geno5mC: A Database to Explore the Association between Genetic Variation (SNPs) and CpG Methylation in the Human Genome.

Genetic variation, gene expression and DNA methylation influence each other in a complex way. To study the impact of sequence variation and DNA methylation on gene expression, we generated geno5mC, a database that contains statistically significant SNP-CpG associations that are biologically classified either through co-localization with known regulatory regions (promoters and enhancers), or through known correlations with the expression levels of nearby genes. The SNP rs727563 can be used to illustrate the usefulness of this approach. This SNP has been associated with inflammatory bowel disease through GWAS, but it is not located near any gene related to this phenotype. However, geno5mC reveals that rs727563 is associated with the methylation state of several CpGs located in promoter regions of genes reported to be involved in inflammatory processes. This case exemplifies how geno5mC can be used to infer relevant and previously unknown interactions between described disease-associated SNPs and their functional targets.

Análisis de parámetros de función pulmonar en nadadores de piscinas cubiertas / Lung functional parameters in users of indoor swimming pools

OBJETIVO: Es controvertido el efecto que la natación en piscinas cubiertas puede tener sobre la función pulmonar y sobre los parámetros de inflamación bronquial. El objetivo del estudio fue estudiar la evolución de parámetros funcionales y de inflamación antes y después del baño en usuarios de piscinas cubiertas y sin patología respiratoria conocida. METODOLOGÍA: Estudio observacional prospectivo en el que se incluyeron nadadores habituales de piscinas cubiertas. Los individuos incluidos en el estudio no presentaban antecedentes de asma ni alteraciones funcionales o de inflamación bronquial en el momento de la inclusión. Se realizaron pruebas funcionales (espirometría) y medida de inflamación (FeNO) minutos antes y tras el baño en diferentes piscinas públicas. Se analizaron de forma paralela los parámetros físico-químicos del agua de dichas piscinas en el momento de la natación y que fueron proporcionados por la Inspección de Sanidad adscrita a dicha piscina pública. RESULTADOS: Fueron incluidos 50 nadadores, 26 hombres y 24 mujeres, de edad media 40,8 ± 10,8 años. El tiempo de inmersión fue de 32 minutos. Encontramos diferencias antes y tras la inmersión. En los nadadores incluidos mejoraron tras la inmersión de forma significativa la FVC (p < 0,05), y el FEV1 (p < 0,04) así como disminuyó el FENO (p < 0,01) Las características del agua de las piscinas, medidas según los protocolos habituales de sanidad, se encontraron en todos los casos dentro del rango habitual determinados en el Real Decreto 742/2013, de 27 de septiembre (BOE, Viernes 11 de octubre de 2013), por el que se establecen los criterios técnico-sanitarios de las piscinas. Tras el análisis estadístico, no se obtuvieron diferencias en parámetros de función e inflamación bronquial en relación con los datos físicos y químicos del agua de las piscinas y recogidos en el momento de la inclusión de los pacientes en el estudio. CONCLUSIONES: Hemos objetivado una mejoría significativa de los parámetros funcionales respiratorios en nadadores de piscinas cubiertas

INTRODUCTION: it is controversial the effect that swimming in indoor swimming pool can have on lung function and parameters of inflammation. The objective of the study was to study the evolution of functional parameters and inflammation before and after swimming in users of indoor swimming pools and without known respiratory pathology. MATERIAL AND METHODS: this was an observational prospective study in which regular swimmers were included. Individuals included in the study had no history of asthma or functional or inflammatory diseases at the time of inclusion. Functional tests (spirometry) and inflammation measurement (FENO) were performed minutes before and after bathing in different public swimming pools. The physical-chemical parameters of the water of these swimming pools were analyzed in parallel at the time of swimming and were provided by the sanitary inspection attached to said public swimming pool. RESULTS: were included 50 swimmers, 26 men and 24 women, mean age 40.8 ± 10.8 years. The immersion time was 32 minutes. In the swimmers included, FVC significantly improved after dipping (p < 0.05), FEV1 (p < 0.04) as did FENO (p < 0.01). The water characteristics of the swimming pools, measured according to the usual health protocols, were found in all cases within the usual range determined in Royal Decree 742/2013, de 27th September (BOE 11th October 2013). After statistical analysis, no differences were found in parameters of bronchial function and inflammation in relation to the physical and chemical data of the swimming pools included in the study. CONCLUSIONS: we have observed a significant improvement in respiratory functional parameters in indoor swimming pool swimmer

Patient satisfaction in a Spanish burn unit.

