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1.
Nat Med ; 26(5): 665-671, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32405058

RESUMEN

The current COVID-19 pandemic challenges oncologists to profoundly re-organize oncological care in order to dramatically reduce hospital visits and admissions and therapy-induced immune-related complications without compromising cancer outcomes. Since COVID-19 is a novel disease, guidance by scientific evidence is often unavailable, and impactful decisions are inevitably made on the basis of expert opinions. Here we report how the seven comprehensive cancer centers of Cancer Core Europe have organized their healthcare systems at an unprecedented scale and pace to make their operations 'pandemic proof'. We identify and discuss many commonalities, but also important local differences, and pinpoint critical research priorities to enable evidence-based remodeling of cancer care during the COVID-19 pandemic. Also, we discuss how the current situation offers a unique window of opportunity for assessing the effects of de-escalating anticancer regimens, which may fast-forward the development of more-refined and less-toxic treatments. By sharing our joint experiences, we offer a roadmap for proceeding and aim to mobilize the global research community to generate the data that are critically needed to offer the best possible care to patients.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Neoplasias , Neumonía Viral/epidemiología , Atención Ambulatoria/estadística & datos numéricos , COVID-19 , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/prevención & control , Atención a la Salud , Humanos , Neoplasias/complicaciones , Neoplasias/terapia , Pandemias/prevención & control , Neumonía Viral/complicaciones , Neumonía Viral/prevención & control , SARS-CoV-2
2.
Eur J Cancer ; 109: 103-110, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30711772

RESUMEN

BACKGROUND: Bromodomain and extraterminal motif (BET) protein inhibition is a promising cancer treatment strategy, notably for targeting MYC- or BRD4-driven diseases. A first-in-human study investigated the safety, pharmacokinetics, maximum tolerated dose and recommended phase II dose of the BET inhibitor BAY 1238097 in patients with advanced malignancies. MATERIAL AND METHODS: In this phase I, open-label, non-randomised, multicentre study, patients with cytologically or histologically confirmed advanced refractory malignancies received oral BAY 1238097 twice weekly in 21-day cycles using an adaptive dose-escalation design at a starting dose of 10 mg/week. Model-based dose-response analysis was performed to guide dose escalation. Safety, pharmacokinetics, pharmacodynamics and tumour response were evaluated. RESULTS: Eight patients were enrolled at three dose levels (10 mg/week, n = 3; 40 mg/week, n = 3; 80 mg/week, n = 2). Both patients receiving 80 mg/week had dose-limiting toxicities (DLTs) (grade 3 vomiting, grade 3 headache and grade 2/3 back pain). The most common adverse events were nausea, vomiting, headache, back pain and fatigue. Pharmacokinetic analysis indicated a linear dose response with increasing dose. Two patients displayed prolonged stable disease; no responses were observed. Biomarker evaluation of MYC and HEXIM1 expression demonstrated an emerging pharmacokinetic/pharmacodynamic relationship, with a trend towards decreased MYC and increased HEXIM1 expression in response to treatment. CONCLUSION: The study was prematurely terminated because of the occurrence of DLTs at a dose below targeted drug exposure. Pharmacokinetic modelling indicated that an alternate dosing schedule whereby DLTs could be avoided while reaching efficacious exposure was not feasible. Registration number: NCT02369029.


Asunto(s)
Benzodiazepinas/farmacocinética , Benzodiazepinas/uso terapéutico , Proteínas de Ciclo Celular/antagonistas & inhibidores , Resistencia a Antineoplásicos/efectos de los fármacos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Neoplasias/tratamiento farmacológico , Factores de Transcripción/antagonistas & inhibidores , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/patología , Pronóstico , Distribución Tisular
3.
Cancer Biomark ; 17(3): 323-333, 2016 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-27802208

RESUMEN

BACKGROUND: Resectable non-small cell lung cancer (NSCLC) treatment options most often consist of surgical resection along with adjuvant chemotherapy (ACT). The benefit of ACT however is modest and is accompanied by important side effects. OBJECTIVE: One central quest in the field is therefore the identification of a predictive marker of the response to ACT. METHODS: We applied an unbiased approach based on high content analysis of expression data generated from a discovery patient cohort. RESULTS: We identified MMS19, a component of the cytoplasmic Iron-Sulfur Assembly (CIA) machinery important for the Nucleotide Excision Repair (NER) pathway as a pivotal gene for cisplatin toxicity. We then confirmed the association between MMS19 expression and the response to Cisplatin treatment in a panel of NSCLC cell lines. Finally we validated these pre-clinical data in a subgroup of JBR.10 trial patients through a hypothesis-driven analysis, and showed that MMS19 levels associated with ACT benefit. CONCLUSIONS: We therefore propose the expression level of MMS19 as a candidate predictive marker of ACT benefit in resected NSCLC patients.


