RESUMEN
Prostate cancer is among the most frequent cancers in men, and despite its high rate of cure, the high number of cases results in an elevated mortality worldwide. Importantly, prostate cancer incidence is dramatically increasing in western societies in the past decades, suggesting that this type of tumor is exquisitely sensitive to lifestyle changes. Prostate cancer frequently exhibits alterations in the PTEN gene (inactivating mutations or gene deletions) or at the protein level (reduced protein expression or altered sub-cellular compartmentalization). The relevance of PTEN in this type of cancer is further supported by the fact that the sole deletion of PTEN in the murine prostate epithelium recapitulates many of the features of the human disease. In order to study the molecular alterations in prostate cancer, we need to overcome the methodological challenges that this tissue imposes. In this review we present protocols and methods, using PTEN as proof of concept, to study different molecular characteristics of prostate cancer.
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Fosfohidrolasa PTEN/análisis , Fosfohidrolasa PTEN/biosíntesis , Neoplasias de la Próstata/metabolismo , Proteínas Supresoras de Tumor/análisis , Proteínas Supresoras de Tumor/biosíntesis , Animales , Humanos , Masculino , Ratones , Mutación/genética , Fosfohidrolasa PTEN/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: Intravenous (IV) iron supplementation is widely used in hemodialysis (HD) patients to treat their periodic losses. However, the ideal dose and frequency is unknown. The goal of the study is to see if a 20 mg dose of iron IV at the end of each session of HD as iron maintenance is better than the iron prior therapy. We analyze the erythropoiesis activity (EA) and functional iron (FI) after four weeks of treatment. METHODS: In 36 patients, we measure reticulocyte count and content of hemoglobin reticulocyte (CHr) as EA and FI markers, respectively, before and after the treatment. Before the study, 23 patients received another different therapy with IV iron as maintenance therapy. RESULTS: Reticulocyte count: 49.7 ± 23.8 × 10(3) before and 47.2 ± 17.2 × 10(3) after the treatment (p= 0.51). The CHr: 34.8 ± 3.7 pg and 34.4 ± 3.5 pg, respectively, (p= 0.35), showing an excellent correlation with the other FI markers (serum iron r = 0.6; p = 0.001; saturation transferrin r = 0.49; p = 0.004); that is not shown with the serum ferritin (r = 0.23; p = 0.192) or the hepcidin levels (r = 0.22; p = 0.251). There was not a correlation between the C-Reactive Protein, reticulocyte count, and CHr. The 13 patients who did not receive the iron prior to the study showed high FI levels, but not an increased of the serum ferritin or the serum hepcidin levels. CONCLUSIONS: The administration of a small quantity of iron at the end of every HD session keeps the EA and the FI levels and allows reducing the iron overload administered and/or decreasing the iron stores markers in some patients.
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Anemia Ferropénica/tratamiento farmacológico , Compuestos Férricos/administración & dosificación , Ácido Glucárico/administración & dosificación , Hematínicos/administración & dosificación , Quimioterapia de Mantención/métodos , Diálisis Renal/efectos adversos , Administración Intravenosa , Anemia Ferropénica/etiología , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Eritropoyesis/efectos de los fármacos , Femenino , Sacarato de Óxido Férrico , Ferritinas/sangre , Hemoglobinas/análisis , Hepcidinas/sangre , Humanos , Fallo Renal Crónico/terapia , Masculino , Recuento de Reticulocitos , Reticulocitos/metabolismo , Transferrina/análisisRESUMEN
INTRODUCTION: Allogenic hematopoietic stem cell transplant (allo-HSCT) is the treatment of choice for several hematological diseases. Although rare, patients could present nephrotic syndrome as a clinical feature of chronic graft-versus-host disease (cGVHD). The objective of our study is to screen patients with allo-HSCT to determine who developed a glomerular pathology in the context of cGVHD. PATIENTS AND METHODS: We studied patients who underwent allo-HSCT treatment in our center between October 1995 and October 2012 and who developed glomerular pathology. cGVHD was defined as a pathology when it appeared after 100 d post-allo-HSCT. RESULTS: Five hundred eighty-three allo-HSCT were performed. The prevalence of cGVHD of the kidney was 1.03%. All patients with cGVHD of the kidney were hosts who received peripheral blood from an identical HLA match donor. GVHD prophylaxis with calcineurin inhibitors plus methotrexate was administered in five cases, and prophylaxis with sirolimus was used in another case. cGVHD of the kidney was seen to appear after the removal of the prophylaxis for GVHD, within 33 ± 11.54 months intervals after allo-HSCT in five patients and in another patient, it appeared despite immunosuppressive therapy being administered. All patients had proteinuria, within 11.82 ± 9.03 g/d ranges. The kidney biopsies revealed membranous glomerulonephritis (four patients), focal segmental glomerulonephritis (one patient) and lupus nephropathy class III (one patient). It seems, immunosuppressive therapy achieved complete remission, within the first year of treatment in four patients. Although in three of them, the proteinuria recurred when we tried to remove the therapy; two patients have recently started treatment, being in partial remission now. CONCLUSIONS: cGVHD of the kidney is a rare complication after allo-HSCT, related with the removal of the immunosuppression. Monitoring proteinuria in these patients may be useful. In our patients, a complete remission was achieved; although the removal of the immunosuppression may lead to the appearance of outbreaks. We must reconsider the treatment of glomerular pathology secondary to cGVHD.
