169,867 research outputs found
Targeted therapy for renal cell carcinoma: Focus on 2nd and 3rd line
No full textntroduction: Second- and third-line treatments are more and more frequently administered to metastatic renal cell carcinoma (mRCC) patients. Areas covered: Here we discuss the various levels of evidence supporting presently available recommendations, trying to address a number of as yet unanswered issues, and also to take a glowing glance at the future. To do this, we interrogated the Medline database, as well as the proceedings of the main Oncological and Urological conferences for relevant studies. Expert opinion: Until recently, with regard to choosing the second line treatment after the failure of therapy with vascular endothelial growth factor receptors-tyrosine kinase inhibitors (VEGFR-TKIs), the continued inhibition of the VEGF/VEGR pathway, or else the switch to an mTOR inhibitor, is recommended. These two options are characterized by partly different targets, completely different toxicity profiles, but a comparable efficacy. This scenario will change soon, after the publication of two randomized, controlled, phase III trials in which cabozantinib and nivolumab proved to be superior as compared to everolimus. As regards third line treatment, where a sequence of two VEGFR-TKIs has been used beforehand, the choice is represented by the mTOR inhibitor everolimus, whilst if a VEGFR-TKI followed by everolimus has been chosen, a return to VEGF pathway inhibition is suggested
Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma
No full textRibonucleases are a superfamily of enzymes which operate at the crossroads of transcription and translation, catalyzing the degradation of RNA; they can be cytotoxic because the cleavage of RNA renders indecipherable its information. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA, thus leading to inhibition of protein synthesis and, ultimately, to cytostasis and cytotoxicity. Ranpirnase has demonstrated antitumor activity both in vitro and in vivo in several tumor models. The maximum tolerated dose emerging from phase I studies was 960 g/m2, with renal toxicity as the main dose-limiting toxicity. A large phase II trial showed that ranpirnase has disease-modifying activity against malignant mesothelioma. Ranpirnase proved to be superior to doxorubicin in a phase III trial, while preliminary results of another large, phase III trial, suggest that the combination of ranpirnase and doxorubicin could be more effective than doxorubicin alone. In all the above studies, ranpirnase seems to act mainly as a cytostatic rather than a cytotoxic drug, stabilizing progressive disease and potentially prolonging patients' survival. Ranpirnase may thus find its niche in combination with doxorubicin for mesothelioma as a second-line therapy, where no standard of care presently exists. © 2008 Dove Medical Press Limited. All rights reserved
Slow and steady wins the race: practical (and philosophical) considerations of treatment activity evaluation when novel anticancer agents just slow neoplastic progression.
No full text
Dovitinib (CHIR258, TKI258): Structure, development and preclinical and clinical activity
No full textDovitinib is an oral multikinase inhibitor targeting FGF receptors, PDGF receptors and VEGF receptors. Its activity against FGF receptors suggests its usefulness in treating cancers after the failure of VEGF/VEGF receptor-targeting agents. The identified dose and schedule to be used in further studies was 500 mg orally for 5 days on and 2 days off. Biological considerations and the results achieved in a Phase I/II trial suggested its activity in advanced renal cell carcinoma patients pretreated with a tyrosine kinase inhibitor and an mTOR inhibitor. Surprisingly, in a randomized controlled Phase III trial versus sorafenib in the same setting, dovitinib failed to demonstrate any superiority. At present, dovitinib is being tested in different tumor types. However, molecular-based patient selection seems to be key to fully exploit the activity of this drug
The natural history of asymptomatic ventricular preexcitation in children. A long-term electrophysiologic-based follow-up study for risk stratification
No full textC-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as inflammation markers in elderly patients with stable chronic obstructive pulmonary disease (COPD)
No full textErythrocyte sedimentation rate (ESR) might represent a less expensive alternative to C-reactive protein (CRP) as a marker of systemic inflammation in stable chronic obstructive pulmonary disease (COPD). We tried to verify this hypothesis in 223 consecutive outpatients aged 65 years or more with stable COPD enrolled in a multicenter observational study. Patients were grouped according to normal/increased ESR/CRP values and groups were compared with regard to clinical and laboratory characteristics. Correlations between CRP, ESR and selected variables of interest were assessed by Spearman's zeta-test and multivariate linear regression analysis. CRP was weakly and inversely correlated with the forced expiratory volume in the first second (FEV1%) (Spearman's zeta=-0.15; p<0.027), while ESR was not (Spearman's zeta=-0.05; p=0.411). The highest prevalence of anemia and hypoalbuminemia and the lowest FEV1% were recorded in high ESR-high CRP group. For anemia B=14.180+/-3.521 (+/-S.E.M.); p=0.001 and hypoalbuminemia B=10.241+/-3.790; p=0.007 qualified as significant independent correlates of ESR values, while only FEV1 remained significantly associated with CRP values (B=-0.570+/-0.258; p=0.028). In conclusion, CRP, but not ESR, shows a weak correlation with COPD severity, while anemia and hypoalbuminemia are main correlates of high ESR. Neither ESR, nor CRP qualify as reliable markers of COPD severity and seem to reflect the effects of different determinants