Asunto(s)
Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Factores de Transcripción/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Quimioterapia Adyuvante , Expresión Génica , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Transcripción/metabolismo , Resultado del Tratamiento
4.
Bull Cancer ; 103(7-8): 667-73, 2016.
Artículo en Francés | MEDLINE | ID: mdl-27417336

RESUMEN

Anthracyclines and molecular targeted agents have improved prognosis of patients undergoing chemotherapeutics for malignancy. However, the use of these therapies is limited because of risk of cardiac toxicity. The severity of the cardiomyopathy can range from an asymptomatic left ventricular (LV) dysfunction to a severe congestive heart failure. Cardiomyopathy can be reversible or irreversible according to the type of chemotherapy, modality of administration and patient's characteristics. Several studies aimed to early detection and the evaluation of tools to characterize patients at risk to develop cardiac side effects in order to prevent severe LV dysfunction. According to this literature, it is recommended that initial assessment and follow-up of patients undergoing these chemotherapies be performed using troponin dosage, assessment of left ventricle ejection fraction and evaluation of LV myocardial deformation assessing LV global longitudinal strain.


Asunto(s)
Antraciclinas/efectos adversos , Cardiopatías/inducido químicamente , Cardiopatías/prevención & control , Humanos , Indoles/efectos adversos , Niacinamida/efectos adversos , Niacinamida/análogos & derivados , Compuestos de Fenilurea/efectos adversos , Pirroles/efectos adversos , Sorafenib , Sunitinib , Trastuzumab/efectos adversos , Troponina/análisis
5.
Eur Urol ; 65(4): 713-20, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23993162

RESUMEN

BACKGROUND: Response Evaluation Criteria in Solid Tumors (RECIST) criteria may not be sufficient to evaluate the response of targeted therapies in metastatic renal cell carcinoma (mRCC). The tumor growth rate (TGR) incorporates the time between evaluations and may be adequate. OBJECTIVE: To determine how TGR is modified along the treatment sequence and is associated with outcome in mRCC patients. DESIGN, SETTING, AND PARTICIPANTS: Medical records from all patients prospectively treated at Gustave Roussy (IGR) in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) (sorafenib vs placebo, n=84) and the RECORD (everolimus vs placebo, n=43) phase 3 trials were analyzed. TGR was computed across clinically relevant periods: BEFORE treatment introduction (wash-out), UNDER (first cycle), at PROGRESSION (last cycle) and AFTER treatment discontinuation (washout). The association between TGR and outcome (overall survival [OS] and progression-free survival [PFS]) was computed in the entire TARGET cohort (n=903). INTERVENTION: Sorafenib, everolimus, or placebo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: TGR, RECIST, OS, and PFS rates. RESULTS AND LIMITATIONS: Although nearly all the patients (IGR) were classified as stable disease (RECIST) after the first cycle, the great majority of the patients exhibited a decrease in TGR UNDER compared with BEFORE (sorafenib: p<0.00001; everolimus: p<0.00001). In sorafenib-treated but not in everolimus-treated patients (IGR), TGR at PROGRESSION (last cycle) was still lower than TGR BEFORE (washout) (p=0.012), while TGR AFTER progression (washout) was higher than TGR at PROGRESSION (last cycle) (p=0.0012). Higher TGR (first cycle) was associated with worse PFS (hazard ratio [HR]: 3.61; 95% confidence interval [CI], 2.45-5.34) and worse OS (HR: 4.69; 95% CI, 1.54-14.39), independently from the Motzer score and from the treatment arm in the entire TARGET cohort. CONCLUSIONS: Computing TGR in mRCC patients is simple and provides clinically useful information for mRCC patients: (1) TGR is independently associated with prognosis (PFS, OS), (2) TGR allows for a subtle and quantitative characterization of drug activity at the first evaluation, and (3) TGR reveals clear drug-specific profiles at progression.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/secundario , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Sirolimus/análogos & derivados , Carcinoma de Células Renales/patología , Supervivencia sin Enfermedad , Everolimus , Humanos , Niacinamida/uso terapéutico , Estudios Prospectivos , Sirolimus/uso terapéutico , Sorafenib , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral
6.
Clin Cancer Res ; 19(5): 1257-68, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-23339124

