RESUMEN
BACKGROUND: Protein arginine methyltransferase 5 (PRMT5) methylates multiple substrates dysregulated in cancer, including spliceosome machinery components. PF-06939999 is a selective small-molecule PRMT5 inhibitor. PATIENTS AND METHODS: This phase I dose-escalation and -expansion trial (NCT03854227) enrolled patients with selected solid tumors. PF-06939999 was administered orally once or twice a day (q.d./b.i.d.) in 28-day cycles. The objectives were to evaluate PF-06939999 safety and tolerability to identify maximum tolerated dose (MTD) and recommended part 2 dose (RP2D), and assess pharmacokinetics (PK), pharmacodynamics [changes in plasma symmetric dimethylarginine (SDMA) levels], and antitumor activities. RESULTS: In part 1 dose escalation, 28 patients received PF-06939999 (0.5 mg q.d. to 6 mg b.i.d.). Four of 24 (17%) patients reported dose-limiting toxicities: thrombocytopenia (n = 2, 6 mg b.i.d.), anemia (n = 1, 8 mg q.d.), and neutropenia (n = 1, 6 mg q.d.). PF-06939999 exposure increased with dose. Steady-state PK was achieved by day 15. Plasma SDMA was reduced at steady state (58%-88%). Modulation of plasma SDMA was dose dependent. No MTD was determined. In part 2 dose expansion, 26 patients received PF-06939999 6 mg q.d. (RP2D). Overall (part 1 + part 2), the most common grade ≥3 treatment-related adverse events included anemia (28%), thrombocytopenia/platelet count decreased (22%), fatigue (6%), and neutropenia (4%). Three patients (6.8%) had confirmed partial response (head and neck squamous cell carcinoma, n = 1; non-small-cell lung cancer, n = 2), and 19 (43.2%) had stable disease. No predictive biomarkers were identified. CONCLUSIONS: PF-06939999 demonstrated a tolerable safety profile and objective clinical responses in a subset of patients, suggesting that PRMT5 is an interesting cancer target with clinical validation. However, no predictive biomarker was identified. The role of PRMT5 in cancer biology is complex and requires further preclinical, mechanistic investigation to identify predictive biomarkers for patient selection.
Asunto(s)
Neoplasias , Proteína-Arginina N-Metiltransferasas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Proteína-Arginina N-Metiltransferasas/genética , Anciano , Adulto , Mutación , Dosis Máxima Tolerada , Factores de Empalme de ARN , Relación Dosis-Respuesta a DrogaRESUMEN
This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Gastrointestinales , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Guías de Práctica Clínica como AsuntoRESUMEN
BACKGROUND: Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously. PATIENTS AND METHODS: Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer. RESULTS: In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR). CONCLUSIONS: SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors.
Asunto(s)
Inmunoconjugados , Neoplasias Pulmonares , Anticuerpos Monoclonales Humanizados , Camptotecina/análogos & derivados , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: This expansion cohort of a multicenter, dose-escalation, phase I study (NCT00557856) evaluated safety, tolerability, antitumor activity, pharmacokinetics, and pharmacodynamic effects of the anti-activin receptor-like kinase-1 (ALK-1) monoclonal antibody PF-03446962 in advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with HCC and disease progression after prior antiangiogenic therapy or intolerance to treatment received PF-03446962 7 mg/kg intravenously biweekly, as recommended in the dose-escalation part of the study. RESULTS: Twenty-four patients received PF-03446962. The most frequent treatment-related adverse events (AEs) were thrombocytopenia (33.3%), asthenia (29.2), and chills (16.7%). Two patients experienced treatment-related telangiectasia, suggesting an in vivo knockout of ALK-1 function through ALK-1 pathway inhibition. Overall, treatment-related grade 3-4 AEs were reported in eight patients (33.3%). Treatment-related grade 3-4 thrombocytopenia was noted in four patients. No complete or partial responses were reported. Twelve (50%) patients achieved stable disease, which lasted ≥12 weeks in seven (29.2%) patients. The median time to progression was 3 months. Biomarker analyses showed higher mean tumor expression of c-tumor mesenchymal-epithelial transition factor and higher mean serum levels of bone morphogenetic protein-9 in patients with disease control (DC) for ≥12 weeks versus patients with disease progression. Conversely, lower mean serum transforming growth factor-ß and vascular endothelial growth factor receptor-3 levels were detected in patients with DC versus patients with progression. CONCLUSIONS: The observed safety, tolerability, pharmacokinetic profile, and clinical activity support further evaluation of PF-03446962 in patients with HCC and other solid malignancies, as single agent or in combination with other antiangiogenic, chemotherapeutic, or immunotherapeutic agents. TRIAL REGISTRATION NUMBER: NCT00557856.
