ANALYSIS USED: SPSS version 16 was used for analysis. Simple percentages were used for descriptive statistics. Progression‑free survival (PFS) was calculated from date of start of paclitaxel till the date of progression, change of therapy due to any reason, or death due to any cause. Overall survival (OS) was calculated from date of start of paclitaxel to death. The Kaplan Meier method was used for estimation of survival. RESULTS: There were 37 patients over eight months. The median age was 59 years, with a male‑to‑female ratio of 5:1. Two patients received paclitaxel in the first line, 18 patients in second line, nine in third line, five in fourth line, and three were in fifth line. 73% patients had received prior platinum and 48.6% patients had Eastern Cooperative Oncology Group performance status (ECOG PS) >2. The median number of weekly cycles delivered was 14. The response rate was 35% [complete remission (CR): 2.7%, partial remission (PR): 32.4%, stable disease (SD): 32.4%, progressive disease (PD): 27%], the median PFS was four months, and the estimated median OS was seven months. Chemotherapy was well tolerated. The most frequent grade 3 toxicities included anemia: 8%, neutropenia: 5.4%, and sensory neuropathy: 8%. There were no grade 4 toxicities and no episodes of febrile neutropenia. CONCLUSIONS: Weekly low‑dose continuous metronomic‑type scheduling of paclitaxel is safe and effective for relapsed refractory NSCLC and in the first line in platinum-ineligible patients.

Administration, Metronomic , Adult , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , India , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Paclitaxel/administration & dosage , Paclitaxel/adverse effects