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1.
Clin Genitourin Cancer ; 13(2): 156-64.e1, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25444666

RESUMEN

BACKGROUND: Patients with advanced renal cell carcinoma in routine clinical practice can differ considerably from those in phase III studies. PATIENTS AND METHODS: PREDICT (Patient characteristics in REnal cell carcinoma and Daily practICe Treatment with sorafenib) was a prospective, noninterventional study of open-label sorafenib for the treatment of advanced RCC conducted in 18 countries. Patient characteristics, therapy duration, tumor status, and tolerability were assessed at baseline and during routine follow-up. RESULTS: Overall, 2599 patients were evaluable for safety and 2311 for efficacy. The diverse population included patients with brain metastases (5%), non-clear-cell histologies (17%), high Memorial Sloan-Kettering Cancer Center risk score (11%), poor Eastern Cooperative Oncology Group performance status (PS ≥ 2, 29%), and patients with no previous nephrectomy (16%) or no previous systemic therapy (37%). The median duration of sorafenib therapy was 7.3 months and was similar in clinically relevant subgroups (eg, patients with PS 2, brain metastases, or concomitant hypertension or diabetes [range, 6.7-7.0 months]). The median duration of therapy was shorter for patients with PS 3 or non-clear-cell histologies (4.6 and 4.8 months, respectively). The most common drug-related adverse events were hand-foot skin reaction (20%), diarrhea (17%), and rash (8%). CONCLUSION: Sorafenib was generally well tolerated and provided clinical benefit in a large, diverse population of patients with advanced RCC treated in routine clinical practice.


Asunto(s)
Antineoplásicos/administración & dosificación , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/etnología , Femenino , Humanos , Neoplasias Renales/etnología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/uso terapéutico , Estudios Prospectivos , Sorafenib , Resultado del Tratamiento , Adulto Joven
2.
Br J Cancer ; 110(12): 2821-8, 2014 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-24823696

RESUMEN

BACKGROUND: In the AXIS trial, axitinib prolonged progression-free survival (PFS) vs sorafenib in patients with advanced renal cell carcinoma (RCC) previously treated with sunitinib or cytokines. METHODS: In post hoc analyses, patients were grouped by objective response to prior therapy (yes vs no), prior therapy duration (< vs ⩾median), and tumour burden (baseline sum of the longest diameter < vs ⩾median). PFS and overall survival (OS), and safety by type and duration of prior therapy were evaluated. RESULTS: Response to prior therapy did not influence outcome with second-line axitinib or sorafenib. PFS was significantly longer in axitinib-treated patients who received longer prior cytokine treatment and sorafenib-treated patients with smaller tumour burden following sunitinib. Overall survival with the second-line therapy was longer in patients who received longer duration of prior therapy, although not significant in the sunitinib-to-axitinib sequence subgroup; OS was also longer in patients with smaller tumour burden, but not significant in the cytokine-to-axitinib sequence subgroup. Safety profiles differed modestly by type and duration of prior therapy. CONCLUSIONS: AXIS data suggest that longer duration of the first-line therapy generally yields better outcome with the second-line therapy and that lack of response to first-line therapy does not preclude positive clinical outcomes with a second-line vascular endothelial growth factor-targeted agent in patients with advanced RCC.


Asunto(s)
Carcinoma de Células Renales/tratamiento farmacológico , Imidazoles/uso terapéutico , Indazoles/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Axitinib , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Citocinas/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Imidazoles/efectos adversos , Indazoles/efectos adversos , Indoles/uso terapéutico , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Pirroles/uso terapéutico , Sorafenib , Sunitinib , Resultado del Tratamiento , Carga Tumoral
3.
Br J Cancer ; 108(8): 1571-8, 2013 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-23579211

RESUMEN

BACKGROUND: Axitinib demonstrated greater progression-free survival vs sorafenib in a phase III study of previously treated patients with metastatic renal cell carcinoma. Here, we report patient-reported kidney-specific symptoms and health status, measured by the Functional Assessment of Cancer Therapy (FACT) Kidney Cancer Symptom Index (FKSI) and the European Quality of Life self-report questionnaire (EQ-5D). METHODS: In all, 723 patients received axitinib (starting dose 5 mg twice daily (b.i.d.)) or sorafenib (400 mg b.i.d.). The FKSI-15, including the disease-related symptoms (FKSI-DRS) subscale, was administered on day 1 before dosing, every 4 weeks and at end of treatment (EOT)/withdrawal. Statistical methods included a mixed-effects repeated-measures model. RESULTS: At baseline, patients in both arms had relatively high mean FSKI-15 and FKSI-DRS scores, comparable to the general US population. Subsequent on-treatment overall mean scores were similar between axitinib and sorafenib, and there was no substantial decline during treatment. Scores substantially worsened at EOT, mainly due to disease progression. CONCLUSION: Patient-reported outcomes were comparable for second-line axitinib and sorafenib and were maintained at relatively high levels while on treatment, but worsened at EOT. As duration of treatment was longer with axitinib than sorafenib, time to worsening of symptoms can be delayed longer with axitinib.


