Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

Transition of Adolescents With Severe Asthma From Pediatric to Adult Care in Spain: The STAR Consensus.

OBJECTIVES: To assess the degree of consensus among a multidisciplinary expert panel on the transition of adolescents with severe asthma from pediatric to adult care. METHODS: A 61-item survey was developed based on guidelines for other chronic diseases, covering transition planning, preparation, effective transfer, and follow-up. A 2-round Delphi process assessed the degree of consensus among 98 experts (49 pediatricians, 24 allergists, and 25 pulmonologists). Consensus was established with ≥70% agreement. RESULTS: Consensus was reached for 42 items (70%). Panelists were unable to agree on an age range for initiation of transition. The main goal during the transition identified by the experts is for adolescents to gain autonomy in managing severe asthma and prescribed treatments. The panelists agreed on the importance of developing an individualized plan, promoting patient autonomy, and identifying factors associated with the home environment. They agreed that the adult health care team should have expertise in severe asthma, biologics, and management of adolescent patients. Pediatric and adult health care teams should share clinical information, agree on the criteria for maintaining biological therapy, and have an on-site joint visit with the patient before the effective transfer. Adult health care professionals should closely follow the patient after the effective transfer to ensure correct inhaler technique, adherence, and attendance at health care appointments. CONCLUSION: This consensus document provides the first roadmap for Spanish pediatric and adult teams to ensure that key aspects of the transition process in severe asthma are covered. The implementation of these recommendations will improve the quality of care offered to the patient.

Beneficios de la musicoterapia en las alteraciones conductuales de la demencia. Revisión sistemática / Benefits of music therapy on behaviour disorders in subjects diagnosed with dementia: a systematic review

Introducción. La demencia se caracteriza por un deterioro cognitivo y por la aparición de síntomas psicológicos y conductuales, entre los que destacan las alteraciones de percepción, del contenido del pensamiento, estado de ánimo y de conducta. Para tratar estos síntomas, además del tratamiento farmacológico, se utilizan intervenciones no farmacológicas, entre ellas la musicoterapia. Esta técnica novedosa, por sus características no verbales, puede ser usada en todas las fases del tratamiento de las personas con demencia ya que, aunque haya un gran deterioro cognitivo, las respuestas ante la música se mantienen hasta los estadios más avanzados de la enfermedad. Desarrollo. Se realizó una búsqueda bibliográfica con un intervalo temporal entre 2003 y 2013 en las bases de datos Academic Search Complete, PubMed, Science Direct y Dialnet. Los términos de búsqueda incluyeron la combinación de las palabras claves «music therapy, dementia, behaviour, behavioural disorders y behavioural disturbances». Se seleccionaron 11 registros de los 2188 localizados tras aplicar los criterios de inclusión. Conclusiones. El tratamiento con musicoterapia es beneficioso para mejorar las alteraciones conductuales, la ansiedad y la agitación en pacientes con demencia (AU)

Introduction. Dementia is characterised by cognitive deterioration and the manifestation of psychological and behavioural symptoms, especially changes in perception, thought content, mood, and conduct. In addition to drug therapy, non-pharmacological treatments are used to manage these symptoms, and one of these latter treatments is music therapy. Since this novel technique in non-verbal, it can be used to treat patients with dementia at any stage, even when cognitive deterioration is very severe. Patients’ responses to music are conserved even in the most advanced stages of the disease Development. A literature research was carried out using the following databases: Academic Search Complete, PubMed, Science Direct y Dialnet. The period of publication was 2003 to 2013 and the search keywords were «Music Therapy, Dementia, Behaviour, Behaviour Disorders y Behavioural Disturbances». Out of the 2188 studies that were identified, 11 studies met inclusion criteria for the systematic review. Conclusions. Music therapy is beneficial and improves behavior disorders, anxiety and agitation in subjects diagnosed with dementia (AU)

Benefits of music therapy on behaviour disorders in subjects diagnosed with dementia: a systematic review. / Beneficios de la musicoterapia en las alteraciones conductuales de la demencia. Revisión sistemática.

