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Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Sarcoma , Estudios de Seguimiento , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/epidemiología , Neoplasias Gastrointestinales/terapia , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/epidemiología , Tumores del Estroma Gastrointestinal/terapia , Humanos , Sarcoma/terapiaRESUMEN
Come si leggerà nell'Introduzione della sezione propriamente scientifica del Volume, il presente testo nasce dalla volontà e, soprattutto, dall'esigenza culturale di omaggiare il fu Prof. Antonio Fusco. Un debito scientifico ed umano che trova il suo locus naturale in questa prima parte del testo stesso, cui farà poi seguito la parte propriamente scientifica. In siffatta parentesi dovuta per le ragioni appena menzionate, il lettore, l'amico o l'allievo dell'opera del Prof. Fusco potranno trovare un suo sintetico Curriculum Vitae, correlato da una specifica ed accurata prosa, svolta dal già Magnifico Rettore Carlo Cipolli; il quale, oltre che evidenziare, ricordando, i meriti del collega oramai scomparso, aggiunge alsuo scritto un elemento che sarebbe imprescindibile a non trasformare lo stesso in una mera sequenza di parole: l'amicizia e l'affetto per un amico che, oramai, non c'è più. A fine lettura, evidente risuonerà il fatto che la vita di ognuno, se mossa dalla passione per ciò per cui si è predisposti cognitivamente e psicologicamente, può essere ricca di riconoscimenti, riconoscenze e soddisfazioni che, lungi dal divenire un cuscino di allori su cui adagiarsi, per una mente creativa come quella del Prof. Fusco hanno funto solo da motivazioni ad agire instancabilmente guardando sempre al futuro. Il lavoro di una vita che, materialmente, è sancito da un supporto poco più di cm 25x15: una targa. Una materialità evidente che, con grande commozione e riconoscenza, è stata affissa il 25 ottobre 2019 sull'aula fronte l'Aula Magna del Campus "La Folcara", a testimonianza che quello spirito creativo in continua evoluzione non si ferma; non si arresta neppure con la fine biologica di chi lo ha "posseduto". Rimangono le opere ed il pensiero del Prof. Fusco e restano gli affetti. A tal proposito, il lettore troverà una breve e sentita sezione su Testimonianze; coloro i quali hanno avuto modo, nell'arco della vita accademica ed umana, personale, di Fusco di conoscerlo. Ecco, allora, che i ricordi saranno i veri protagonisti di questa parentesi. Dopo di ciò, prima dei contributi prettamente scientifici dei lavori, tenutisi in occasione del Convegno Internazionale Psicologia, Arte, Letteratura. Antiche e Nuove Tendenze, seguiranno i saluti delle autorità che in quei due giorni si sono succedute a rappresentare non solo l'istituzione affiliata, ma anche la relazione di stima e di affetto che le legava al compianto Professore. Si passerà, infine, al volume tradizionalmente inteso.
Asunto(s)
Psicología/historia , Historia del Siglo XXI , Humanos , ItaliaRESUMEN
BACKGROUND: Treatment options for patients with metastatic pancreatic cancer depend on various factors, including performance status, tumor burden and patient preferences. Metastatic pancreatic cancer is incurable and many systemic treatment options have been investigated over the past decades. This analysis of patterns of practice was performed to identify decision criteria and their impact on the choice of first-line management of metastatic pancreatic cancer. MATERIALS AND METHODS: Members of the Swiss Group for Clinical Cancer Research (SAKK) Gastrointestinal Cancer Group were contacted and agreed to participate in this analysis. Decision trees for the first line treatment of metastatic pancreatic cancer from 9 centers in Switzerland were collected and analyzed based on the objective consensus methodology to identify consensus and discrepancies in clinical decision-making. RESULTS: The final treatment algorithms included 3 decision criteria (comorbidities, performance status and age) and 5 treatment options: FOLFIRINOX, FOLFOX, gemcitabine + nab-paclitaxel, gemcitabine mono and best supportive care. CONCLUSION: We identified multiple decision criteria relevant to all participating centers. We found consensus for the treatment of young (age below 65) patients with good performance status with FOLFIRINOX. For patients with increasing age and reducing performance status there was a decreasing trend to use gemcitabine + nab-paclitaxel. Gemcitabine monotherapy was typically offered to patients in the presence of comorbidities. For patients with ECOG 3-4, most of the experts recommended BSC.
Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Toma de Decisiones Clínicas , Neoplasias Pancreáticas/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Humanos , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/patología , Suiza/epidemiología , Neoplasias PancreáticasRESUMEN
An increasing consumer demand for pomegranate has been globally observed, mainly thanks to the scientific evidence related to its functional and health-promoting features. Pomegranate fruits from twenty accessions identified in Southeastern Italy were characterized according to morphological and chemical features. Juices extracted from pomegranate fruits were fermented with selected Lactobacillus plantarum PU1 and the antioxidant activity investigated. Whey was added to juices to promote the microbial growth. Fermentation led to the increase of the radical scavenging activity (up to 40%) and significant inhibition of the linoleic acid peroxidation. The three fermented juices showing the highest antioxidant activity, and the corresponding unfermented controls, were further characterized. In detail, the cytotoxicity and the protective role toward artificially induced oxidative stress were determined on murine fibroblasts Balb 3T3 through the determination of the viability and the intracellular ROS (reactive oxygen species) scavenging activity (RSA). RSA reached values of ca. 70% in fermented juices, being ca. 40% higher than the unfermented and control samples. Phenols compounds of the pomegranate juices obtained from accessions "Bitonto Piscina," "Sanrà nero," and "Wonderful (reference cultivar) were analyzed through ultrahigh pressure liquid chromatography coupled with mass spectrometry, showing that a marked increase (up to 60%) of the ellagitannins derivatives occurred during fermentation. Sensory analysis showed suitability of the fermented juices to be used as beverage and food ingredient.
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Oncología Médica/normas , Participación del Paciente , Sarcoma/terapia , Adulto , Cuidados Posteriores/métodos , Cuidados Posteriores/normas , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Europa (Continente) , Humanos , Incidencia , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/normas , Oncología Médica/métodos , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/normas , Clasificación del Tumor , Estadificación de Neoplasias , Radioterapia Adyuvante/métodos , Radioterapia Adyuvante/normas , Sarcoma/diagnóstico , Sarcoma/epidemiología , Sarcoma/patología , Grupos de Autoayuda/normas , Sociedades Médicas/normas , Procedimientos Quirúrgicos Operativos/métodos , Procedimientos Quirúrgicos Operativos/normas , Tomografía Computarizada por Rayos X/métodos , Tomografía Computarizada por Rayos X/normas , Resultado del TratamientoAsunto(s)
Tumores del Estroma Gastrointestinal/terapia , Oncología Médica/normas , Participación del Paciente , Adulto , Cuidados Posteriores/métodos , Cuidados Posteriores/normas , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/métodos , Quimioterapia Adyuvante/normas , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Procedimientos Quirúrgicos del Sistema Digestivo/normas , Endosonografía , Europa (Continente) , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/epidemiología , Tumores del Estroma Gastrointestinal/patología , Humanos , Biopsia Guiada por Imagen/métodos , Biopsia Guiada por Imagen/normas , Incidencia , Intestinos/diagnóstico por imagen , Intestinos/patología , Intestinos/cirugía , Laparoscopía/métodos , Laparoscopía/normas , Márgenes de Escisión , Oncología Médica/métodos , Estadificación de Neoplasias , Grupos de Autoayuda/normas , Sociedades Médicas/normas , Estómago/diagnóstico por imagen , Estómago/patología , Estómago/cirugía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Background: This open-label, phase III trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma. Patients and methods: Patients were randomly assigned (1 : 1) to two cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary end point was progression-free survival (PFS). Results: In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years [95% confidence interval (CI), 2.0 to not reached] with cetuximab and 2.0 years (95% CI, 1.5-2.8) with control [hazard ratio (HR), 0.79; 95% CI, 0.58-1.07; P = 0.13]. Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2-4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52-1.01; P = 0.055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31-0.90; P = 0.017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64-1.59, P = 0.97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings. Conclusion: Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma. Clinical trial information: NCT01107639.