Asunto(s)
Carcinoma de Células Renales/tratamiento farmacológico , Imidazoles/uso terapéutico , Indazoles/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Axitinib , Femenino , Humanos , Imidazoles/efectos adversos , Indazoles/efectos adversos , Masculino , Persona de Mediana Edad , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Autoinforme , Sorafenib , Resultado del Tratamiento , Adulto Joven
4.
Bull Cancer ; 97: 17-28, 2010.
Artículo en Francés | MEDLINE | ID: mdl-20418201

RESUMEN

Advanced renal cell carcinoma is associated with a poor prognosis and is refractory to standard chemotherapy. Recent progress in the understanding of molecular biology and pathogenesis of renal cell cancer has been translated into the development of new therapeutic strategies. The management of metastatic RCC has been revolutionized with the development of targeted molecular therapies against VEGF-VEGFR and mTOR. Randomized phase III clinical trials demonstrated clinical benefit for patients with advanced RCC in overall survival and progression free survival. At the moment, six molecules have been approves in advanced RCC: cytokines (IL-2 and IFN), antiangiogenic therapies (sunitinib, sorafenib, bevacizumab) and mTOR inhibitors (Temsirolimus, everolimus). Nephrectomy is an important component of the multimodality treatment of mRCC. Prospective trials will be assessed the value of nephrectomy in patients treated by antiangiogenic therapies. Large randomized trial are ongoing to evaluate these new therapies in adjuvant setting.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Bencenosulfonatos/uso terapéutico , Bevacizumab , Carcinoma de Células Renales/cirugía , Quimioterapia Adyuvante , Terapia Combinada , Everolimus , Humanos , Indoles/uso terapéutico , Interferones/uso terapéutico , Interleucina-2/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Renales/secundario , Neoplasias Renales/cirugía , Redes y Vías Metabólicas/efectos de los fármacos , Nefrectomía , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Piridinas/uso terapéutico , Pirroles/uso terapéutico , Sirolimus/análogos & derivados , Sirolimus/uso terapéutico , Sorafenib , Sunitinib , Serina-Treonina Quinasas TOR , Factor A de Crecimiento Endotelial Vascular/metabolismo
5.
Bull Cancer ; 97: 65-71, 2010.
Artículo en Francés | MEDLINE | ID: mdl-20418205

RESUMEN

The treatment of metastatic kidney cancer has dramatically changed in the last three years, with demonstration of efficacy of sunitinib, sorafenib, temsirolimus, bevacizumab combined with interferon and more recently everolimus. Although the international guidelines have recently been reviewed, some major questions are still open. Particularly, the best order of administration of these targeted therapies should be considered, since sequential schedule becomes usual with the availability of these new agents. At the same time, the tolerability and efficacy of the combination of the targeted therapies are under investigation in clinical trials. We report recent studies, mainly presented during the ASCO 2007 and 2008 congress. Furthermore, other studies are ongoing to answer other important questions, to optimize the treatment of this disease, such as the role of nephrectomy in case of synchronous metastatic disease, or the efficacy of the targeted therapies in different histological subtype than clear cell carcinoma, or in neoadjuvant and adjuvant settings.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bencenosulfonatos/uso terapéutico , Bevacizumab , Terapia Combinada , Citocinas/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Humanos , Indoles/uso terapéutico , Interferón-alfa/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Renales/metabolismo , Neoplasias Renales/cirugía , Nefrectomía , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Piridinas/uso terapéutico , Pirroles/uso terapéutico , Sirolimus/análogos & derivados , Sirolimus/uso terapéutico , Sorafenib , Sunitinib , Serina-Treonina Quinasas TOR , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismo
6.
Ann Oncol ; 21(5): 1027-31, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-19850637