INTRODUCTION: Dementia is characterised by cognitive deterioration and the manifestation of psychological and behavioural symptoms, especially changes in perception, thought content, mood, and conduct. In addition to drug therapy, non-pharmacological treatments are used to manage these symptoms, and one of these latter treatments is music therapy. Since this novel technique in non-verbal, it can be used to treat patients with dementia at any stage, even when cognitive deterioration is very severe. Patients' responses to music are conserved even in the most advanced stages of the disease DEVELOPMENT: A literature research was carried out using the following databases: Academic Search Complete, PubMed, Science Direct y Dialnet. The period of publication was 2003 to 2013 and the search keywords were 'Music Therapy, Dementia, Behaviour, Behaviour Disorders y Behavioural Disturbances'. Out of the 2188 studies that were identified, 11 studies met inclusion criteria for the systematic review. CONCLUSIONS: Music therapy is beneficial and improves behavior disorders, anxiety and agitation in subjects diagnosed with dementia.

Hyperthermic intraperitoneal chemotherapy with paclitaxel or cisplatin in patients with stage III-C/IV ovarian cancer. Is there any difference?

OBJETIVE: To compare the results of the administration of HIPEC with Paclitaxel or Cisplatin after cytoreduction in patients with stage IIIC-IV ovarian cancer, especially focused on disease-free survival. PATIENTS: We retrospectively analyzed a consecutive series of patients operated after being diagnosed with stage III-C/IV serous epithelial ovarian carcinoma. Patients included in the study were treated between January 2008 and March 2015. After cytoreduction, Paclitaxel (doses of 60 mg/m(2)O or Cisplatin (doses of 75 mg/m(2)) were used. RESULTS: A total of 111 patients were included. Median age was 61 years. In 60 of them (54%) Paclitaxel was used during HIPEC treatment and 51 patients (46%) were treated with Cisplatin. PCI was similar between groups (PCI = 11 in both cases). Median follow up was 34 months (12-96 months). The median disease free survival in Paclitaxel Group was 27 months and 33 months in Cisplatin Group (p = 0.551). In patients treated with Paclitaxel disease free survival rates at 1, 2, and 3 years were 79%, 60% and 46%. In patients treated with Cisplatin disease free survival at 1, 2, and 3 years were 64%, 50% and 40% respectively. After a multivariate analysis, incomplete cytoreduction (HR: 6.54, 95% CI 2.98-10.17, p < 0.01) and PCI >11 (HR: 2.15, 95% CI 1.42-6.68, p < 0.05) were identified as independent factors associated with a reduced disease-free survival. Cystotatic used was not relevant regarding disease free survival analysis. CONCLUSION: HIPEC with paclitaxel or cisplatin after cytoreduction in patients with ovarian cancer IIIC-IV has not shown different results in disease-free survival outcomes.

The role of hyperthermic intraperitoneal chemotherapy using paclitaxel in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction.

BACKGROUND: We analyzed the role of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) on the microscopic component of the disease in patients with a first recurrence of platinum-sensitive ovarian cancer after complete cytoreduction (CCR). PATIENTS AND METHODS: We analyzed the data of 54 patients who were operated on between January 2001 and July 2012 with the diagnosis of platinum-sensitive recurrent ovarian cancer. In all patients, it was possible to achieve a CCR. Patients were divided into two groups: group I (cytoreduction alone) consisted of 22 surgical patients and group II (cytoreduction and HIPEC) consisted of 32 patients. RESULTS: There were no significant differences in any of the preoperative variables studied. After a multivariate analysis of factors identified in the univariate analysis, only the presence of tumors with undifferentiated histology (hazard ratio 2.57; 95% CI 1.21-5.46; p < 0.05) was an independent factor associated with a reduced disease-free survival. The 1- and 3-year disease-free survival was 77 and 23% in patients from group I and 77 and 45% in patients from group II, respectively, with a tendency, but no significant differences (p = 0.078). There was no significant difference in postoperative morbidity between the two groups. CONCLUSIONS: The administration of HIPEC in patients in whom it is possible to achieve a CCR of the disease has not increased postoperative morbidity and mortality rates in our center. HIPEC with paclitaxel is effective in the treatment of microscopic disease in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction, although with no statistically significant difference.