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Enfermedad Injerto contra Huésped/complicaciones , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedades Renales/etiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Humanos , Lactante , Enfermedades Renales/diagnóstico , Enfermedades Renales/tratamiento farmacológico , Glomérulos Renales/patología , Masculino , Persona de Mediana Edad , Proteinuria/diagnóstico , Estudios Retrospectivos , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety. RESULTS: The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n = 239; bevacizumab, n = 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0-53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand-foot syndrome, and neuropathy. CONCLUSION: Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with single-agent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients.
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Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab , Capecitabina , Neoplasias Colorrectales/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Quimioterapia de Inducción , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Oxaloacetatos , Resultado del TratamientoRESUMEN
The prevalence of psychiatric disorders in dialyzed patients is estimated around 5-20% of the cases. This explains the high use of antidepressant drugs in these patients. We present the case of a 68-year-old woman with a history of renal failure, with chronic hemodialysis and a depressive syndrome in treatment with Mirtazapine. In November 2008, the patient received a renal graft. An immunosuppressant treatment was started with Basiliximab, Tacrolimus, Mycophenolate Mofetil, and corticosteroids. The patient did not present renal immediate renal function. Four days after the transplant, the treatment with Mirtazapine was re-applied, with an asymptomatic hypotension after 2 hours, and without surgical complications. Tacrolimus blood levels were higher than 15 ng/ml. In our opinion, hypotension was a consequence of the interaction Mirtazapine-Tacrolimus in a patient without immediate renal function. This situation has not been described in the literature before, and hypotension could have had negative consequences in the evolution of the graft.
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Antidepresivos Tricíclicos/efectos adversos , Hipotensión/inducido químicamente , Inmunosupresores/efectos adversos , Trasplante de Riñón , Mianserina/análogos & derivados , Tacrolimus/efectos adversos , Anciano , Antidepresivos Tricíclicos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Trastorno Depresivo/complicaciones , Trastorno Depresivo/tratamiento farmacológico , Interacciones Farmacológicas , Femenino , Humanos , Hipotensión/fisiopatología , Inmunosupresores/administración & dosificación , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Mianserina/administración & dosificación , Mianserina/efectos adversos , Mirtazapina , Tacrolimus/administración & dosificaciónRESUMEN
BACKGROUND: The European tacrolimus versus ciclosporin A microemulsion (CsA-ME) renal transplantation study showed that tacrolimus was significantly more effective in preventing acute rejection and had a superior cardiovascular risk profile at 6 months. METHODS: The endpoints of this investigator-initiated, observational, 36-month follow-up were acute rejection incidence rates, rates of patient and graft survival and renal function. An additional analysis was performed using the combined endpoints BPAR, graft loss and patient death. Data available from the original ITT population (557 patients; 286 tacrolimus and 271 CsA-ME) were analysed. RESULTS: A total of 231 tacrolimus and 217 CsA-ME patients participated. At 36 months, Kaplan-Meier-estimated BPAR-free survival rates were 78.8% in the tacrolimus group and 60.6% in the CsA-ME group, graft survival rates were 88.0% and 86.9% and patient survival rates were 96.6% and 96.7%, respectively. The estimated combined endpoint-free survival rate was 71.4% with tacrolimus and 55.4% with CsA-ME (P Asunto(s)
Ciclosporina/uso terapéutico
, Rechazo de Injerto/prevención & control
, Inmunosupresores/uso terapéutico
, Trasplante de Riñón
, Tacrolimus/uso terapéutico
, Adulto
, Biopsia
, Ciclosporina/efectos adversos
, Estudios de Seguimiento
, Rechazo de Injerto/patología
, Humanos
, Inmunosupresores/efectos adversos
, Estimación de Kaplan-Meier
, Riñón/patología