Asunto(s)
Receptores de Activinas Tipo II/inmunología , Anticuerpos Monoclonales/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Receptores de Activinas Tipo II/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales Humanizados , Biomarcadores de Tumor/antagonistas & inhibidores , Biomarcadores de Tumor/inmunología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Esquema de Medicación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
BACKGROUND: Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small-molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcinoma. MATERIALS AND METHODS: Patients with metastatic pancreatic adenocarcinoma were randomized in a 2:1 fashion to gemcitabine 1000 mg/m(2) weekly for 3 weeks of a 4-week cycle plus rigosertib 1800 mg/m(2) via 2-h continuous IV infusions given twice weekly for 3 weeks of a 4-week cycle (RIG + GEM) versus gemcitabine 1000 mg/m(2) weekly for 3 weeks in a 4-week cycle (GEM). RESULTS: A total of 160 patients were enrolled globally and randomly assigned to RIG + GEM (106 patients) or GEM (54). The most common grade 3 or higher adverse events were neutropenia (8% in the RIG + GEM group versus 6% in the GEM group), hyponatremia (17% versus 4%), and anemia (8% versus 4%). The median overall survival was 6.1 months for RIG + GEM versus 6.4 months for GEM [hazard ratio (HR), 1.24; 95% confidence interval (CI) 0.85-1.81]. The median progression-free survival was 3.4 months for both groups (HR = 0.96; 95% CI 0.68-1.36). The partial response rate was 19% versus 13% for RIG + GEM versus GEM, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40 cases). Other mutations detected included TP53 (13 cases) and PIK3CA (1 case). No correlation between mutational status and efficacy was detected. CONCLUSIONS: The combination of RIG + GEM failed to demonstrate an improvement in survival or response compared with GEM in patients with metastatic pancreatic adenocarcinoma. Rigosertib showed a similar safety profile to that seen in previous trials using the IV formulation.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Glicina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Sulfonas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Proteínas de Ciclo Celular/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasa Clase I , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Glicina/efectos adversos , Glicina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas/genética , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas p21(ras)/genética , Sulfonas/efectos adversos , Proteína p53 Supresora de Tumor/genética , Gemcitabina , Quinasa Tipo Polo 1 , Neoplasias PancreáticasRESUMEN
BACKGROUND: Type 1 insulin-like growth factor receptor (IGF-IR) signaling is often dysregulated in cancer. Cixutumumab, a fully human IgG1 monoclonal antibody, blocks IGF-IR and inhibits downstream signaling. The current study determined the recommended dose, safety, and pharmacokinetic (PK) profile of weekly or every-2-week dosing of cixutumumab. PATIENTS AND METHODS: Two open-label, multicenter phase I studies evaluated weekly (3-15 mg/kg) or every-2-weeks (6-15 mg/kg) dosing of cixutumumab in patients with advanced solid tumors. Serial blood samples for PK were collected up to 168-336 h (day 8-15) following the first administration of cixutumumab. Efficacy was evaluated as best overall tumor response. RESULTS: A total of 24 and 16 patients were enrolled in the weekly and every-2-week dosing studies, respectively. Treatment-emergent adverse events (≥10%) included hyperglycemia, fatigue, anemia, nausea, and vomiting. Severe adverse events (AE) were infrequent; one serious AE (grade 3 electrocardiogram QT prolongation) was deemed possibly cixutumumab-related (10 mg/kg every-2-weeks). One death occurred due to disease progression (6 mg/kg weekly cohort). Maximum serum concentrations increased with dose. A maximum tolerated dose was not identified; pre-determined target serum minimum concentrations (60 µg/mL) were achieved with ≥6 mg/kg weekly and ≥10 mg/kg every-2-week dosing. Cixutumumab terminal elimination half-life is approximately a week (individual range, t1/2 = 4.58-9.33 days based upon 10 mg/kg every 2 weeks). Overall, stable disease was achieved in 25% of all patients. CONCLUSIONS: Cixutumumab was associated with favorable safety and PK profiles. A dosing regimen of 10 mg/kg every 2 weeks was recommended for subsequent disease-focused clinical trials.