Síndrome de apnea obstructiva del sueño en niños (SAOS) / Obstructive sleep apnea syndrome in children (OSAS)

El síndrome de la apnea obstructiva del sueño (SAOS) es ocasionado por una obstrucción de las vías aéreas superiores, resultado de un desequilibrio entre la fuerza de succión respiratoria y la compensación de los músculos dilatadores faríngeos. El diagnóstico positivo es establecido por el registro polisomnográfico nocturno durante el sueño que define las características y la severidad de esta enfermedad. El objetivo del siguiente artículo es difundir los diversos aspectos clínicos y diagnósticos de una enfermedad recientemente descripta de alta prevalencia y que cruza las fronteras de múltiples especialistas (pediatras, neurólogos, neumólogos, otorrinolaringólogos, psiquiatras, psicólogos, odontoestomatólogos, ortodoncistas), así contribuiremos a su diagnóstico precoz a partir de los niños que roncan, evitando las importantes secuelas del SAOS infantil...

Uranium and thorium sequential separation from norm samples by using a SIA system.

This study presents a sequential radiochemical separation method for uranium and thorium isotopes using a novel Sequential Injection Analysis (SIA) system with an extraction chromatographic resin (UTEVA). After the separation, uranium and thorium isotopes have been quantified by using alpha-particle spectrometry. The developed method has been tested by analyzing an intercomparison sample (phosphogypsum sample) from International Atomic Energy Agency (IAEA) with better recoveries for uranium and thorium than the obtained by using a classical method (93% for uranium using the new methodology and 82% with the classical method, and in the case of thorium the recoveries were 70% for the semi-automated method and 60% for the classical strategy). Afterwards, the method was successfully applied to different Naturally Occurring Radioactive Material (NORM) samples, in particular sludge samples taken from a drinking water treatment plant (DWTP) and also sediment samples taken from an area of influence of the dicalcium phosphate (DCP) factory located close to the Ebro river reservoir in Flix (Catalonia). The obtained results have also been compared with the obtained by the classical method and from that comparison it has been demonstrated that the presented strategy is a good alternative to existing methods offering some advantages as minimization of sample handling, reduction of solvents volume and also an important reduction of the time per analysis.

Intestinal anti-inflammatory activity of combined quercitrin and dietary olive oil supplemented with fish oil, rich in EPA and DHA (n-3) polyunsaturated fatty acids, in rats with DSS-induced colitis.

BACKGROUND AND AIMS: Previous studies have described the intestinal anti-inflammatory effects exerted by the bioflavonoid quercitrin (QR) and by an n-3 polyunsaturated fatty acids (PUFA)-enriched diet in experimental models of rat colitis. The aim of the present study was to test if the combination of both treatments would result in an improvement in the intestinal anti-inflammatory effect achieved separately. METHODS: Colitis was induced in female Wistar rats by incorporating dextran sodium sulfate (DSS) in drinking water at 5% (w/v) for 5 days and at 2% (w/v) for the following 10 days. Five groups of rats (n=10) were used: two of them received an olive-oil-based diet with fish oil, rich in n-3 PUFA (FO diet) for 2 weeks before colitis induction and until the end of the experiment, and one of those also was administered daily QR (1mg/kg, PO), starting when DSS concentration was changed. DSS colitis was induced in other two groups fed with standard rat diet, one of them being administered QR as before. A non-colitic group fed standard diet was also included. After that period, the rats were sacrificed and colonic damage was assessed both histologically and biochemically. RESULTS: The concurrent administration of FO diet and QR exhibited an intestinal anti-inflammatory effect, as evidenced by a significant improvement of all biochemical parameters of colonic inflammation assayed in comparison with non-treated colitic rats. Thus, both colonic myeloperoxidase (MPO) and alkaline phosphatase (AP) activities were significantly reduced compared with untreated colitic rats. In addition, a complete restoration of colonic glutathione content, which was depleted as a consequence of the colonic insult, was obtained in rats treated with QR plus FO diet; this content was even higher than that obtained when colitic rats were treated with FO diet alone. When compared with the control colitic group, the combined treatment was also associated with a lower colonic nitric oxide synthase and cyclooxygenase-2 expression as well as with a significant reduction in different colonic proinflammatory mediators assayed, i.e. leukotriene B(4), tumor necrosis factor alpha and interleukin 1beta, showing a significantly greater inhibitory effect of the latter in comparison with rats receiving FO diet without the flavonoid. CONCLUSIONS: These results support the potential synergism between the administration of the flavonoid and the incorporation of olive oil and n-3 PUFA to the diet for the treatment of these intestinal inflammatory disorders.