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/terapia , Quimioradioterapia/mortalidad , Neoplasias Esofágicas/terapia , Esofagectomía/mortalidad , Terapia Neoadyuvante/mortalidad , Adenocarcinoma/patología , Anciano , Carcinoma de Células Escamosas/patología , Cetuximab/administración & dosificación , Cisplatino/administración & dosificación , Terapia Combinada , Docetaxel/administración & dosificación , Neoplasias Esofágicas/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Sorafenib (S), a multitargeted tyrosine kinase inhibitor, is the standard of care for first-line systemic treatment of advanced hepatocellular carcinoma (HCC). Everolimus (E) is a potent inhibitor of mTOR, a pathway frequently activated in HCC. Preclinical data suggest that the combination S + E has additive effects compared with single-agent S. PATIENTS AND METHODS: Patients with unresectable or metastatic HCC and Child-Pugh ≤7 liver dysfunction were randomized to receive daily S 800 mg alone or with E 5 mg until progression or unacceptable toxicity. The primary end point was progression-free survival at 12 weeks (PFS12). The secondary end points included response rate, PFS, time to progression (TTP), overall survival (OS), duration of disease stabilization (DDS), safety, and quality-of-life (QoL) assessments. RESULTS: A total of 106 patients were randomized: 46 patients received S and 60 patients received S + E. Ninety-three patients were assessable for the primary end point and 105 patients for the safety analysis. The PFS12 rate was 70% [95% confidence interval (CI) 54-83] and 68% (95% CI 53-81) in patients randomized to S and S + E, respectively. The RECIST (mRECIST) response rate was 0% (23%) in the S arm and 10% (35%) in the S + E arm. Median PFS (6.6 versus 5.7 months), TTP (7.6 versus 6.3 months), DDS (6.7 versus 6.7 months), and OS (10 versus 12 months) were similar in the S and S + E arms, respectively. Grade 3/4 adverse events occurred in 72% and 86% of patients in arm S and arm S + E, respectively. Patients had similar QoL scores over time, except for a greater worsening in physical well-being and mood in the arm S + E. CONCLUSIONS: No evidence was found that S + E improves the efficacy compared with S alone. Combining 5 mg E with full-dose S is feasible, but more toxic than S alone. Further testing of this drug combination in molecularly unselected HCCs appears unwarranted. CLINICALTRIALSGOV: NCT01005199.
Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Everolimus/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/administración & dosificación , SorafenibRESUMEN
The first description of ligand-independent activating mutations in the KIT gene, which encodes the tyrosine-kinase KIT, greatly improved our understanding of gastrointestinal stromal tumour (GIST) biology. The therapeutic success in GIST has made tyrosine kinase inhibitors a "paradigm of targeted therapy". Deciphering resistance mechanisms in GIST has had implications for many other kinase-driven cancers. To exchange current knowledge within the field of GIST, the German GIST Meeting has taken place for now 10 years, traditionally in Göttingen. Subjects discussed include clinical diagnostics, pathology, surgery, and medical therapy. The following presentation gives an overview of the last meeting held in December 2013, including distinctive features in GIST and current data on the different topics.
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Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/terapia , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/terapia , Terapia Molecular Dirigida/métodos , Alemania , Humanos , Sociedades MédicasRESUMEN
BACKGROUND: Tyrosine kinase inhibitors (TKI) improve the outcome of patients with advanced gastrointestinal stromal tumour (GIST), but treatment failure is frequent, and prognosis then bleak. Smaller trials in this setting suggested activity for sorafenib, a multikinase inhibitor of receptor tyrosine kinases and RAF serine/threonine kinases. PATIENTS AND METHODS: We retrospectively evaluated the efficacy of sorafenib, starting dose 400mg twice daily, in a large community-based cohort of 124 patients treated in 12 European and one United States (U.S.) cancer centre. All but one patient had a WHO performance score 0-2. All had failed both imatinib and sunitinib, 68 patients nilotinib and 26 had failed investigational therapy, too. RESULTS: Twelve (10%) patients responded to sorafenib and 70 (57%) patients achieved disease stabilisation. Sorafenib was moderately tolerated, and toxicity reported in 56% of the patients. Rash, hand-foot-syndrome and diarrhea occurred frequently. Sorafenib dosage was reduced in a third of patients, but this did not have an impact on progression-free survival (PFS) (p=0.15). Median PFS was 6.4 months (95% confidence interval [CI], 4.6-8.0 months) and median overall survival (OS) 13.5 months (95% CI, 10.0-21.0 months). Patients with a good performance status and those who responded to sorafenib had a significant better PFS. CONCLUSION: We conclude that sorafenib is active in GIST resistant to imatinib, sunitinib and nilotinib. These results warrant further investigation of sorafenib or similar molecules in GIST.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Gastrointestinales/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Benzamidas , Quimioterapia Adyuvante , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/patología , Humanos , Mesilato de Imatinib , Indoles/administración & dosificación , Indoles/efectos adversos , Masculino , Persona de Mediana Edad , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Pirroles/administración & dosificación , Pirroles/efectos adversos , Estudios Retrospectivos , Terapia Recuperativa , Sorafenib , Sunitinib , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results. PATIENTS AND METHODS: From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out. RESULTS: Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%-100%. CONCLUSIONS: Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of life.