Asunto(s)
Anticuerpos Monoclonales/farmacocinética , Antineoplásicos/farmacocinética , Neoplasias/tratamiento farmacológico , Receptor IGF Tipo 1/antagonistas & inhibidores , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Área Bajo la Curva , Femenino , Semivida , Humanos , Masculino , Dosis Máxima Tolerada , Tasa de Depuración Metabólica , Persona de Mediana EdadRESUMEN
Laser ablation (LA) is gaining large acceptance in the treatment of tumor. One of the main risks of this treatment is damaging the healthy tissue around the tumor. Among the solutions proposed to improve the selectivity of the LA and to localize heating to tumor tissue, the use of gold nanoparticles is one of the most promising. The aim of this work is threefold: i) to measure the temperature increase within the tumor during plasmonic photothermal therapy using gold nanorods; ii) to investigate the influence of nanorods concentration and laser settings on both the intra-tumoral temperature and the tumor surface temperature; iii) and to establish the nanorods concentrations able to cause tumor resorption at a defined laser settings. Two sets of trials were performed: i) 16 mice were divided in four groups with different treatment time (i.e., 5 min, 2 min, 1 min, and 30s), with constant gold nanorods amount (i.e., 12.5 µg) and laser power (i.e., 3 W·cm(-2)); ii) 16 mice were divided in four groups treated with different amount of gold nanorods (i.e., control, 12.5 µg, 25 µg, 50 µg) for 5 min at 2 W·cm(-2). Results show significant differences between internal and surface temperatures. We also demonstrate that this temperature difference increases with nanoparticle concentrations, decreases with laser power, and is not influenced by treatment time. This information is critical to improve the theoretical models that will guide future study designs in sensitive orthotopic tumor models.
Asunto(s)
Oro/química , Hipertermia Inducida , Nanotubos/química , Neoplasias/radioterapia , Animales , Línea Celular Tumoral , Humanos , Terapia por Láser , Ratones , Ratones Desnudos , Temperatura , Trasplante HeterólogoRESUMEN
PURPOSE: A first-in-human clinical trial of a fully human, Fc-engineered IgG1 monoclonal antibody targeting integrin α5ß1 was conducted to evaluate tolerability, maximum tolerated dose, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity. METHODS: Escalating doses of PF-04605412 were given IV on day 1, 28 and every 2 weeks thereafter to patients with advanced solid tumors until disease progression or unacceptable toxicity. Sequential dose cohorts were evaluated based on a modified 3 + 3 dose-escalation design. The starting dose was 7.5 mg based on preclinical data. RESULTS: Thirty-three patients were enrolled to six dose levels (7.5, 11.25, 16.9, 34, 68 and 136 mg). Twenty-three patients were evaluable for the primary endpoint (determination of the maximum tolerated dose). Five patients required permanent drug discontinuation due to acute infusion-related reactions, which occurred as grade 3 events in two patients. PK analysis indicated that the targeted drug exposure based on preclinical models was not achieved by the tolerated doses and PK modeling suggesting that doses at least fivefold higher would be necessary. No anti-tumor activity was observed. CONCLUSION: Based on the safety data, the risks associated with the likelihood of significant cytokine-mediated infusion reactions at higher doses, the projected high dose necessary to affect on the biological target and the lack of anti-tumor activity at the doses explored, the trial was prematurely terminated without determining a formal maximum tolerated dose. Further clinical development of PF-04605412 has been discontinued.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Integrina alfa5beta1/inmunología , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/farmacocinética , Área Bajo la Curva , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Fatiga/inducido químicamente , Femenino , Rubor/inducido químicamente , Humanos , Hipotensión/inducido químicamente , Infusiones Intravenosas , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Náusea/inducido químicamente , Neoplasias/metabolismo , Neoplasias/patología , Resultado del TratamientoRESUMEN
AIM: This was a retrospective cohort study of type 2 diabetes patients, to evaluate the association between initial metformin or sulphonylurea treatment and cancer incidence. METHODS: Patients identified in the UK Clinical Practice Research Datalink (CPRD), previously General Practice Research Database, during 1995-2008 who were initially stabilized on OHA monotherapy, including metformin, sulphonylurea, thiazolidinediones (TZDs) or meglitinides, were included in the cohort. New diagnoses of cancer, including malignant solid tumours and haematological malignancies, occurring during the follow-up were identified from the cohort. Age-standardized incidence rates were estimated and compared between metformin and sulphonylurea exposure groups. RESULTS: The age standardized incidences of cancer were 7.5 and 8.5 per 1000 person-years for the metformin and sulphonylurea exposure groups, respectively. After adjusting for potential confounders, the hazard ratios (HR) for malignant solid tumours and haematological malignancies were 1.06 (95% CI: 0.98, 1.15) and 0.98 (95% CI: 0.67, 1.43) for sulphonylurea group as compared to the metformin group, respectively. For individual cancers, the HRs were 1.17 (95% CI: 0.95, 1.44), 1.04 (95% CI: 0.83, 1.31) and 0.88 (95% CI: 0.71, 1.11) for colorectal cancer, breast cancer and prostate cancer, respectively. CONCLUSION: This study provides evidence that cancer incidence in the first few years after starting metformin or sulphonylurea therapy in type 2 diabetes patients is not much affected by choice of hypoglycaemic drug class.