RESUMEN

BACKGROUND: This retrospective study evaluated the incidence of brain metastases in a subgroup of patients with metastatic renal cell carcinoma (RCC) who were randomly assigned to receive sorafenib, an oral multikinase inhibitor (400 mg b.i.d.), versus placebo in the phase III Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET). PATIENTS AND METHODS: Patients enrolled in TARGET at two centres (Institut Gustave Roussy, Villejuif, France, n = 85; Central Clinical Hospital of Military Medical Academy, Warsaw, Poland, n = 54) made up the current subgroup, who were retrospectively evaluated for the incidence of brain metastases during follow-up. The association between treatment (sorafenib versus placebo) and occurrence of brain metastases was evaluated by univariate analysis. RESULTS: The overall incidence of brain metastases in patients receiving sorafenib was 3% (2 of 70 patients) compared with 12% (8 of 69 patients) in patients receiving placebo (P < 0.05). The incidence of brain metastases was also significantly lower in the sorafenib group after 1 (P = 0.0447) and 2 years (P = 0.005) of treatment compared with the placebo group. CONCLUSIONS: In this subpopulation, sorafenib may reduce the occurrence of brain metastases. Antiangiogenic therapy, such as sorafenib, could be an effective preventive therapy for brain metastases in advanced RCC.


Asunto(s)
Antineoplásicos/uso terapéutico , Bencenosulfonatos/uso terapéutico , Neoplasias Encefálicas/prevención & control , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Piridinas/uso terapéutico , Administración Oral , Anciano , Neoplasias Encefálicas/secundario , Carcinoma de Células Renales/secundario , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Neoplasias Renales/patología , Neoplasias Hepáticas/prevención & control , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Estudios Retrospectivos , Sorafenib , Tasa de Supervivencia
7.
Med Oncol ; 27(3): 899-906, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19757215

RESUMEN

Before the development of targeted therapies, administration of cytokines (e.g., interleukin-2, interferon-alpha) was the primary systemic treatment option for advanced renal cell carcinoma. Sorafenib, an oral targeted, multikinase inhibitor, significantly prolonged progression-free survival and overall survival in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET), a large (N = 903) phase III, double-blind, randomised, placebo-controlled study of patients with advanced renal cell carcinoma resistant to standard therapy. This analysis of a patient subgroup from TARGET evaluated the safety and efficacy of sorafenib in patients who had received prior cytokine therapy (sorafenib: n = 374; placebo: n = 368) and in patients who were cytokine-naïve (sorafenib: n = 77; placebo: n = 84). Progression-free survival was significantly prolonged with sorafenib therapy compared with placebo among patients with and without prior cytokine therapy (respectively 5.5 vs. 2.7 months; hazard ratio, 0.54; 95% confidence interval, 0.45-0.64 and 5.8 vs. 2.8 months; hazard ratio, 0.48; 95% confidence interval, 0.32-0.73). Clinical benefit rates for sorafenib-treated patients compared with placebo patients were also higher (cytokine-treated: 83 vs. 54.3%; cytokine-naïve: 85.7 vs. 56.0%). Sorafenib was well tolerated in both subgroups (grade 3/4: 20 and 22%, respectively). Sorafenib demonstrated a consistent, significant clinical benefit against advanced renal cell carcinoma, with a twofold improvement in progression-free survival and disease control rate, with similar toxicities in patients with or without prior cytokine treatment.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bencenosulfonatos/administración & dosificación , Bencenosulfonatos/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Diarrea/inducido químicamente , Supervivencia sin Enfermedad , Método Doble Ciego , Femenino , Enfermedades Hematológicas/inducido químicamente , Humanos , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Interleucina-2/administración & dosificación , Interleucina-2/efectos adversos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Progestinas/administración & dosificación , Progestinas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Piridinas/administración & dosificación , Piridinas/efectos adversos , Sorafenib , Resultado del Tratamiento , Alcaloides de la Vinca/administración & dosificación , Alcaloides de la Vinca/efectos adversos
8.
Ann Dermatol Venereol ; 135(10): 672-4, 2008 Oct.
Artículo en Francés | MEDLINE | ID: mdl-18929917

RESUMEN

BACKGROUND: Sorafenib is a new multikinase inhibitor recently approved for renal cell carcinoma and hepatocarcinoma. Among other targets, it blocks the kinase function of the RAF gene products including V600E mutant BRAF, which is frequently found in both melanoma and naevi. Cutaneous side effects are frequent with sorafenib, but no naevus modification has been reported until now. PATIENTS AND METHODS: Five cases of eruptive naevi in patients treated with sorafenib are reported. The mean duration of sorafenib treatment was 9.2 months when naevi eruption was noticed. The patients presented with about 100 to more than 200 small, homogenous, dark-brown naevi located mainly on the trunk and upper limbs. DISCUSSION: Eruptive melanocytic naevi have been reported in association with blistering diseases, and more generally in a setting of immunosuppression. We hypothesize that naevi appearance could be linked to an anti-senescence effect of sorafenib via its action on the MAP kinase pathway. Further prospective studies are needed to explore the relationship between sorafenib and the biology of naevi.