BACKGROUND: As a result of the Spanish healthcare system overhaul, quality of care is becoming increasingly important. All burn service providers are required to measure patient satisfaction with care as an imperative need. Nevertheless, there are very few papers regarding patient satisfaction in burn units or in plastic surgery in general. The aim of this study is to examine patient satisfaction in our burn unit and to identify areas for improvement. MATERIALS AND METHODS: Participants were all patients admitted to the Burn Unit at the Getafe University Hospital (Madrid, Spain) between January 2014 and December 2016. Patient satisfaction was assessed using the SERVQHOS questionnaire and Kano methodology. The SERVQHOS questionnaire was given to all patients at the time of discharge with completion thereof voluntary and anonymous. The Kano model consisted of an in-depth personal interview with patients and their relatives to identify patient requirements. Further, we developed a Kano questionnaire and analysed the results to prioritise the requirements for development activities. RESULTS: A total of 164 SERVQHOS questionnaires were collected, which means 58% of the discharged patients who were asked to participate returned the questionnaire. Mean overall satisfaction score was 3.7 (range 1-4). Ninety-seven per cent of patients would not hesitate to recommend the hospital to others, 90% believed they had stayed in the hospital for the time necessary and 89% did not have any pain relief problems. The issues that were rated the worst by users were those related to objective quality such as room conditions, location directions, ease of discharge from the hospital and employee appearance. The best-valued aspects were those related to subjective quality such as willingness to help patients, ability to inspire trust and confidence, courtesy and personal attention. CONCLUSIONS: Patients hospitalised in our burn unit are highly satisfied with the care they receive, especially with regard to subjective quality. The evaluation of the satisfaction outcomes helped us to identify several strengths and weaknesses in the healthcare services we provide as well as strategies to improve the weaknesses. Evaluating care quality and patient satisfaction in any burn unit is appropriate and recommendable given that it offers clients' first-hand opinions.

Reconstrucción fálica total con colgajo libre antebraquial radial tras amputación peneana iatrogénica / Total phallic reconstruction using radial forearm free flap after iatrogenic penile amputation

Introducción: La pérdida del pene de causa iatrogénica es una circunstancia muy infrecuente. Se presenta un caso desafiante de reconstrucción peneana total diferida en varón genético. Material y métodos: Varón de 57 años con pérdida del falo por absceso peneano y necrosis secundaria a cirugía de incurvadura peneana. La reconstrucción se realizó en varios tiempos empleando colgajo libre de antebrazo radial (CLAR) y colocación de prótesis inflable personalizada un año después. Resultados: En un primer tiempo quirúrgico se llevó a cabo drenaje de absceso peneano, desbridamiento de restos necróticos y colocación de talla hipogástrica. Siete semanas después se llevó a cabo faloplastia con CLAR y construcción de neouretra tubo-en-tubo, anastomosis microquirúrgica múltiple y recubrimiento del sitio donante con injerto de piel del muslo de espesor parcial. La duración de esta cirugía fue 10 horas y tuvo como complicación crecimiento de vello en la neouretra, que obligó a depilación mecánica endoscópica en repetidas ocasiones. El paciente recuperó sensibilidad peneana, y 18 meses tras la faloplastia se le implantó prótesis Zephyr (Ginebra, Suiza) inflable de un solo cuerpo, utilizando la propia albugínea del cuerpo cavernoso proximal. El paciente se encuentra satisfecho desde el punto de vista cosmético, miccional y sensitivo. Cuatro meses después se encuentra ganando confianza para abordar la penetración. Conclusiones: A pesar del riesgo de complicaciones postoperatorias y de la necesidad de operaciones múltiples, la reconstrucción fálica con CLAR y colocación de implante protésico personalizado puede mejorar el impacto en la función urinaria y sexual secundario a la pérdida del pene