Leiomiosarcoma de la vulva / Leiomyosarcoma of the vulva

Se presenta un caso de leiomiosarcoma de la vulva (LMS-V), tumor maligno de frecuencia excepcional; según la extensa revisión bibliográfica efectuada, el aquí recogido tendría el número 47 de los publicados. El seguimiento comprende más de 5 años y la evolución ha sido favorable. Se analizan la apariencia clínica de benignidad, los criterios histológicos para su caracterización y gradación histológicas y los tratamientos empleados, de los cuales el tratamiento quirúrgico primario con suficiente margen de seguridad parece ser el más eficaz para conseguir una evolución favorable (AU)

Acroqueratoelastoidosis de Costa / Acrokeratoelastoidosis

La acroqueratoelastoidosis (AKE) de Costa es una forma de queratodermia palmopalmar poco frecuente que puede aparecer de forma esporádica o tener un patrón autosómico dominante. Rara vez está presente en el nacimiento; en la mayoría de las ocasiones lo hace a partir de la adolescencia en forma de pápulas translúcidas, amarillentas o del color de la piel normal. Tienen una localización típica en las eminencias tenar e hipotenar, pudiendo también afectar las palmas de las manos y las zonas laterales de los dedos. La asociación de hiperhidrosis es un hecho habitual. Histológicamente, los datos más característicos son hiperqueratosis, discreta acantosis, fragmentación y desestructuración de las fibras elásticas de la dermis reticular. Los tratamientos son pocos eficaces. Comentamos el caso de una niña de 10 años afectada por esta enfermedad y revisamos el diagnóstico diferencial con el grupo de las llamadas acroqueratodermias papulares marginales (AU)

[Importance of the integrated evaluation of the child with asthma]. / Importancia de la evaluación integral del niño con asma.

When evaluating the effects of the practical application of a therapeutic strategy, the results of the controlled and random clinical tests with the above mentioned treatment, as they are important, do not constitute the only factor to be considered. Especially as frequently the clinical tests only take into account the efficiency of the treatment, without considering other essential aspects such as safety, performance and cost. The combination of these factors results in the PRACTICAL efficiency of the treatment, that often differs considerably from the results obtained in clinical tests. Therefore, the clinical tests do not precisely reflect the conditions that exist when a treatment is applied in real life and thus, the evaluation of the practical efficiency of the said treatment is essential if you want to know what the real repercussion that the treatment has on a specific problem, such as asthma, represents. And this is important as, in spite of the notable advances over the last few years in the treatment of this illness, the objectives that the GINA propose in order to consider the control of asthma as sufficient, are a long way from being achieved, as the results of the AIRE study that was carried out in 7 European countries illustrate. On the other hand, the valuation of the efficiency of a treatment is a problem that is worth discussing. As, due to operational and precision reasons, of then the clinical tests consider one or a few variables as objectively as possible (for example, the lung function) when valuing the efficiency of a treatment. However, on many occasions it is possible to appreciate notable discrepancies between these objective variables and the patient's symptoms, the subjective appreciation of how the asthma is affecting them, etc. Therefore, it is necessary to take into account the fact that an integral valuation of the repercusion that asthma has on the patients, their families and their environment, and how a specific treatment changes the situation on these levels, and obligues us to consider in an integral manner, a series of medical (clinical, functional and biological), humanistic (quality of life, patients satisfaction) and economic variables.