Asunto(s)
Antineoplásicos/efectos adversos , Bencenosulfonatos/efectos adversos , Nevo/inducido químicamente , Piridinas/efectos adversos , Neoplasias Cutáneas/inducido químicamente , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Sorafenib , Adulto Joven
9.
Ann Oncol ; 19(7): 1308-1311, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18356135

RESUMEN

BACKGROUND: Chemotherapy has emerged as a standard treatment in patients with castration-refractory prostate cancer (CRPC). Consensus criteria are available to define response in CRPC as at least a 50% decline in serum prostate-specific antigen (PSA) confirmed 4 weeks later. The objective of this work was to study early serum PSA changes in patients under chemotherapy and to correlate these changes with subsequent response assessment. PATIENTS AND METHODS: Serum PSA levels were monitored every 3 weeks in 79 patients with CRPC treated with chemotherapy and a time course of serum PSA levels was obtained. Correlation with response was studied. RESULTS: According to consensus criteria, 21 (40%) and 20 (38%) patients achieved a PSA response and stabilization, respectively, after first-line chemotherapy. Among patients who achieved either a response or a stabilization, 8 of 41 (20%) had a serum PSA rise during the first 8 weeks of chemotherapy, followed by a subsequent decline in serum PSA. The same observation was made in patients receiving second-line chemotherapy: 6 of 20 patients achieving a response or stabilization had an initial serum PSA rise. The postchemotherapy increase in serum PSA could reach more than twice the baseline value. The duration of the PSA surge ranged from 1 to 8 weeks. When considering responders only, 6 of 30 (20%) had a postchemotherapy serum PSA surge, followed by a drop. CONCLUSION: Postchemotherapy PSA surges occur not infrequently in patients with CRPC who respond to chemotherapy. Physicians should be aware of this effect to avoid inadequate early discontinuation of chemotherapy.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/secundario , Orquiectomía , Antígeno Prostático Específico/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Docetaxel , Estramustina/administración & dosificación , Hormona Liberadora de Gonadotropina/administración & dosificación , Humanos , Cinética , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/patología , Prednisona/administración & dosificación , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Sesquiterpenos/administración & dosificación , Síndrome , Taxoides/administración & dosificación , Resultado del Tratamiento
11.
Crit Care Med ; 26(3): 488-93, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9504577

RESUMEN

OBJECTIVES: To use three severity of illness scores to estimate the probability of hospital mortality among patients with cancer and neutropenia; to compare the performance of these scores, calculated at admission to an intensive care unit (ICU); and to test the improvement in estimation obtained by taking into account the first 72-hr period. DESIGN: Collection of data for every neutropenic patient hospitalized in the ICU during a 4-yr period. SETTING: A comprehensive cancer center. PATIENTS: Ninety-four patients were neutropenic at ICU admission. Their vital status was measured at hospital discharge. MEASUREMENTS AND MAIN RESULTS: The new Simplified Acute Physiology Score (SAPS) II improved the estimation of hospital mortality compared with the original SAPS score. Using a simple score based on the number of acute organ system failures (OSFs) to classify the patients, good discrimination between survivors and nonsurvivors was observed (area under the receiver operating characteristic curves, 79 +/- 5 [SD] %). The relationship between successive scores and outcome was explored using recursive partitioning. Patients were first classified according to their OSF value on the first day of hospitalization in the ICU with a cutoff of two organ failures, and classification was then improved by taking into account the OSF score on the third day. CONCLUSIONS: For cancer patients hospitalized in an ICU for a neutropenic episode, the severity of illness and the risk of death can be accurately assessed by the SAPS II score and the number of acute organ failures at admission. The OSF values on the first and third days of hospitalization both provided information, allowing the classification of patients into groups with different probabilities of hospital mortality.


Asunto(s)
Neoplasias/mortalidad , Neutropenia/complicaciones , Índice de Severidad de la Enfermedad , APACHE , Adolescente , Adulto , Anciano , Niño , Humanos , Unidades de Cuidados Intensivos , Persona de Mediana Edad , Neoplasias/complicaciones , Valor Predictivo de las Pruebas , Curva ROC , Factores de Riesgo , Tasa de Supervivencia
12.
J Immunother ; 21(1): 62-4, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9456438