RESUMEN

PURPOSE: Signaling through the fibroblast growth factor (FGF) pathway may account for tumor resistance to antiangiogenic therapies targeting the VEGF pathway. Here, dovitinib (TKI258), a potent oral inhibitor of FGF receptor, VEGF receptor (VEGFR), and platelet-derived growth factor receptor tyrosine kinases, is studied in a dose escalation trial. EXPERIMENTAL DESIGN: Patients with advanced or metastatic renal cell carcinoma (RCC) with predominant clear cell histology were treated with oral dovitinib 500 or 600 mg/day (5-days-on/2-days-off schedule). RESULTS: Twenty heavily pretreated patients (median 3 prior regimens) were enrolled, with 16, 11, and 12 patients having previously received at least 1: VEGFR inhibitor, mTOR inhibitor, and immunotherapy, respectively. Fifteen and 5 patients were treated in 500- and 600-mg cohorts, respectively. Three patients experienced dose-limiting toxicities: grade 2 bradycardia (500 mg), grade 4 hypertensive crisis (600 mg), and grade 3 asthenia with grade 2 nausea and vomiting (600 mg). The most common adverse events related to dovitinib were nausea (75%), diarrhea (70%), vomiting (70%), and asthenia (50%), the majority of which were mild (grade 1 or 2), with grade 3 events 5% or less (except asthenia, 15%) and only one grade 4 event (hypertensive crisis). Two patients achieved a partial response (500 mg), and 12 patients had stable disease, including 2 patients with long lasting disease stabilizations (>1 year) in the 500-mg cohort. CONCLUSIONS: Dovitinib was tolerable and showed antitumor activity at a maximum tolerated dose of 500 mg on a 5-days-on/2-days-off schedule in heavily pretreated RCC patients.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Bencimidazoles/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Quinolonas/uso terapéutico , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Receptor 1 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Adulto , Anciano , Animales , Protocolos de Quimioterapia Combinada Antineoplásica , Bencimidazoles/farmacocinética , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/secundario , Evaluación Preclínica de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Dosis Máxima Tolerada , Ratones , Ratones Desnudos , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/análogos & derivados , Niacinamida/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinolonas/farmacocinética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Sorafenib , Tasa de Supervivencia , Distribución Tisular , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo
7.
Cell Cycle ; 12(4): 647-54, 2013 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-23343765

RESUMEN

Non-small cell lung carcinoma (NSCLC) is the most common form of lung cancer and is associated with a high mortality rate worldwide. The majority of individuals bearing NSCLC are treated with surgery plus adjuvant cisplatin, an initially effective therapeutic regimen that, however, is unable to prevent relapse within 5 years after tumor resection in an elevated proportion of patients. The factors that predict the clinical course of NSCLC and its sensitivity to therapy remain largely obscure. One notable exception is provided by pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. PDXK has recently been shown to be required for optimal cisplatin responses in vitro and in vivo and to constitute a bona fide prognostic marker in the NSCLC setting. Together with PDXK, 84 additional factors were identified that influence the response of NSCLC cells to cisplatin, in vitro including the hepatic lipase LIPC. Here, we report that the intratumoral levels of LIPC, as assessed by immunohistochemistry in two independent cohorts of NSCLC patients, positively correlate with disease outcome. In one out of two cohorts studied, the overall survival of NSCLC patients bearing LIPChigh lesions was unaffected, if not slightly worsened, by cisplatin-based adjuvant therapy. Conversely, the overall survival of patients with LIPClow lesions was prolonged by post-operative cisplatin. Pending validation in appropriate clinical series, these results suggest that LIPClow NSCLC patients would be those who mainly benefit from adjuvant cisplatin therapy. Thus, the expression levels of LIPC appear to have an independent prognostic value (and perhaps a predictive potential) in the setting of NSCLC. If these findings were confirmed by additional studies, LIPC expression levels might allow not only for NSCLC patient stratification, but also for the implementation of personalized therapeutic approaches.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Lipasa/genética , Neoplasias Pulmonares/genética , Fosfoproteínas Fosfatasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Biomarcadores Farmacológicos/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Estudios de Cohortes , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Lipasa/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fosfoproteínas Fosfatasas/metabolismo , Medicina de Precisión , Valor Predictivo de las Pruebas , Pronóstico , Análisis de Supervivencia
8.
Nat Rev Clin Oncol ; 8(3): 177-83, 2011 03.
Artículo en Inglés | MEDLINE | ID: mdl-21364691