, Persona de Mediana Edad
, Tacrolimus/efectos adversos
, Resultado del Tratamiento
RESUMEN
PURPOSE: The epidermal growth factor receptor (EGFR) is abnormally activated in cancer and two classes of anti-EGFR agents, monoclonal antibodies and low-molecular-weight tyrosine kinase inhibitors, have shown antitumor activity in patients. Because these two classes of antireceptor agents target the EGFR at different sites, we decided to explore whether the combined administration of gefitinib, a tyrosine kinase inhibitor, and cetuximab, a monoclonal antibody, had superior antitumor activity than either agent given alone. EXPERIMENTAL DESIGN: We studied the effects of the combination of gefitinib and cetuximab in a panel of human cancer cell lines and in an EGFR-dependent human tumor xenograft model (A431). The effects of these two agents on EGFR signaling, proliferation, apoptosis, and vascularization were evaluated. In addition, we analyzed, with cDNA arrays, changes in gene expression profiles induced by both agents. RESULTS: The combined treatment with gefitinib and cetuximab resulted in a synergistic effect on cell proliferation and in superior inhibition of EGFR-dependent signaling and induction of apoptosis. In a series of in vivo experiments, single-agent gefitinib or cetuximab resulted in transient complete tumor remission only at the highest doses. In contrast, suboptimal doses of gefitinib and cetuximab given together resulted in a complete and permanent regression of large tumors. In the combination-treated tumors, there was a superior inhibition of EGFR, mitogen-activated protein kinase, and Akt phosphorylation, as well as greater inhibition of cell proliferation and vascularization and enhanced apoptosis. Using cDNA arrays, we found 59 genes that were coregulated and 45 genes differentially regulated, including genes related to cell proliferation and differentiation, transcription, DNA synthesis and repair, angiogenesis, signaling molecules, cytoskeleton organization, and tumor invasion and metastasis. CONCLUSIONS: Our findings suggest both shared and complementary mechanisms of action with gefitinib and cetuximab and support combined EGFR targeting as a clinically exploitable strategy.
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Anticuerpos Monoclonales/farmacología , Receptores ErbB/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/farmacología , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cetuximab , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Receptores ErbB/metabolismo , Femenino , Gefitinib , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Antígeno Ki-67/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neoplasias Experimentales/genética , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/prevención & control , Análisis de Secuencia por Matrices de Oligonucleótidos , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Quinazolinas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
INTRODUCTION: Vascular endothelial growth factor (VEGF) is a key regulator in angiogenesis. Preclinical and clinical data support the role of VEGF and angiogenesis in renal cell carcinoma (RCC), melanoma (M), and soft tissue sarcoma (STS). The tyrosine kinase inhibitor SU5416 is a potent inhibitor of the VEGF receptors 1 and 2. EXPERIMENTAL DESIGN: We investigated 145 mg/m(2) SU5416 twice weekly in patients with advanced or metastatic RCC, M, and STS. The primary objectives were efficacy and safety. Disease assessments were performed after 4 and 8 weeks of treatment and every 2 months thereafter. Documented stable disease (SD) lasting for > or =3 months was considered an antitumor response. RESULTS: A group of 29 patients was entered in the RCC trial, 20 patients in the M trial, and 31 patients in the STS trial. Response was observed in 6 (1 minor response and 5 SDs) of 24 evaluable patients (25%) in the RCC group, 6 (1 minor response and 5 SDs) of 26 patients (23%) in the STS group, and none of the patients in the M group. Progression-free survival ranged from 7 to 252 days (median 59 days) in the RCC group, from 7 to 260 days (median 60 days) in the STS group, and from 14 to 139 days (median 41 days) in the M group. Toxicities observed were those reported previously for SU5416. CONCLUSION: SU5416 single agent is well tolerated. The antitumor response was low in patients with RCC and STS, whereas no responses were seen in patients with M.