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Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias del Sistema Nervioso Central/terapia , Linfoma/terapia , Metotrexato/administración & dosificación , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Neoplasias del Sistema Nervioso Central/mortalidad , Terapia Combinada , Irradiación Craneana , Femenino , Estudios de Seguimiento , Humanos , Estado de Ejecución de Karnofsky , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , Calidad de Vida , Trasplante AutólogoRESUMEN
Anti-angiogenic therapies have recently enriched the therapeutic armentarium against the most common cancers. Among these, bevacizumab, a monoclonal antibody against vascular endothelial growth factor, is currently used most frequently. While the addition of bevacizumab to chemotherapy improves overall survival in first and second line treatment of metastatic colorectal cancer, its effect in metastatic breast cancer is limited to improvements in tumor response and progression-free-survival. In non-small-cell lung cancer, the positive results of a first American phase III study have not been confirmed by a second European study and are subject to controversies. A summary of the data concerning anti-angiogenic therapies in these three cancers is presented including safety information.
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Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Neoplasias/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Bevacizumab , Humanos , Neoplasias/patologíaRESUMEN
Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide and its incidence has increased over the last years in most developed countries. The majority of HCCs occur in the context of liver cirrhosis. Therefore, patients with cirrhosis and those with hepatitis B virus infection should enter a surveillance program. Detection of a focal liver lesion by ultrasound should be followed by further investigations to confirm the diagnosis and to permit staging. A number of curative and palliative treatment options are available today. The choice of treatment will depend on the tumor stage, liver function and the presence of portal hypertension as well as the general condition of the patient. A multidisciplinary approach is mandatory to offer to each patient the best treatment.
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Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Trasplante de Hígado , Factores de RiesgoAsunto(s)
Antineoplásicos/sangre , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Piperazinas/sangre , Pirimidinas/sangre , Albúminas/metabolismo , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Benzamidas , Relación Dosis-Respuesta a Droga , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/metabolismo , Genotipo , Glicoproteínas/metabolismo , Humanos , Mesilato de Imatinib , Piperazinas/farmacocinética , Piperazinas/uso terapéutico , Pirimidinas/farmacocinética , Pirimidinas/uso terapéutico , Resultado del TratamientoAsunto(s)
Antineoplásicos/uso terapéutico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Sarcoma/tratamiento farmacológico , Neoplasias Uterinas/tratamiento farmacológico , Anciano , Benzamidas , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Mesilato de Imatinib , Inmunohistoquímica , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/efectos de los fármacosRESUMEN
The treatment of some cancer patients has shifted from traditional, non-specific cytotoxic chemotherapy to chronic treatment with molecular targeted therapies. Imatinib mesylate, a selective inhibitor of tyrosine kinases (TKIs) is the most prominent example of this new era and has opened the way to the development of several additional TKIs, including sunitinib, nilotinib, dasatinib, sorafenib and lapatinib, in the treatment of various hematological malignancies and solid tumors. All these agents are characterized by an important inter-individual pharmacokinetic variability, are at risk for drug interactions, and are not devoid of toxicity. Additionally, they are administered for prolonged periods, anticipating the careful monitoring of their plasma exposure via Therapeutic Drug Monitoring (TDM) to be an important component of patients' follow-up. We have developed a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) requiring 100 microL of plasma for the simultaneous determination of the six major TKIs currently in use. Plasma is purified by protein precipitation and the supernatant is diluted in ammonium formate 20 mM (pH 4.0) 1:2. Reverse-phase chromatographic separation of TKIs is obtained using a gradient elution of 20 mM ammonium formate pH 2.2 and acetonitrile containing 1% formic acid, followed by rinsing and re-equilibration to the initial solvent composition up to 20 min. Analyte quantification, using matrix-matched calibration samples, is performed by electro-spray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effects variability (<9.6%), overall process efficiency (87.1-104.2%), as well as TKIs short- and long-term stability in plasma. The method is precise (inter-day CV%: 1.3-9.4%), accurate (-9.2 to +9.9%) and sensitive (lower limits of quantification comprised between 1 and 10 ng/mL). This is the first broad-range LC-MS/MS assay covering the major currently in-use TKIs. It is an improvement over previous methods in terms of convenience (a single extraction procedure for six major TKIs, reducing significantly the analytical time), sensitivity, selectivity and throughput. It may contribute to filling the current knowledge gaps in the pharmacokinetics/pharmacodynamics relationships of the latest TKIs developed after imatinib and better define their therapeutic ranges in different patient populations in order to evaluate whether a systematic TDM-guided dose adjustment of these anticancer drugs could contribute to minimize the risk of major adverse reactions and to increase the probability of efficient, long lasting, therapeutic response.