RESUMEN

Three advances are dramatically changing the landscape of oncology. First, hundreds of drugs are available that inhibit targets involved in oncogenesis. Second, efforts to reclassify malignant diseases are expanding the number of orphan molecular diseases. Third, the implementation of high-throughput technologies will allow risk of relapse prediction and drug sensitivity. Patients predicted to relapse will be referred to comprehensive cancer centers where new drugs will be tested. It is anticipated that a high number of small, biology-driven clinical trials will report high sensitivity to targeted agents in rare biologically defined diseases. Drug registration and biomarker analysis needs to be revisited to avoid large phase III trials with control arms. The use of high-throughput technologies will lead to the development of virtual cells. These considerations highlight the need for developing a consortium of comprehensive cancer centers to run clinical trials in rare, molecularly-defined populations, and implement high-throughput technologies for daily practice.


Asunto(s)
Instituciones Oncológicas , Neoplasias/diagnóstico , Neoplasias/terapia , Medicina de Precisión , Humanos
9.
J Thorac Oncol ; 5(3): 369-75, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20090562

RESUMEN

INTRODUCTION: We examined the efficacy of enzastaurin plus pemetrexed as second-line therapy in patients with advanced (stage IIIA/B or IV) non-small cell lung cancer in a double-blinded, randomized, phase II study. METHODS: Patients received pemetrexed 500 mg/m intravenously on day 1 of 21-day cycles (day 8 in cycle 1) plus oral enzastaurin (250 mg two times per day; combination arm) or placebo (pemetrexed arm). Both arms received supplementation with vitamin B12, folic acid, and dexamethasone. An interim analysis was conducted to determine whether efficacy would warrant a phase III study. RESULTS: The interim analysis showed no evidence of improved progression-free survival with enzastaurin. At final analysis (N = 160, 80 in each arm), baseline characteristics were well balanced. There was no significant difference in progression-free survival (3.0 months, p = 0.544) or overall survival (9.6 months in combination arm and 7.4 months in pemetrexed arm, p = 0.171). Drug-related serious adverse events included cerebrovascular accident, palpitations, and renal failure (n = 1, each) in combination arm and neutropenic sepsis, thrombocytopenia, and panniculitis (n = 1, each) in pemetrexed arm. Nonhematologic drug-related grade 3/4 toxicities were similar in both arms. Grade 3/4 hematologic toxicities were higher with the combination, specifically leukopenia (6.3% versus 0%), neutropenia (15.2% versus 5.0%), and thrombocytopenia (8.9% versus 1.3%). Of the 26 deaths reported on-study or within 30 days of discontinuation (10 in combination arm and 16 in pemetrexed arm), none were drug related. CONCLUSION: The combination regimen of enzastaurin and pemetrexed is well tolerated but does not improve efficacy over pemetrexed and placebo as second-line treatment of unselected patients with advanced non-small cell lung cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Método Doble Ciego , Femenino , Ácido Fólico/administración & dosificación , Glutamatos/administración & dosificación , Guanina/administración & dosificación , Guanina/análogos & derivados , Humanos , Indoles/administración & dosificación , Neoplasias Pulmonares/patología , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Estadificación de Neoplasias , Pemetrexed , Pronóstico , Terapia Recuperativa , Tasa de Supervivencia , Vitamina B 12/administración & dosificación
11.
Target Oncol ; 4(2): 89-97, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19418112