Introduction: The iatrogenic loss of the penis is a rare situation. We present a challenging case of deferred total penile reconstruction in a genetic male. Material and methods: A 57-year-old man with the loss of the penis due to a penile abscess and necrosis secondary to penile curvature surgery. The reconstruction was performed over several operations using a radial forearm free flap (RFFF) and placement of a customised inflatable prosthesis a year later. Results: During the first operation, the penile abscess was drained, the necrotic residues were debrided and placement of hypogastric drainage. Seven weeks later, phalloplasty was performed with RFFF and a tube-in-tube neourethra was constructed. Multiple microsurgical anastomosis was performed, and the donor site was coated with a skin graft from the thigh of partial thickness. The surgery lasted 10 hours and had the complication of hair growth in the neourethra, which required mechanical endoscopic depilation on repeated occasions. The patient regained penile sensitivity. Eighteen months after the phalloplasty, a Zephyr single-body inflatable prosthesis (Geneva, Switzerland) was implanted, using the tunica albuginea of the proximal corpus cavernosum. The patient was satisfied with the aesthetics and urinary and sensory function. Four months later, the patient is gaining confidence to consider penetration. Conclusions: Despite the risk of postoperative complications and the need for multiple operations, phallic reconstruction with RFFF and the placement of a customised prosthetic implant can improve urinary and sexual function secondary to the loss of the penis

Total phallic reconstruction using radial forearm free flap after iatrogenic penile amputation. / Reconstrucción fálica total con colgajo libre antebraquial radial tras amputación peneana iatrogénica.

INTRODUCTION: The iatrogenic loss of the penis is a rare situation. We present a challenging case of deferred total penile reconstruction in a genetic male. MATERIAL AND METHODS: A 57-year-old man with the loss of the penis due to a penile abscess and necrosis secondary to penile curvature surgery. The reconstruction was performed over several operations using a radial forearm free flap (RFFF) and placement of a customised inflatable prosthesis a year later. RESULTS: During the first operation, the penile abscess was drained, the necrotic residues were debrided and placement of hypogastric drainage. Seven weeks later, phalloplasty was performed with RFFF and a tube-in-tube neourethra was constructed. Multiple microsurgical anastomosis was performed, and the donor site was coated with a skin graft from the thigh of partial thickness. The surgery lasted 10hours and had the complication of hair growth in the neourethra, which required mechanical endoscopic depilation on repeated occasions. The patient regained penile sensitivity. Eighteen months after the phalloplasty, a Zephyr single-body inflatable prosthesis (Geneva, Switzerland) was implanted, using the tunica albuginea of the proximal corpus cavernosum. The patient was satisfied with the aesthetics and urinary and sensory function. Four months later, the patient is gaining confidence to consider penetration. CONCLUSIONS: Despite the risk of postoperative complications and the need for multiple operations, phallic reconstruction with RFFF and the placement of a customised prosthetic implant can improve urinary and sexual function secondary to the loss of the penis.

Double autologous lymph node transplantation (ALNT) at the level of the knee and inguinal region for advanced lymphoedema of the lower limb (elephantiasis).

Primary lower-limb lymphoedema is a chronic, progressive and debilitating condition with a difficult management, especially in advanced cases (elephantiasis). Recently, autologous lymph node transplantation (ALNT) appears to be a promising treatment for extremity lymphoedema. A case of a double ALNT for an advanced primary lower-limb lymphoedema is here reported: a contralateral inguinal lymph node flap was transferred to the knee and, in a second surgery, a thoracic lymph node flap was transplanted to the inguinal region. Clinical outcomes at 5 months postoperatively are very satisfactory with reduction in limb circumferences and improvement in skin quality and social impairment.

A phase I, dose-finding study of sunitinib combined with cisplatin and 5-fluorouracil in patients with advanced gastric cancer.