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Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Indoles/uso terapéutico , Pirroles/uso terapéutico , Adulto , Anciano , Carcinoma de Células Renales/tratamiento farmacológico , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Renales/tratamiento farmacológico , Masculino , Melanoma/tratamiento farmacológico , Persona de Mediana Edad , Neovascularización Patológica , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Sarcoma/tratamiento farmacológico , Sarcoma/metabolismo , Neoplasias Cutáneas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Intestinal iron absorption was evaluated in 40 patients on hemodialysis therapy treated over 4 months with 105 mg/d of oral iron and recombinant human erythropoietin (rHuEPO). The effect of iron stores, erythropoietic activity (EA), and route of rHuEPO administration on absorption was evaluated. Iron was administered after basal determinations had been made and was stopped 15 days before obtaining the final determinations. Intestinal iron absorption was calculated by summing the increase in hemoglobin (Hb) iron (iron used for the synthesis of new Hb) and variations in estimated tissue iron reserves (reserves at the end of the study minus basal reserves). Markers of EA included soluble transferrin receptors (sTfRs) and erythron transferrin uptake (ETU). Iron losses caused by dialysis or normal obligatory iron losses were not measured. Hb levels increased from 8.38 +/- 1.4 to 10.75 +/- 1.5 g/dL (P < 0.05). sTfR levels reached their maximum value at 45 days (3.22 +/- 0.84 mg/mL; P < 0.05), and ETU increased from 40 +/- 26 to 61 +/- 39 micromol/L whole blood/d (P = 0.007). Intestinal iron absorption was 238 mg (interquartile range [Q75 to Q25], 255) at 2 months and 348 mg (Q75 to Q25, 475) at 4 months (P =0.02) and correlated positively with hematocrit at the end of the study (r = 0.826; P = 0.0001). No relationship between iron absorption and basal serum ferritin level or EA markers was observed. Intestinal iron absorption was similar regardless of the route of rHuEPO administration. In conclusion, intestinal iron absorption from medicinal iron covers erythropoietic requirements and allows Hb levels to increase significantly. It is proportional to the degree of efficient erythropoiesis reached and independent of tissue iron stores present before treatment, markers of EA, and rHuEPO administration route.
Asunto(s)
Eritropoyetina/administración & dosificación , Absorción Intestinal , Hierro/administración & dosificación , Hierro/farmacocinética , Diálisis Renal , Administración Oral , Adulto , Anciano , Femenino , Hematócrito , Hemoglobinometría , Humanos , Masculino , Persona de Mediana Edad , Receptores de Transferrina/sangre , Proteínas Recombinantes , Estadísticas no Paramétricas , Transferrina/metabolismoRESUMEN
The authors report 2 cases of patients who underwent cadaveric renal transplantation from the same donor in a multiorgan extraction procedure. Both cases showed, during the first 6 months posttransplantation, a worsening in renal graft function and signs of ischemia in the homolateral lower limb. One of the cases was preceded by pain in the sciatic region. In imaging tests, a pseudoaneurysm was detected in the iliac artery in both patients. Grafts had to be removed, and the iliac arteries were ligated with posterior isolation of Aspergillus spp from the arterial vessels but not from the renal tissue. Besides surgery, medical treatment with liposomal amphotericin B was initiated with a different outcome in each patient: patient A died, whereas patient B recovered. The absence of Aspergillus spp infection in liver and heart recipients ruled out a donor-transmitted infection. The graft placements were carried out in different operating rooms, which rules out contamination during the transplantation process. All of this leads us to conclude that the infection must have occurred during the preservation phase of the kidney.