Asunto(s)
Benzamidas/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Metformina/efectos adversos , Neoplasias/epidemiología , Compuestos de Sulfonilurea/efectos adversos , Tiazolidinedionas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Benzamidas/administración & dosificación , Neoplasias de la Mama/epidemiología , Estudios de Cohortes , Neoplasias Colorrectales/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Quimioterapia Combinada , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Incidencia , Masculino , Metformina/administración & dosificación , Persona de Mediana Edad , Neoplasias/etiología , Neoplasias de la Próstata/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Compuestos de Sulfonilurea/administración & dosificación , Tiazolidinedionas/administración & dosificación , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Photodynamic therapy (PDT) has been shown to be effective in the treatment of malignancies of a variety of organ systems, including the lungs, bladder, gastrointestinal tract and skin. Cutaneous lesions serve as ideal targets of PDT because of the accessibility of the skin to light. To achieve optimum results, the photosensitizer must be delivered effectively into the target layers of the skin within a practical timeframe, via noninvasive methods. AIM: To determine whether topical application of a second-generation photosensitizer, silicon phthalocyanine (Pc) 4 [SiPc(OSi(CH3)2 (CH2)3 N(CH3)2)(OH)], results in effective penetration of the skin barrier. METHODS: Penetration of Pc 4 was evaluated using standard Franz-type vertical diffusion cell experiments on surrogate materials (silicone membranes) and laser-scanning confocal microscopy of normal skin biopsy samples from human volunteers. RESULTS: The Franz diffusion data indicate that Pc 4 formulated in an ethanol/propylene glycol solution (70/30%, v/v) can penetrate the membrane at a flux that is appreciable and relatively invariant. Using the same formulation, Pc 4 uptake could be detected in human skin via laser-scanning confocal microscopy. CONCLUSION: After topical application, Pc 4 is absorbed into the epidermis in as little as 1 h, and the absorption increased with increasing time and dose. Pc 4 can be effectively delivered into human skin via topical application. The data also suggest that the degree of penetration is time- and dose-dependent.
Asunto(s)
Indoles/farmacocinética , Compuestos de Organosilicio/farmacocinética , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacocinética , Piel/metabolismo , Administración Tópica , Adulto , Cámaras de Difusión de Cultivos , Femenino , Humanos , Masculino , Membranas Artificiales , Microscopía Confocal , Adulto JovenRESUMEN
BACKGROUND: Pancreatic cancer has proven extremely challenging to treat. A collaborative effort is needed to advance research and improve treatment. An expert conference was conducted to elicit perspectives regarding the current treatment and future research of pancreatic cancer. METHODS: The conference comprised an international panel of experts representing five European countries and the United States. RESULTS: Adjuvant radiotherapy is used more frequently in the United States than in Europe. In locally advanced disease, there is now more emphasis on early chemotherapy in both Europe and the United States. In metastatic disease, combination chemotherapy is commonly used in Europe and the United States. This varies by country. Advancing pancreatic research will require improving biorepositories and developing a roadmap to prioritize therapeutic targets in different models. Small randomized phase II trials of both non-selected and enriched patient populations will help identify activity of new agents. Phase III trials should only be initiated in appropriate patients based on strong clinical and biological signals. Developing drugs in the adjuvant setting may be preferable to eliminate some of the challenges of drug development in the advanced disease setting. CONCLUSION: Progress in research combined with encouraging improvements from the past offer hope for the future of pancreatic cancer patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Investigación Biomédica , Neoplasias Pancreáticas/tratamiento farmacológico , Congresos como Asunto , HumanosRESUMEN
Recent advances in multi-detector computed tomography, magnetic resonance imaging, and ultrasound have led to the detection of incidental ovarian, uterine, vascular and pelvic nodal abnormalities in both the oncology and non-oncology patient population that in the past remained undiscovered. These incidental pelvic lesions have created a management dilemma for both clinicians and radiologists. Depending on the clinical setting, these lesions may require no further evaluation, additional immediate or serial follow-up imaging, or surgical intervention. In this review, guidelines concerning the diagnosis and management of some of the more common pelvic incidentalomas are presented.