Importancia de la evaluación integral del niño con asma / Importance of the integrated evaluation of the child with asthma

A la hora de evaluar los efectos de la aplicación práctica de una estrategia terapéutica, los resultados de los ensayos clínicos controlados y aleatorios con el citado tratamiento, con ser muy importantes, no constituyen el único factor a considerar. Especialmente porque, con frecuencia, los ensayos clínicos tienen en cuenta de forma exclusiva la eficacia del tratamiento, sin considerar otros aspectos esenciales como la seguridad, el cumplimiento y el costo. La combinación de estos factores tiene como resultado la eficacia PRÁCTICA del tratamiento, que con frecuencia difiere grandemente de los resultados obtenidos en los ensayos clínicos. Así pues, los ensayos clínicos no reflejan con precisión las condiciones en las que un tratamiento se aplica en la vida real y por ello, la evaluación de la eficacia práctica de dicho tratamiento resulta esencial si se quiere conocer cuál es la repercusión real que el mismo tiene sobre un problema concreto como es el asma. Y ello es importante porque, a pesar de los notables avances de los últimos años en el tratamiento de esta enfermedad, los objetivos que se plantea la GINA para considerar como adecuado el control del Asma están lejos de ser conseguidos, como ilustran los resultados del estudio AIRE, llevado a cabo en siete países europeos.Por otra parte, la valoración de la eficacia de un tratamiento resulta un problema que merece discusión. Porque, por razones de operatividad y precisión, con frecuencia los ensayos clínicos consideran una o unas pocas variables lo más objetivas posible (ej. función pulmonar) a la hora de valorar la eficacia de un tratamiento. No obstante, muchas veces es posible apreciar notables discrepancias entre los valores de estas variables objetivas, y los síntomas de los pacientes, la apreciación subjetiva de cómo el asma les está afectando, etc. Por ello, es necesario tener en cuenta que una valoración integral de la repercusión que el asma tiene sobre los pacientes, sus familias y su entorno, y de cómo un determinado tratamiento modifica la situación a estos niveles, obliga a considerar de forma integrada una serie de variables médicas (clínicas, funcionales y biológicas), humanísticas (calidad de vida, satisfacción del paciente) y económicas. (AU)

When evaluating the effects of the practical application of a therapeutic strategy, the results of the controlled and random clinical tests with the above mentioned treatment, as they are important, do not constitute the only factor to be considered. Especially as frequently the clinical tests only take into account the efficiency of the treatment, without considering other essential aspects such as safety, performance and cost. The combination of these factors results in the PRACTICAL efficiency of the treatment, that often differs considerably from the results obtained in clinical tests. Therefore, the clinical tests do not precisely reflect the conditions that exist when a treatment is applied in real life and thus, the evaluation of the practical efficiency of the said treatment is essential if you want to know what the real repercussion that the treatment has on a specific problem, such as asthma, represents. And this is important as, in spite of the notable advances over the last few years in the treatment of this illness, the objectives that the GINA propose in order to consider the control of asthma as sufficient, are a long way from being achieved, as the results of the AIRE study that was carried out in 7 European countries illustrate. On the other hand, the valuation of the efficiency of a treatment is a problem that is worth discussing. As, due to operational and precision reasons, of then the clinical tests consider one or a few variables as objectively as possible (for example, the lung function) when valuing the efficiency of a treatment. However, on many occasions it is possible to appreciate notable discrepancies between these objective variables and the patient's symptoms, the subjective appreciation of how the asthma is affecting them, etc. Therefore, it is necessary to take into account the fact that an integral valuation of the repercusion that asthma has on the patients, their families and their environment, and how a specific treatment changes the situation on these levels, and obligues us to consider in an integral manner, a series of medical (clinical, functional and biological), humanistic (quality of life, patients satisfaction) and economic variables (AU)

[Cystic fibrosis: nutritional aspects and recommendations]. / Fibrosis quística: aspectos y recomendaciones nutricionales.