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Antineoplásicos/uso terapéutico , Cromatografía Liquida/métodos , Monitoreo de Drogas/métodos , Neoplasias/tratamiento farmacológico , Espectrometría de Masas en Tándem/métodos , Antineoplásicos/sangre , Benzamidas , Bencenosulfonatos/sangre , Bencenosulfonatos/uso terapéutico , Dasatinib , Humanos , Mesilato de Imatinib , Indoles/sangre , Indoles/uso terapéutico , Lapatinib , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Piperazinas/sangre , Piperazinas/uso terapéutico , Piridinas/sangre , Piridinas/uso terapéutico , Pirimidinas/sangre , Pirimidinas/uso terapéutico , Pirroles/sangre , Pirroles/uso terapéutico , Quinazolinas/sangre , Quinazolinas/uso terapéutico , Sorafenib , Sunitinib , Tiazoles/sangre , Tiazoles/uso terapéuticoRESUMEN
Patients diagnosed with advanced gastrointestinal stromal tumours (GISTs) who are resistant or intolerant to both imatinib and second-line sunitinib have a poor prognosis and few therapeutic options. We evaluated the efficacy of nilotinib, a novel tyrosine kinase inhibitor (TKI) in patients pretreated with imatinib and sunitinib. Fifty-two consecutive patients treated with oral nilotinib, 400mg twice daily, within the nilotinib compassionate use programme in 12 European cancer centres, were included in this retrospective analysis. Median age was 59 years (range 24-80), and all patients had WHO performance score better than 3. All patients had failed both imatinib and sunitinib pretreatment, either due to progressing GIST (96%) or intolerance (4%). Five patients (10%; 95% confidence interval (CI) 2-18) responded to nilotinib and 19 patients (37%; 95% CI 24-50) achieved a disease stabilisation. Nilotinib was generally well tolerated, but six patients (12%) discontinued treatment due to intolerance. Median progression-free survival of nilotinib treatment was 12 weeks (95% CI 9-15; range 0-104) and median overall survival was 34 weeks (95% CI 3-65; range 2-135). Nilotinib is active in GIST resistant to both imatinib and sunitinib. These results warrant further investigation of nilotinib in GIST.
Asunto(s)
Antineoplásicos/administración & dosificación , Resistencia a Antineoplásicos , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Pirimidinas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Benzamidas , Supervivencia sin Enfermedad , Femenino , Tumores del Estroma Gastrointestinal/mortalidad , Humanos , Mesilato de Imatinib , Indoles/efectos adversos , Masculino , Persona de Mediana Edad , Selección de Paciente , Piperazinas/efectos adversos , Pirimidinas/efectos adversos , Pirroles/efectos adversos , Estudios Retrospectivos , Sunitinib , Resultado del Tratamiento , Adulto JovenRESUMEN
Colorectal cancer is the 2nd cause of cancer related death in industrialised countries. 20% of all patients present with metastatic disease at diagnosis and need systemic treatment. Since the introduction of irinotecan and oxaliplatin as part of standard chemotherapy, and recently the new targeted agents bevacizumab, cetuximab and panitumumab, the overall survival for patients suffering from metastatic colorectal cancer (mCRC) has increased significantly and nearly reaches 2 years nowadays. Surgery or radiofrequency ablation has become central in the care of metastatic disease. This article resumes recent therapeutic advances in the field and emphasizes the multidisciplinary concertation between specialists to obtain the best outcome.