Asunto(s)
Neoplasias Pélvicas/diagnóstico , Vasos Sanguíneos/patología , Neoplasias de la Mama/diagnóstico , Femenino , Humanos , Hallazgos Incidentales , Ganglios Linfáticos/patología , Neoplasias Ováricas/diagnóstico , Neoplasias Pélvicas/terapia , Neoplasias Uterinas/diagnósticoRESUMEN
The article summarizes the expert discussion and recommendations on the use of molecular markers and of biological targeted therapies in metastatic colorectal cancer (mCRC), as well as a proposed treatment decision strategy for mCRC treatment. The meeting was conducted during the 11th ESMO/World Gastrointestinal Cancer Congress (WGICC) in Barcelona in June 2009. The manuscript describes the outcome of an expert discussion leading to an expert recommendation. The increasing knowledge on clinical and molecular markers and the availability of biological targeted therapies have major implications in the optimal management in mCRC.
Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Antineoplásicos/efectos adversos , Biomarcadores/metabolismo , Antígeno Carcinoembrionario/análisis , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Receptores ErbB/antagonistas & inhibidores , Humanos , Inestabilidad de Microsatélites , Mutación , Metástasis de la Neoplasia , Pronóstico , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras) , España , Proteínas ras/genéticaRESUMEN
BACKGROUND: Cancer patients often develop the potentially debilitating condition of anaemia. Numerous controlled studies indicate that erythropoiesis-stimulating agents (ESAs) can raise haemoglobin levels and reduce transfusion requirements in anaemic cancer patients receiving chemotherapy. To evaluate recent safety concerns regarding ESAs, we carried out a meta-analysis of controlled ESA oncology trials to examine whether ESA use affects survival, disease progression and risk of venous-thromboembolic events. METHODS: This meta-analysis included studies from the 2006 Cochrane meta-analysis, studies published/updated since the 2006 Cochrane report, and unpublished trial data from Amgen and Centocor Ortho Biotech. The 60 studies analysed (15 323 patients) were conducted in the settings of chemotherapy/radiochemotherapy, radiotherapy only treatment or anaemia of cancer. Data were summarised using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Results indicated that ESA use did not significantly affect mortality (60 studies: OR=1.06; 95% CI: 0.97-1.15) or disease progression (26 studies: OR=1.01; 95% CI: 0.90-1.14), but increased the risk for venous-thromoboembolic events (44 studies: OR=1.48; 95% CI: 1.28-1.72). CONCLUSION: Though this meta-analysis showed no significant effect of ESAs on survival or disease progression, prospectively designed, future randomised clinical trials will further examine the safety and efficacy of ESAs when used according to the revised labelling information.
Asunto(s)
Anemia/tratamiento farmacológico , Hematínicos/uso terapéutico , Neoplasias/mortalidad , Anemia/etiología , Humanos , Neoplasias/complicaciones , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
This article summarizes the expert discussion on the management of hepatocellular carcinoma (HCC), which took place during the 10th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, June 2008. A multidisciplinary approach to a patient with HCC is essential, to guarantee optimal diagnosis and staging, planning of surgical options and selection of embolisation strategies or systemic therapies. In many patients, the underlying cirrhosis represents a challenge and determines therapeutic options. There is now robust evidence in favour of systemic therapy with sorafenib in patients with advanced HCC with preserved liver function. Those involved in the care for patients with HCC should be encouraged to participate in well-designed clinical trials, to increase evidence-based knowledge and to make further progress.
Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , HumanosRESUMEN
OBJECTIVE: To analyze mortality data from patients with Alzheimer's disease (AD), Alzheimer's plus cerebrovascular disease (AD + CVD) or vascular dementia (VaD). METHODS: (1) Meta-analysis of mortality data from double-blind, placebo-controlled, randomized trials; and (2) recontact study to collect additional longer term mortality data from previous galantamine trial participants. RESULTS (META-ANALYSIS): Across 12 trials (< or =6 months duration), there was no increased risk of mortality associated with the use of galantamine (n = 4116) compared with that of placebo (n = 2386) (OR galantamine/placebo: 0.67, 95% CI 0.41-1.10). RESULTS (RECONTACT STUDY): Median survival was 79 months for patients with AD (n = 478) and 59 months for patients with AD + CVD (n = 180) or VaD (n = 145). Prolonged galantamine treatment (> vs < or =6 months) was not associated with decreased survival time (75 vs 61 months respectively; P = 0.02). Cox regression analyses were consistent with the Kaplan-Meier analyses. CONCLUSIONS: We found no short-term or longer term evidence of increased risk of mortality associated with the use of galantamine in patients with AD, AD + CVD or VaD.