This phase I trial evaluated the combination of oxaliplatin plus UFT in patients with advanced solid tumors to determine the maximum tolerated dose (MTD) and the dose limiting-toxicity for future ...phase II trials. Eligible patients (N = 27) were treated in sequential cohorts of three to six patients. The starting doses for oxaliplatin and UFT were 70 mg/m2 and 250 mg/m2/day respectively, and five dose levels were designed up to 85 mg/m2 and 400 mg/m2/day. Oxaliplatin was administered i.v. on day 1 and 15, and oral UFT was given daily in three divided doses on days 1-21 followed by 1 week rest of a 28-day cycle. At the recommended dose, six additional patients were entered. In total, 79 courses were administered with a median of 3 (range 1-6). MTD was not reached; oxaliplatin 85 mg/m2 on day 1 and 15 plus UFT 400 mg/m2/day for 21 days was considered the optimum combination for phase II trials. Gastrointestinal toxicity and asthenia were the most common adverse events. Eight out of 13 patients (61.5%) with metastatic colorectal cancer achieved stable disease. UFT plus oxaliplatin is a feasible and safe combination. A phase II trial in first-line advanced colorectal cancer is ongoing.
Severe tricuspid regurgitation (TR) secondary to interference pacemaker (PM) cable is a rare cause of progressive right heart failure (HF), which can worsen patient outcomes.
We present 3 clinical ...cases of right HF secondary to TR after PM implantation.
In these patients the clinic is right HF, which can appear early, as in our second patient, or after years of implementation of the PM, as in the first and third patients. The diagnosis is confirmed by echocardiography, the most accurate 3D, followed by transesophageal. The 2D transthoracic can not detect it, because it has low sensitivity for TR associated with PM. Medical treatment is always the first choice, since any other procedure carries significant morbidity and mortality.
Probably this is a condition that we will diagnose with increasing frequency, because there are more and more patients with devices and, at the same time, the diagnostic tools are improving.
Background
Biologicals, in combination with chemotherapy, are recommended as first-line treatment of metastatic colorectal cancer (mCRC); however, evidence guiding the appropriate management of older ...patients with mCRC is limited.
Objective
This study was undertaken to compare the efficacy and safety outcomes in older versus younger patients with mCRC who received first-line biological therapy.
Methods
This retrospective analysis used pooled data from five trials undertaken by the Spanish Cooperative Group for the Treatment of Digestive Tumours. All were studies of adults with advanced CRC who received first-line treatment with chemotherapy plus bevacizumab, cetuximab or panitumumab, stratified by age (≥ 65 vs. < 65 years). Endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and safety.
Results
In total, 999 patients from five studies were included in the analysis: 480 (48%) were aged ≥ 65 years, and 519 (52%) were aged < 65 years. Median PFS did not differ significantly between patients aged ≥ 65 and < 65 years (9.9 vs. 9.4 months; hazard ratio HR 1.01; 95% confidence interval CI 0.88–1.17). Median OS was significantly shorter in older than in younger patients (21.3 vs. 25.0 months; HR 1.21; 95% CI 1.04–1.41). There was no significant difference between older and younger patients in ORR (59 vs. 62%). Patients aged ≥ 65 years experienced significantly more treatment-related grade 3 or higher adverse events (61.67%) than did patients aged < 65 years (45.86%).
Conclusions
Biologicals plus chemotherapy is an effective first-line treatment option for selected patients aged ≥ 65 years with mCRC and has a manageable safety profile and efficacy comparable to that observed in younger patients.
Severe tricuspid regurgitation (TR) secondary to interference pacemaker (PM) cable is a rare cause of progressive right heart failure (HF), which can worsen patient outcomes.
We present 3 clinical ...cases of right HF secondary to TR after PM implantation.
In these patients the clinic is right HF, which can appear early, as in our second patient, or after years of implementation of the PM, as in the first and third patients. The diagnosis is confirmed by echocardiography, the most accurate 3D, followed by transesophageal. The 2D transthoracic cannot detect it, because it has low sensitivity for TR associated with PM. Medical treatment is always the first choice, since any other procedure carries significant morbidity and mortality.
Probably this is a condition that we will diagnose with increasing frequency, because there are more and more patients with devices and, at the same time, the diagnostic tools are improving.
La insuficiencia tricuspídea (IT) grave secundaria a interferencia del cable del marcapasos (MCP) es una causa infrecuente de insuficiencia cardiaca (IC) derecha progresiva, que puede complicar la evolución del paciente.
Presentamos 3 casos clínicos de IC derecha secundaria a IT tras implantación de MCP.
En estos pacientes la clínica consiste en IC derecha, que puede aparecer de forma precoz, como en nuestra segunda paciente, o al cabo de años de la implantación del MCP, como en el primer y la tercera pacientes. El diagnóstico se confirma por ecocardiografía, siendo la más precisa la 3D, seguida de la transesofágica. La 2D transtorácica puede no detectarla, ya que tiene baja sensibilidad para la IT asociada a MCP. El tratamiento médico es siempre la primera opción, ya que cualquier otro procedimiento conlleva una morbimortalidad significativa.