RESUMEN

Interferon-alpha is an accepted treatment for renal cell carcinoma, with a response rate approximately 14%. Retinoic acid has been claimed to improve such a response rate when combined with interferon. We present the results of a phase II study combining interferon alpha and all-trans retinoic acid (ATRA) in patients with metastatic renal cell carcinoma. Thirty-one patients who were not eligible for a trial of high-dose interleukin-2 treatment (because of low performance status: 7 patients; prior immunotherapy: 11 patients; age > 70: 8 patients, cardiac or respiratory failure: 4 patients; refusal for randomization: 1 patient) were enrolled in this study. Only one partial response was observed (3%). Despite the good tolerance observed with this association, ATRA does not improve the efficacy of interferon in this selected patient population (with poor prognosis). Such a treatment combination should not be further recommended in patients with metastatic renal cell carcinoma.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Neoplasias Renales/tratamiento farmacológico , Tretinoina/administración & dosificación , Adulto , Anciano , Carcinoma de Células Renales/secundario , Femenino , Humanos , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Inducción de Remisión , Tretinoina/uso terapéutico
13.
Eur J Cancer ; 33(7): 1031-7, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9376183

RESUMEN

The admission of neutropenic patients to an intensive care unit (ICU) is still controversial, especially if mechanical ventilation is required. To avoid useless stays in ICU, the evaluation of the respective role of the underlying malignancy and acute organ failures might be useful for better definition of the categories of patients who could benefit from aggressive ICU support. For this purpose, we carried out a retrospective study of the charts of 107 consecutive neutropenic patients admitted to an ICU in a comprehensive cancer centre over a four-year period. The following characteristics were recorded within 24 h of admission: patient data, characteristics of neutropenia and the underlying malignancy, the type and number of organ system failures (OSFs) and simplified acute physiological scores (SAPS and SAPS II). The impact of each variable on outcome in the ICU was studied by univariate and multivariate (logistic regression) analysis. 59 patients died in the ICU (mortality rate: 55%). Patients with a haematological malignancy (n = 57, 53%) were more likely to experience respiratory failure, an underlying malignancy deemed rapidly fatal, and to have longer lasting neutropenia than patients with a solid tumour (n = 50, 47%). However, the mortality rate did not differ in the two groups (haematological malignancy 61% versus solid tumour 48%, p = 0.16). Respiratory and cardiovascular organ failure (p < 0.001 for both) correlated with mortality in the ICU. In the multiple logistic regression model, only the number of organ system failures and respiratory failure remained predictive of ICU mortality. In conclusion, the characteristics of the underlying malignancy are not relevant when deciding whether or not neutropenic patients should be admitted to an ICU. The main risk factors for death in an ICU are the number of organ failures on admission, and among them the presence of respiratory failure.


Asunto(s)
Cuidados Críticos , Neoplasias/complicaciones , Neutropenia/mortalidad , Adulto , Antineoplásicos/efectos adversos , Femenino , Humanos , Modelos Logísticos , Masculino , Insuficiencia Multiorgánica/complicaciones , Análisis Multivariante , Neoplasias/mortalidad , Neutropenia/inducido químicamente , Neutropenia/complicaciones , Neutropenia/terapia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Resultado del Tratamiento
14.
Biotherapy ; 5(1): 11-20, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1389899

RESUMEN

We have attempted to improve negative selection procedures for the large scale purification of human CD-3 CD56+ NK cells. In a series of experiments, purifications of NK cells from 10(8) PBMC were performed by T cell depletion using either direct or indirect anti-CD3 labeling and the Magnetic Activated Cell Separation (MACS) procedure. Contaminating CD3+ cells were still present using either one of these two different T cell depletion protocols as shown by phenotyping IL-2 supplemented cell cultures on day 12. A second cycle of purification was therefore added. When MACS and Dynabeads were compared as complementary procedures to the first MACS cycle starting with 10(8) cells, the Dynabeads method was found to be superior to the MACS with regard to the elimination of residual T cells. Starting from 10(9) PBMC, we showed that this MACS+Dynabeads procedure gave similar satisfactory results when compared to the scaling-up of a previously established two steps procedure using Dynabeads. These two approaches (MACS+Dynabeads and 2 cycles of Dynabeads) have been also tested in a clinical setting to purify NK cells from cancer patients prior to in vitro expansion. The results indicate that the two methods are equivalent with respect to purity and recovery rate; a slight advantage in terms of feasibility was found in favor of 2 cycles of Dynabeads.


Asunto(s)
Separación Celular/métodos , Células Asesinas Naturales/citología , Animales , Anticuerpos Monoclonales , Biotina , Complejo CD3/inmunología , Recuento de Células , Cabras , Humanos , Leucocitos Mononucleares/citología , Magnetismo , Ratones , Formación de Roseta/métodos , Linfocitos T/citología
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