Asunto(s)
Aneurisma Falso/etiología , Aspergilosis/complicaciones , Aneurisma Ilíaco/etiología , Trasplante de Riñón/efectos adversos , Adulto , Anfotericina B/uso terapéutico , Aneurisma Falso/tratamiento farmacológico , Aneurisma Falso/cirugía , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/cirugía , Aspergilosis/transmisión , Cadáver , Esquema de Medicación , Femenino , Humanos , Aneurisma Ilíaco/tratamiento farmacológico , Aneurisma Ilíaco/cirugía , Arteria Ilíaca/efectos de los fármacos , Arteria Ilíaca/microbiología , Arteria Ilíaca/cirugía , Arteria Ilíaca/trasplante , Riñón/irrigación sanguínea , Riñón/microbiología , Trasplante de Riñón/métodos , Persona de Mediana Edad , Arteria Renal/microbiología , Arteria Renal/patología , Arteria Renal/cirugía , Donantes de TejidosRESUMEN
Lanthanum carbonate is a nonaluminum, noncalcium phosphate-binding agent, which is widely used in patients with end-stage chronic kidney disease. Until now, no significant side-effects have been described for the clinical use of lanthanum carbonate, and there are no available clinical data regarding its tissue stores. Here we report the case of a 59-year-old patient who was admitted with confusional syndrome. The patient received 3750 mg of lanthanum carbonate daily. Examinations were carried out, and the etiology of the encephalopathy of the patient could not be singled out. The lanthanum carbonate levels in serum and cerebrospinal fluid were high, and the syndrome eased after the drug was removed. The results of our study confirm that, in our case, the lanthanum carbonate did cross the blood-brain barrier (BBB). Although lanthanum carbonate seems a safe drug with minimal absorption, this work reveals the problem derived from the increase of serum levels of lanthanum carbonate, and the possibility that it may cross the BBB. Further research is required on the possible pathologies that increase serum levels of lanthanum carbonate, as well as the risks and side-effects derived from its absorption.
RESUMEN
PURPOSE: Healthy elderly patients with metastatic colorectal cancer may benefit from chemotherapy as much as the younger population. This analysis compares the outcomes of first-line oxaliplatin plus fluoropyrimidines in elderly versus young patients. PATIENTS AND METHODS: 348 patients were randomized to capecitabine 1000 mg/(m2 12 h), days 1-14 plus oxaliplatin 130 mg/m2 day 1, every 3 weeks or weekly infusional 5-FU 2250 mg/m2 over 48 h plus bimonthly oxaliplatin 85 mg/m2. We evaluated response rate, time to progression, overall survival and toxicity according to age. RESULTS: ORR for elderly and young patients were 34.9% and 44.7%, respectively (p=0.081). Median TTP did not differ between the two groups: 8.3 months for patients > or =70 years and 9.6 months for those <70 years (p=0.114). Median OS was 16.8 months and 20.5 months for the > or =70 and <70 years groups, respectively (p=0.74). With XELOX, mild paresthesia and an increase in transaminase levels were more frequent for young patients, whereas grade 3/4 diarrhea was higher in those > or =70 years (25% vs. 8%, p=0.005). For FUOX, only paresthesia was significantly lower in patients > or =70 years (53% vs. 71%, p=0.032). CONCLUSION: Elderly patients with MCRC benefit from first-line oxaliplatin-fluoropyrimidine combinations as much as younger patients, without increased toxicity.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Neoplasias Colorrectales/mortalidad , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Fluorouracilo/uso terapéutico , Humanos , Estimación de Kaplan-Meier , Masculino , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , OxaliplatinoRESUMEN
PURPOSE: The aim of this phase III trial was to compare the efficacy and safety of capecitabine plus oxaliplatin (XELOX) versus Spanish-based continuous-infusion high-dose fluorouracil (FU) plus oxaliplatin (FUOX) regimens as first-line therapy for metastatic colorectal cancer (MCRC). PATIENTS AND METHODS: A total of 348 patients were randomly assigned to receive XELOX (oral capecitabine 1,000 mg/m2 bid for 14 days plus oxaliplatin 130 mg/m2 on day 1 every 3 weeks) or FUOX (continuous-infusion FU 2,250 mg/m2 during 48 hours on days 1, 8, 15, 22, 29, and 36 plus oxaliplatin 85 mg/m2 on days 1, 15, and 29 every 6 weeks). RESULTS: There were no significant differences in efficacy between XELOX