RESUMEN

Among toxicities associated with molecular targeted agents (MTA), cardiovascular toxicities remain largely unknown or underestimated. Their frequency is variable and dependent on the compound. A high incidence of hypertension, symptomatic or asymptomatic left ventricular systolic dysfunction, acute coronary syndrome, arterial and venous thrombosis has been observed in patients receiving MTA. One of the most threatening complications of angiogenic inhibitors (AI) could be QT prolongation with the risk of torsade de pointes (TdP) and sudden death. QT prolongation and torsade de pointes accounted for 29% of cardiac and non-cardiac post-marketing withdrawals. The assessment of the effects of drugs on cardiac repolarization is the subject of recent guidelines and recommendations. Regulatory agencies now require practically every new pharmaceutical compound to undergo a thorough investigation of its propensity to modify cardiac repolarization. To reduce the incidence of QT prolongation and torsade de pointes in patients receiving AI, cancer patients should be closely monitored while receiving AI.


Asunto(s)
Inhibidores de la Angiogénesis/efectos adversos , Electrocardiografía/efectos de los fármacos , Corazón/efectos de los fármacos , Hipertensión/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de la Angiogénesis/administración & dosificación , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/terapia , Evaluación Preclínica de Medicamentos , Cardioversión Eléctrica , Corazón/fisiología , Humanos , Hipertensión/terapia , Magnesio/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Trombosis de la Vena/inducido químicamente , Trombosis de la Vena/tratamiento farmacológico , Disfunción Ventricular/inducido químicamente , Disfunción Ventricular/terapia , Privación de Tratamiento
12.
Clin Cancer Res ; 13(6): 1801-9, 2007 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-17363536

RESUMEN

PURPOSE: To determine the safety, maximum tolerated dose, pharmacokinetics, and efficacy, and to evaluate biomarkers, of the multikinase inhibitor sorafenib plus IFN alpha-2a in advanced renal cell carcinoma (RCC) or melanoma. EXPERIMENTAL DESIGN: Patients received 28-day cycles of continuous, oral sorafenib twice daily and s.c. IFN thrice weekly: sorafenib 200 mg twice daily plus IFN 6 million IU (MIU) thrice weekly (cohort 1); and sorafenib 400 mg twice daily plus IFN 6 MIU thrice weekly (cohort 2); or plus IFN 9 MIU thrice weekly (cohort 3). Tumor response was assessed by Response Evaluation Criteria in Solid Tumors and dynamic contrast-enhanced ultrasonography. RESULTS: Thirteen patients received at least one dose of sorafenib plus IFN (12 RCC; one melanoma). The maximum tolerated dose was not reached [only one dose-limiting toxicity (grade 3 asthenia)]. Most frequently reported drug-related adverse events were grade 2 or less in severity, including fatigue, diarrhea, nausea, alopecia, and hand-foot skin reaction. One (7.7%) RCC patient achieved partial response and eight (61.5%) had stable disease (including the melanoma patient). Good responders assessed by dynamic contrast-enhanced ultrasonography had increased progression-free survival and overall survival, relative to poor responders. IFN had no effect on the pharmacokinetics of sorafenib. There were no significant changes in absolute values of lymphocytes, levels of proangiogenic cytokines, or inhibition of phosphorylated extracellular signal-regulated kinase in T cells or natural killer cells, with combination therapy. CONCLUSIONS: This sorafenib combination was well tolerated, with preliminary antitumor activity in advanced RCC and melanoma patients. There were no drug-drug interactions and the recommended dose for future studies is sorafenib 400 mg twice daily plus IFN 9 MIU.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bencenosulfonatos/administración & dosificación , Carcinoma de Células Renales/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Neoplasias Renales/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Piridinas/administración & dosificación , Adulto , Anciano , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Bencenosulfonatos/efectos adversos , Bencenosulfonatos/farmacocinética , Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/patología , Femenino , Humanos , Sistema Inmunológico/efectos de los fármacos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Interferón-alfa/farmacocinética , Neoplasias Renales/patología , Masculino , Melanoma/patología , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Piridinas/efectos adversos , Piridinas/farmacocinética , Proteínas Recombinantes , Sorafenib , Resultado del Tratamiento
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