Background This phase I, open-label, dose-escalation study examined the safety, maximum tolerated dose (MTD), and pharmacokinetics of sunitinib plus chemotherapy in patients with advanced gastric cancer. Patients and methods Sunitinib (25 or 37.5 mg/day, Schedule 2/1: 2 weeks on treatment/1 week off) plus chemotherapy (fixed starting doses of cisplatin 80 mg/m(2) and 5-fluorouracil [5-FU] 4,000 mg/m(2)) was administered to patients with advanced gastric cancer who had not received prior therapy for metastatic disease. Results Thirty-four patients were enrolled and received sunitinib 25 mg/day (n = 24) or 37.5 mg/day (n = 10) plus chemotherapy. No dose-limiting toxicity (DLT) was reported in the sunitinib 37.5 mg cohort. However, repeated patterns of myelosuppression beyond the first cycle led to investigation of sunitinib 25 mg/day. This was the MTD, and one DLT (grade 3 mucosal inflammation) was reported. The combination had an acceptable adverse event profile; generally of grade 1/2. There was no evidence of a pharmacokinetic drug-drug interaction between sunitinib and 5-FU. Six patients (26 %) receiving the MTD had a partial response and eight patients experienced stable disease ≥3 months. Conclusions Sunitinib plus cisplatin 80 mg/m(2) and 5-FU 4,000 mg/m(2) were combinable and adverse events were manageable. The MTD of sunitinib was established as 25 mg/day on Schedule 2/1.

Incidence of hand-foot syndrome with capecitabine in combination with chemotherapy as first-linetreatment in patients with advanced and/or metastatic gastric cancer suitable for treatment with a fluoropyrimidine-based regimen

INTRODUCTION: Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy. MATERIALS AND METHODS: This phase II, multicenter, non-controlled study assessed the safety, particularly grade three HFS incidence, and efficacy of four capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for advanced and/or metastatic gastric cancer. RESULTS: One hundred and eight patients were assigned to one of the four treatment groups, according to investigator's criteria, and grouped together for both safety and efficacy primary analyses. HFS was reported in 31 patients (19.6%) and its first presentation occurred at a median of 72 days (range 19-209 days). Grade 3 HFS developed in 6.3, 5.2, 3.7 and 2.4%, of patients receiving ECX, DCX, EOX or CX chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation due to HFS was required in 5.7% of patients (9/158). The most common (> 10%) grade 3-4 treatment-related AEs were neutropenia (15.2%), asthenia (12.0%) and diarrhoea (11.4%). CONCLUSIONS: A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in < 1/3 of patients. The results suggest that capecitabine may be useful in combination with standard fluorouracil-based regimens in patients with advanced and/or metastatic gastric cancer with favourable safety profile (AU)

Consensus of the Spanish Society of Medical Oncology (SEOM) and Spanish Society of Pathology (SEAP) for HER2 testing in gastric carcinoma

The identification of HER2 alterations in advanced gastric carcinomas is of critical importance in daily clinical practice as such neoplasms require specific treatment with trastuzumab. For these reasons, pathologists and oncologists with expertise in gastric carcinomas and HER2 testing from both organisations (SEAP and SEOM) have endeavoured to discuss and agree on national guidelines for HER2 testing in gastric carcinomas. These guidelines are based on the experience of those who participated in the discussions and also on experience published internationally. These agreed guidelines give the minimum requirements that a pathological anatomy laboratory must fulfil in order to guarantee adequate HER2 testing in daily practice. Any laboratories which do not meet the minimum standards set out in the guidelines must make every effort to achieve compliance (AU)

SEOM clinical guidelines for the treatment of pancreatic cancer

Pancreatic cancer (PC) is one of the main causes of cancer-related death in the United States and Europe. Due to its poor long-term survival, all patients with PC should undergo a comprehensive evaluation by a Multidisciplinary Tumor Committee to establish the best therapeutic strategy. Pathologic PC diagnosis should be made according to the latest WHO classification of malignant tumours and an accurate staging is crucial to assess resectability, determine the extension and, in some cases, reestablish biliary flow. For patients with localised resectable disease the standard treatment option is radical pancreatic resection. The aim of resection is to obtain microscopically negative margins (R0) and also to resect the drainage lymph nodes. In those cases diagnosed with locally advanced unresectable or metastatic PC, palliative bypass of intestinal or biliary obstruction followed by chemotherapy or chemoradiation remains the main palliative treatment option. Since 1997, gemcitabine monotherapy has been considered the standard of care for advanced PC. In recent years new chemotherapy combinations and targeted agents have demonstrated significant antitumoral activity, increasing the armamentarium that can be used against this lethal disease (AU)