and FUOX arms, which showed, respectively, median time to tumor progression (TTP; 8.9 v 9.5 months; P = .153); median overall survival (18.1 v 20.8 months; P = .145); and confirmed response rate (RR; 37% v 46%; P = .539). The safety profile of the two regimens was similar, although there were lower rates of grade 3/4 diarrhea (14% v 24%) and grade 1/2 stomatitis (28% v 43%), and higher rates of grade 1/2 hyperbilirubinemia (37% v 21%) and grade 1/2 hand-foot syndrome (14% v 5%) with XELOX versus FUOX, respectively. CONCLUSION: This randomized study shows a similar TTP of XELOX compared with FUOX in the first-line treatment of MCRC, although there was a trend for slightly lower RR and survival. XELOX can be considered as an alternative to FUOX.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Fluorouracilo/administración & dosificación , Compuestos Organoplatinos/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Capecitabina , Desoxicitidina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Oxaliplatino , España , Resultado del TratamientoRESUMEN
BACKGROUND: Comparison studies of calcineurin inhibitors as cornerstone immunosuppressants in renal transplantation have demonstrated that tacrolimus consistently reduces acute rejection rates and, in some studies, also improves long-term renal outcome in comparison to cyclosporin A (CsA). The aim of the present 2 year follow-up of the European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was to investigate long-term clinical outcome in terms of rate of acute rejection, graft and patient survival and graft function. METHODS: The European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was a randomized, comparative 6 month trial of the calcineurin inhibitors tacrolimus and CsA in combination with both azathioprine and steroids. The intent-to-treat population (ITT) consisted of 286 patients in the tacrolimus arm and 271 in the CsA microemulsion (CsA-ME) arm. Whereas whole blood level targets were 10-20 and 5-15 ng/ml for tacrolimus and 100-400 and 100-200 ng/ml for CsA during months 0-3 and 4-6, respectively, during the investigator-driven follow-up after termination of the main study (months 7-24) no specific calcineurin inhibitor target levels were required. Follow-up data were collected at 2 years post-transplantation from 237 (82.9% of the ITT population) patients who received tacrolimus and 222 (81.9% of the ITT population) patients who received CsA-ME. RESULTS: Calculated on ITT populations, mortality (2.0% vs 3.3%; P<0.05 in Kaplan-Meier analysis) was lower, but rate of graft loss (9.3% vs 11.2%; P = 0.12 in Kaplan-Meier analysis) was not significantly different after 2 years with tacrolimus- vs CsA-ME-based immunosuppression. Biopsy-proven acute rejection was significantly lower (19.6%) with tacrolimus than with CsA-ME (37.3%) during months 0-6 (P<0.0001), but was not significantly different during months 7-12 and 13-24 of follow-up (1.7% and 0.8% with tacrolimus and 4.7% and 0.9% with CsA-ME, respectively). A composite endpoint consisting of graft loss, patient death and biopsy-proven acute rejection occurred significantly more frequently in CsA-ME patients than in tacrolimus patients (42.8% vs 25.9%; P<0.001) during 24 months follow-up. Renal function 2 years post-transplant, measured by serum creatinine concentrations, was significantly better in tacrolimus-based compared with CsA-ME-based immunosuppression (136.9 vs 161.6 micromol/l; P<0.01). Cornerstone immunosuppression remained unchanged in 82.5% and 66.2% of patients treated with tacrolimus and CsA-ME, respectively. At 2 years, more patients in the tacrolimus arm were off steroids and received calcineurin inhibitor monotherapy, and fewer tacrolimus patients remained on a triple immunosuppressive regimen. The cardiovascular risk profile was affected favourably in the tacrolimus arm, with lower cholesterol and triglyceride concentrations (despite less use of cholesterol-lowering drugs); no significant difference in requirement for antidiabetic medication was noted. CONCLUSIONS: The 2 year study results confirm that tacrolimus is a highly efficacious cornerstone immunosuppressant in kidney transplantation. Tacrolimus-based immunosuppression may induce long-term benefits with regard to graft function and graft survival. The overall side-effect profile is considered to be favourable.