Given the high numbers of nutritional supplements and enteral diets which are supplied for patients suffering from cystic fibrosis, by the departments of hospital pharmacy, the present study aims to review which are the characteristics of this disease which determine the appearance of malnutrition in these patients. Also, their nutritional treatment has been reviewed. On one hand, considering the general dietary measures, keeping in mind the composition of the diets, their characteristics according to age, and the supplementation with vitamins and with pancreatic enzymes. On the other hand, there is a review of the special dietary measures which should be applied in case of failure to thrive of the child, which goes from the modification of the oral diet, to the administration of parenteral nutrition.

Neoadjuvant chemotherapy with continuous infusion of cisplatin and 5-fluorouracil, with or without leucovorin, for locally advanced nasopharyngeal carcinoma.

Cisplatin-based induction chemotherapy has been extensively tested in nasopharyngeal carcinoma for the improvement of local and systemic control and survival of this disease. In this study, we report the results of the treatment with induction chemotherapy in 40 patients with locally advanced carcinoma of the nasopharynx (LANPC) with four courses of cisplatin (P) 25 mg/m2 per day and 5-fluorouracil (F) 1000 mg/m2 per day both in a 4-days continuous infusion, with or without leucovorin (L) 250 mg/m2 per day in 2-hour infusion at the beginning of daily administration of PF, followed by sequential radiotherapy. All except one were in stage IV. The overall response after induction chemotherapy was 93%, with 55% CR and 38% PR. Definitive overall response after radiotherapy was 98%, with 80% CR and 18% PR. At a maximum follow up of 11 years, the overall survival rate is 55%. Induction chemotherapy with continuous infusion of PF with or without leucovorin followed by radiotherapy is a highly active regimen for the treatment of locally advanced nasopharyngeal carcinoma with response and survival rates comparable to other combinations of sequential or simultaneous chemotherapy and radiotherapy.

Four days' continuous infusion of cisplatin-5-fluorouracil and short daily infusion of high-dose leucovorin as induction chemotherapy for locally advanced head and neck cancer.

Cisplatin-fluorouracil (PF) is the most frequently used combination as induction chemotherapy (CT) for the treatment of locally advanced squamous cell head and neck cancer. This study was designed to evaluate the role of leucovorin (L) in the modulation of the therapeutic activity of PF continuously infused for 4 days. Between June 1990 and June 1992, stage III and IV previously untreated patients received PFL induction chemotherapy followed by surgery, radiotherapy, or both. The chemotherapy consisted of P 25 mg/m2, F 1000 mg/m2 both continuously infused for 4 days and L 250 mg/m2 infused for 2 hours before each daily infusion of PF. PFL was administered every 3 weeks for 4 cycles. The overall response rate at the completion of PFL was 91%, with 54% CR and 37% PR. Locoregional treatment was performed on 68 patients, 11 (16%) underwent surgery, 20 (29%) surgery plus radiotherapy, and 37 (54%) radiotherapy. Complete response status after both induction and locoregional therapy was 71%. Biopsies of the primary tumor or definitive resection specimens immediately after PFL therapy were available in 25 patients in CR. Pathological CR was found in 11 (44%). With a maximum follow-up of 44 months, the overall survival rate is 51% and the median survival has not been reached. PFL is highly active as induction chemotherapy. A randomized comparison between PF and PFL is necessary to define the place of leucovorin modulation in the treatment of head and neck cancer.