Phase II study of trastuzumab and cisplatin as first-line therapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer

INTRODUCTION: HER2 over-expression and/or amplification are present in 9-38% of gastric or gastroesophageal junction (GEJ) cancers and are correlated to poor outcome. We conducted a multicentre phase II trial to evaluate trastuzumab in combination with cisplatin in patients with untreated HER2-positive advanced gastric or GEJ cancer. MATERIALS AND METHODS: Chemo-naïve patients with measurable, non-resectable, advanced or metastatic gastric or GEJ adenocarcinoma, with HER2 over-expression and/or amplification (IHC 3+, or IHC 2+ and FISH+), age ≥18 years, ECOG ≤2, left ventricle ejection fraction ≥50% and adequate organ function were eligible. Treatment consisted of trastuzumab (8 mg/kg on cycle 1 day 1 as loading; 6 mg/kg in subsequent cycles) and cisplatin (75 mg/m(2)), both intravenously on day 1, every 21 days. RESULTS: Twenty-two out of 228 patients (10%) were HER2- positive and were included in this phase II trial. The median age was 66 years and ECOG 0/1 was 41%/59%. The median number of cycles was 4 (range 1-41). The confirmed ORR was 32% and disease control was achieved in 64% of patients. Median time to progression was 5.1 months. Grade 3 adverse events included asthenia (27%), neutropenia (18%), anorexia (14%), diarrhoea (9%) and abdominal pain (9%). There were no grade 4 toxicities or treatment-related deaths. Higher baseline HER extracellular domain (ECD) levels were associated with better outcome in terms of response and survival. CONCLUSIONS: Trastuzumab in combination with cisplatin is an active regimen and has a favourable toxicity profile in advanced HER2-positive gastric or gastroesophageal cancers (AU)

Utilización de la toxina botulínica para mejorar la funcionalidad y la expresión del labio en parálisis facial de larga evolución / Use of botulinum toxin to improve the functionality and expression of the lip in long-term facial palsy

La parálisis de la rama marginal del nervio facial en el contexto de una parálisis facial de larga evolución, produce una deformidad estética y funcional que puede ser mejorada con la inyección de toxinabotulínica. Utilizamos esta técnica en 2 pacientes consiguiendo unos resultados casi inmediatos en lo que se refiere a la apertura bucal, a la expresión y a la continenciaoral. Indicamos esta técnica en pacientes de edad avanzada, con múltiples operaciones previas y que aceptan este procedimiento no invasivo para mejorar su autoestima y su calidad de vida (AU)

Paralysis of the marginal branch of the facial nerve in the context of a long-term facial paralysis, produces an esthetic and functional deformity that can be improved with botulinum toxin injection. We use this technique in 2 patients who achievedal most immediate results in terms of oral opening,oral expression and continence. Botulinum toxin injection can be used in elderly patients with multiple previous operations who accept this non-invasive procedure, improving their self esteem and their quality of life (AU)

Biliary cystadenocarcinoma with mesenchymal stroma

Hepatobiliary cystadenocarcinomas (BCACs) with mesenchymal stroma are a rare cystic lesion. This tumour needs to be distinguished from benign biliary cystadenoma, which is antecedent in most cases. The treatment of choice is radical excision of the mass. The diagnostic evaluation, surgical management, pathological characteristics, treatment and follow-up of one patient with hepatobiliary cystadenocarcinoma with ovarian stroma is described. Preoperative diagnosis of BCACs is often difficult, because their clinical manifestations are similar to those of other hepatic cystic lesions. MRI is suitable for accurate characterisation of cystic biliary lesions, but distinguishing between cystadenoma and cystadenocarcinoma remains difficult on the basis of imaging findings. Complete surgical excision gives a relatively good chance of long-term survival because of the slow growth rate of these tumours (AU)

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Weekly docetaxel as second-line therapy for patients with advanced breast cancer resistant to previous anthracycline treatment.