Asunto(s)
Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Tacrolimus/uso terapéutico , Adolescente , Adulto , Creatinina/sangre , Ciclosporina/administración & dosificación , Ciclosporina/efectos adversos , Emulsiones , Femenino , Estudios de Seguimiento , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/efectos adversos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Tacrolimus/efectos adversosRESUMEN
Pemetrexed disodium (ALIMTa, [pemetrexed], LY231514; Eli Lilly and Company; Indianapolis, IN), a novel antifolate antimetabolite with multiple enzyme targets involved in both pyrimidine and purine synthesis, has entered clinical trials due to its favorable pleclinical profile. Many studies utilizing the drug, as a single or combination agent, are currently ongoing, including Phase III trials in mesothelioma, nonsmall cell lung carcinoma (NSCLC) and pancreatic cancer. Promising feasibility and activity data have been obtained with pemetrexed in combination with platinum compounds and gemcitabine. The supplementation with daily oral folate could reduce the incidence of hematologic toxicities while preserving the antitumor activity of pemetrexed.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Glutamatos/uso terapéutico , Guanina/análogos & derivados , Guanina/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , Antimetabolitos Antineoplásicos/efectos adversos , Ensayos Clínicos como Asunto , Glutamatos/efectos adversos , Guanina/efectos adversos , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pancreáticas/mortalidad , Pemetrexed , Seguridad , Tasa de Supervivencia , Timidilato Sintasa/antagonistas & inhibidores , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
En el artículo se estudia la prevalencia de los síntomas no dolorosos de la dismenorrea primaria y su evolución según la edad de las mujeres estudiadas (una muestra de 1387 mujeres, de entre 13 y 52 años, y de distintos estratos socioculturales, y de ámbitos urbanos y rurales de la Comunidad Autónoma de Madrid), que completaron un gráfico mensual en el que se recogía la aparición y desaparición de la sintomatologlá asociada en función del momento de aparición de la menstruación. Los síntomas más frecuentes fueron: inflamación de mamas, inflamación de vientre, cambios de humor e irritabilidad. Los síntomas aparecen con mayor frecuencia el día antes y el mismo día de comienzo de la menstruación. No existen diferencias significativas entre los distintos grupos de edad en cuanto a la sintomatología más prevalente (AU)
Asunto(s)
Adolescente , Adulto , Femenino , Persona de Mediana Edad , Niño , Humanos , Dismenorrea/epidemiología , España/epidemiología , Factores de Edad , Factores Socioeconómicos , PrevalenciaRESUMEN
La fluoxetina es uno de los fármacos antidepresivos más utilizados actualmente. Entre sus efectos secundarios está la hiperhidrosis. Presentamos los casos de dos pacientes en tratamiento con fluoxetina por parte del Servicio de Psiquiatría de nuestro hospital que acudieron al Servicio de Dermatología por presentar ambos un cuadro de intensa hiperhidrosis localizada, el primero a nivel del cuero cabelludo y el segundo en axilas, palmas y plantas. En ambos casos los síntomas cedieron tras retirar el fármaco. (AU)
Asunto(s)
Adulto , Femenino , Masculino , Humanos , Hiperhidrosis/complicaciones , Hiperhidrosis/diagnóstico , Hiperhidrosis/etiología , Fluoxetina , Fluoxetina/efectos adversos , Cuero Cabelludo/patología , Axila/patología , Mano/patología , Eccema Dishidrótico/complicaciones , Eccema Dishidrótico/diagnóstico , Eccema Dishidrótico/tratamiento farmacológico , Sertralina , Antidepresivos , Antidepresivos/efectos adversos , Antidepresivos/farmacología , Sistema Enzimático del Citocromo P-450 , Trastorno Bipolar/complicaciones , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/tratamiento farmacológico , Sudoración , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/tratamiento farmacológicoRESUMEN
El presente estudio tiene como doble objetivo: (a) determinar si la estructura de los síntomas no dolorosos de la dismenorrea primaria, en la Comunidad Autónoma de Madrid, se corresponde con la utilizada normalmente en los trabajos al uso; y (b) determinar si los síntomas de la dismenorrea varían en función de la edad de las mujeres estudiadas. Los resultados indican que los síntomas, en las muestras estudiadas, no se corresponden plenamente con los tradicionalmente asociados a la dismenorrea, aunque presentan cierta similitud con éstos, tienen un carácter netamente psicofisiológico y se mantienen estables a lo largo del tiempo, no mostrando diferencias notables entre los grupos de edad estudiados (AU)