Probablemente, esta es una patología que vamos a diagnosticar cada vez con más frecuencia, ya que cada vez hay más pacientes con dispositivos y, al mismo tiempo, están mejorando las herramientas diagnósticas.
Purpose
A multicenter phase I trial to establish the recommended dose of CPT-11/docetaxel plus cisplatin in advanced esophagogastric cancer patients and to correlate the efficacy and toxicity with ...genetic polymorphisms in DNA repair genes (XPD and XRCC3) and the UGT1A1 gene.
Methods
Four dose levels with a fixed dose of cisplatin (60 mg/m
2
), day 1, and dose-escalation of CPT-11 (50–70 mg/m
2
) and docetaxel (25–30 mg/m
2
), days 1 and 8, every 3 weeks were planned. Polymorphisms of XPD (Asp312Asn and Lys751Gln), XRCC3 (Thr241Met) and UGT1A1*28 were examined in baseline peripheral blood.
Results
Twenty-eight patients were included at three different dose levels. Dose-limiting toxicities were febrile neutropenia and diarrhea; the recommended dose was established at CPT-11 60 mg/m
2
and docetaxel 25 mg/m
2
plus cisplatin 60 mg/m
2
. Objective response was observed in 13 patients (50%). Median time to progression was 6.6 months, and median survival was 11.3 months. Median time to progression was 9.7 months for patients harboring the XRCC3 Met241Met genotype versus 8.4 months for patients with Thr241Met and 3.1 months for those with Thr241Thr (
P
= .04).
Conclusions
CPT-11/docetaxel plus cisplatin is active in patients with advanced esophagogastric cancer. XRCC3 Met241Thr polymorphisms could be a useful marker to predict prognosis in patients treated with a cisplatin-based chemotherapy. However, these results are required to be confirmed with a great number of patients.
Oxaliplatin (L-OHP), irinotecan (CPT-11) and 5-fluorouracil (5-FU) have shown their efficacy in metastatic colorectal cancer. The synergism of these drugs has been demonstrated in vivo and in vitro. ...The aim of this study was to determine the recommended dose of the triple combination of L-OHP, CPT-11 and CI 5-FU for a further phase II study. Eighteen patients received the study treatment in four dose levels. The male:female ratio was 15:3 and the median age was 51.6 years (range 30-71). The type of tumor was colon in eight patients, rectum in four and other locations in six patients. The treatment was repeated every 2 weeks, at the fixed dose of L-OHP, 85 mg/m, and escalated doses of CPT-11 and 48-h infusion 5-FU of 100/2000, 100/2250, 125/2250 and 150/2250 mg/m. Only one previous treatment for the advanced disease was permitted. Patients received a median of 8 cycles (range 1-26) and a total of 152 cycles were administered. Dose intensity administered at dose level L-OHP 85 mg/m, CPT-11 150 mg/m and 5-FU 2250 mg/m was 95, 92 and 95% for L-OHP, CPT-11 and 5-FU, respectively. One patient in level 2 and one patient in level 4 presented dose-limiting toxicity that was not confirmed in the three required additional patients by level. The anti-tumor activity was assessed in nine patients: seven partial responses, one stable disease and one progressive disease. The maximum-tolerated dose was not reached, and thus the recommended dose for this combination schedule is L-OHP, 85 mg/m, CPT-11, 150 mg/m and 5-FU, 2250 mg/m 48-h continuous infusion, the same doses that were recommended for the drugs when administered in combination therapy of L-OHP + 5-FU or CPT-11 + 5-FU. A phase II study in first-line treatment of patients with metastatic colorectal cancer with this dose regimen is ongoing.
Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as ...a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032).
BackgroundPopulation distribution of reduced diffusing capacity of the lungs for carbon monoxide (DLCO) in smokers and main consequences are not properly recognised. The objectives of this study were ...to describe the prevalence of reduced DLCO in a population-based sample of current and former smoker subjects without airflow limitation and to describe its morphological, functional and clinical implications.MethodsA sample of 405 subjects aged 40 years or older with postbronchodilator forced expiratory volume in 1 s/forced vital capacity (FVC) >0.70 was obtained from a random population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, exhaled carbon monoxide (CO) measurement, spirometry, DLCO determination, 6 min walk test, routine blood analysis and low-dose CT scan with evaluation of lung density and airway wall thickness.ResultsIn never, former and current smokers, prevalence of reduced DLCO was 6.7%, 14.4% and 26.7%, respectively. Current and former smokers with reduced DLCO without airflow limitation were younger than the subjects with normal DLCO, and they had greater levels of dyspnoea and exhaled CO, greater pulmonary artery diameter and lower spirometric parameters, 6 min walk distance, daily physical activity and plasma albumin levels (all p<0.05), with no significant differences in other chronic respiratory symptoms or CT findings. FVC and exhaled CO were identified as independent risk factors for low DLCO.ConclusionReduced DLCO is a frequent disorder among smokers without airflow limitation, associated with decreased exercise capacity and with CT findings suggesting that it may be a marker of smoking-induced early vascular damage.Trial registration numberNCT03028207.
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