This phase II trial evaluated the efficacy and toxicity of weekly docetaxel as treatment of advanced metastatic breast cancer patients resistant to prior anthracycline chemotherapy. After the first 18 patients, the initial dose (40 mg/m2, 30-min i.v. infusion for 6 consecutive weeks, followed by 2-week rest) was reduced to 36 mg/m2 in the remaining 17 patients due to the incidence of toxicity (28% grade 3-4 asthenia). Overall response rate was 34% (95% CI, 19-50): two complete (6%) and ten partial responses (28%) were found. The median duration of response was 6.8 months, the median time to disease progression was 8.4 months, and the median overall survival was 13.6 months (median follow-up of 11.4 months). Neutropenia was the only severe hematologic toxicity (17% of patients), whereas asthenia, nail, ocular and skin disorders were the most common nonhematologic toxicities. Only one death during further follow-up was related to toxicity (caused by pulmonary fibrosis). In conclusion, we found weekly docetaxel to be an active and safe chemotherapy regimen for patients with metastatic breast resistant to previous anthracyclines. This weekly regimen caused minimal myelosupression, while retaining significant activity against advanced breast cancer. Both factors provide attractive possibilities for the development of combination therapies incorporating weekly docetaxel. Nevertheless, the number of patients receiving either dose (40 and 36 mg/m2) which we studied is low and our results require confirmation on larger groups of patients.

Abordaje laparoscópico en la cirugía radical conservadora del cáncer invasivo de cérvix en pacientes jóvenes. Experiencia preliminar / Laparoscopic approach in radical conservative surgery of invasive cervical cancer in young patients. Preliminary experience

Objetivo: Evaluar, de forma preliminar, la factibilidad de un nuevo enfoque técnico de la cirugía conservadora en pacientes jóvenes afectadas de cáncer cervical invasivo (traquelectomía radical).Sujetos y métodos: Se presentan los primeros 3 casos intervenidos en nuestro centro, correspondientes a pacientes de 35, 36 y 39 años, diagnosticadas de cáncer cervical invasivo en estadio FIGO IB1. Las pacientes fueron informadas del carácter experimental de la técnica, obteniéndose el consentimiento informado detallado. Con objeto de facilitar el abordaje vaginal, la estrategia quirúrgica consistió en realizar un importante esfuerzo de preparación laparoscópica que incluyó, además de la linfadenectomía pélvica, la preparación de los espacios anatómicos y la sección radical de los ligamentos cardinales y uterosacros, preservándose íntegramente la irrigación del cuerpo uterino.Resultados: La fase laparoscópica de la intervención se realizó satisfactoriamente en todos los casos con una duración media de 3 h y 10 min. En los dos primeros casos los exámenes histológicos intraoperatorios permitieron realizar la traquelectomía radical sin incidencias. Ambas piezas quirúrgicas presentaron márgenes libres de tumor, obteniéndose una media de 18 ganglios linfáticos pélvicos. En el tercer caso, el hallazgo intraoperatorio de una metástasis ganglionar obligó a completar la histerectomía radical por vía vaginal.Se registraron dos complicaciones postoperatorias: un absceso de Douglas que requirió drenaje mediante culdocentesis y una hernia incisional de epiplón que requirió reparación quirúrgica.Actualmente, las dos pacientes tratadas de forma conservadora realizan un tratamiento anticonceptivo oral presentando menstruaciones regulares y citologías seriadas negativas.Conclusiones: Hemos observado que la preparación laparoscópica, incluyendo la sección de los ligamentos cardinales y uterosacros, permite conservar la irrigación del cuerpo uterino y facilita la cirugía radical por vía vaginal (AU)

High-dose mitoxantrone and cyclophosphamide without stem cell support in high-risk and advanced solid tumors: a phase I trial.