Recording Risk Factors of Physical Abuse in Children Younger Than 36 Months With Bone Fractures: A 12-Years Retrospective Study in an Italian General Hospital Emergency Room
No full textSkeletal fractures (SFs) are very common in pediatrics. In some cases, they are secondary to child abuse. Differentiation of accidental from non-accidental fractures (NAFs) is essential as in abused children risk of further injuries leading to severe clinical problems and death is significant. Main objectives of this study were to evaluate the characteristics of SFs of children ≤3 years of age presenting to the Emergency Room (ER) of a Children's Teaching Hospital over a 12-year period and the attention paid by ER physicians to the identification of the indicators that increase suspicion of NAF and that suggest referring of the patient to the child protection agencies. This is a descriptive, retrospective study of the medical records of all the pediatric patients ≤ 36 months of age admitted to the ER of the Azienda Ospedaliera Santa Maria della Misericordia, University of Perugia, Perugia, Italy, for radiological documented SFs between January 1, 2004, and March 31, 2016. Available information was used to evaluate whether indicators of possible child abuse were documented by the ER staff and whether diagnosis of potential abuse was followed by further screening or referral to child protection agencies. During the study period, 11,136 accesses of the ER by children younger than 36 months were documented, among whom 417 presented long bone or skull fractures. Skull fractures were significantly more common among children <12 months of age (p = 0.001), whereas radius/ulna and humerus fractures were diagnosed significantly more frequently in children 12–36 months of age (p = 0.036 and p = 0.022, respectively). Recorded medical history was considered inadequate in 255 (61.2%) cases with no difference related to patient's age. Our study showed that the majority of charts in case of SFs were found to contain inadequate documentation to explain causes at the heart of the fractures and, therefore, to rule out any inflicted trauma. The development of specific referral guidelines, along with the continuous education and training of health professionals, as well as the preparation of structured medical forms, are essential measures to activate in order to improve the referral of children from the ER to child protection agencies
Evaluation approach for a combined implementation of day 1 C-ITS and truck platooning
No full textWith the advance of automation in the field of transportation, the number of emerging systems that are going to be deployed on the European roads is growing fast. The aim of C-Roads Italy, part of the Europe-wide C-Roads Project, is to evaluate the impacts on public roads and the feasible operational modes of Truck Platooning, when jointly implemented with Day 1 C-ITS. This paper, first, reports an extended summary of the available bibliography on Truck Platooning focused on the assessment of the implementation scenario presented as an example in Section IV. The literature review is necessary to investigate the more promising implementation schemes in the short term on the European area and the system expected impacts when deployed as a stand-alone service. Then, the evaluation methodology that is currently being drafted in the activity of C-Roads Italy is described, aimed to assess the jointed impact of Day 1 C-ITS services and Truck Platooning. Finally, a meaningful example of the approach for the evaluation of the jointed implementation of Truck Platooning and C-ITS services is presented, considering one of the use cases of the Road Works Warning Service, as defined in the current version of the C-Roads documents
Sunitinib in advanced metastatic non-clear cell renal cell carcinoma: a single institution retrospective study.
No full textAIM:
Sunitinib is an orally active multi-targeted tyrosine kinase inhibitor that exerts its antitumor effects primarily through the selective inhibition of VEGF. Novel targeted therapies such as sunitinib have transformed the treatment of advanced metastatic renal cell carcinomas, particularly those with clear cell histology. Here, our experience in patients with non-clear cell kidney cancer treated as part of the sunitinib Expanded Access Program is reported.
MATERIALS & METHODS:
This was a retrospective assessment of 21 patients with non-clear cell renal cell carcinoma who were treated with oral sunitinib 50 mg/day in repeated 6 weekly cycles (4 weeks on and 2 weeks off). Disease assessment and physical examination were recorded at baseline and tumor assessments were performed every 3 months, according to Response Evaluation Criteria In Solid Tumors. The primary outcome measure was progression-free survival.
RESULTS:
Patients received an average of 6.38 cycles of sunitinib; one patient was classified as a complete responder and two as partial responders. The overall response rate was 14.3% and clinical benefit was attained by 52.4%. The median progression-free survival was 4.1 months while median overall survival was 14.6 months. In general, sunitinib was well tolerated and only three patients experienced a grade 3 toxicity, which resolved with dosage reduction.
CONCLUSION:
As expected, sunitinib exerted lower antitumor activity in patients with non-clear cell renal cell carcinoma than was achieved in the general population with metastatic kidney cancer. However, responses (one complete and two partial) were documented and clinical benefit was observed in more than half of all patients
- …