This phase I study was designed to develop a high-dose combination of two cycles of mitoxantrone and cyclophosphamide in patients with solid tumors, as an alternative to single-cycle high-dose regimens that use only alkylating agents. Treatment was delivered with granulocyte colony-stimulating factor (G-CSF), but without stem cell support, in order to avoid potential tumor cell reinfusion. Thirty-one patients with advanced solid tumors received two cycles of high-dose mitoxantrone (20-30 mg/m2) plus high-dose cyclophosphamide (3000-4000 mg/m2). All patients received G-CSF until hematologic recovery. Dose-escalation was performed when less than 50% of cycles per level had dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) achieved was mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2. Main dose-limiting toxicities (DLTs) were hematological: grade IV neutropenia lasting more than 7 days and thrombopenia below 20 x 10(9)/l requiring more than one platelet transfusion. Non-hematological DLT consisted predominantly of grade III emesis and asthenia. Follow-up after each cycle was performed in an outpatient setting and there were no toxic deaths. In conclusion, the administration of two cycles of high-dose mitoxantrone and cyclophosphamide with G-CSF support is safe and feasible. MTD was mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2. Evaluation of this regimen is being done in a phase II trial.

Rifampin does not improve the efficacy of quinolone antibacterial prophylaxis in neutropenic cancer patients: results of a randomized clinical trial.

PURPOSE: To determine whether the addition of rifampin to a quinolone-based antibacterial prophylactic regimen in patients undergoing high-dose chemotherapy (HDC) with peripheral-blood stem-cell transplantation (PBSCT) decreases the incidence of neutropenia and fever, Gram-positive bacteremia, and infection-related morbidity. PATIENTS AND METHODS: Patients with solid tumors undergoing HDC with PBSCT were randomized to receive prophylactic antibiotics with either ciprofloxacin 500 mg orally every 8 hours or the same ciprofloxacin regimen with rifampin 300 mg orally every 12 hours. Prophylaxis was started 48 hours before stem-cell reinfusion. Patients were monitored to document the occurrence of neutropenia and fever, incidence and cause of bacterial infection, time to onset and duration of fever, requirement for intravenous antimicrobials, and length of hospital admission. RESULTS: Sixty-five patients were randomized to receive ciprofloxacin and 65 to receive ciprofloxacin plus rifampin, and from these groups, 62 and 61 were assessable, respectively. The proportion of patients who developed neutropenia and fever was 87% in the group treated with ciprofloxacin and 78% in the group treated with ciprofloxacin and rifampin (P =.25). Although there was a trend toward a reduction in the overall incidence of bacteremia (12 v 4 patients), and Gram-positive bacteremia (8 v 2 patients) with the addition of rifampin, none of these comparisons was statistically significant (P =.05 and P =.09, respectively). CONCLUSION: The results of this study, which demonstrate that rifampin does not improve ciprofloxacin antibacterial prophylaxis in cancer patients undergoing HDC with PBSCT support but that it does increase the occurrence of undesirable side effects, do not support the routine use of rifampin in this setting.

A phase II study of a novel gemcitabine plus cisplatin regimen administered every three weeks for advanced non-small-cell lung cancer.

BACKGROUND: The aim of this study was to determine the clinical activity and toxicity of a novel chemotherapy combination regimen of gemcitabine plus cisplatin, administered every three weeks, in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-six previously untreated stages III (14) and IV (12) patients were included. Gemcitabine was administered on days 1 and 8 at a dose of 1250 mg/m2 and cisplatin was administered at a dose of 100 mg/m2 on day 1, every 21 days. RESULTS: Twenty-five patients were evaluable for response. One patient achieved a complete response, and 16 patients partial responses. The overall response rate was 65.3% (95% CI: 45%-82%). The main toxicity was hematological: neutropenia NCIC-CTC grade 3-4 in 54% of the patients, and thrombocytopenia grade 3-4 in 23%. The non-hematological toxicity was mild and tolerable. Only 13% of gemcitabine injections were dose-reduced or omitted due to toxicity. The actual dose-intensity of gemcitabine was 715 mg/m2/week, and 31 mg/m2/week for cisplatin. These figures represent the 86% and 93% of the theoretical dose intensity of both drugs, respectively. With a median follow-up of 10 months (range 7-13), 17 patients are still alive and nine have died. The median overall survival is 12 months. CONCLUSION: This novel combination of gemcitabine and cisplatin administered every three weeks is well tolerated and induces a remarkably high response rate. The regimen proves more interesting than the four-week schedules, particularly regarding patients who are candidates for local therapy.