1,721,002 research outputs found
Current achievements and future perspectives of metronomic chemotherapy
No full textIn recent years, many anticancer drugs have been tested at metronomic dosages for a variety of tumours. Mechanisms of action attributed to metronomic chemotherapy (MCT) include antiangiogenesis, immunomodulation, direct inhibition of tumour growth, effect on tumour initiating cells and the modulation of clonal evolution. An active clinical research, aimed at testing MCT in several cancers, has been conducted over the past 15 years. However, because the majority of available results come from earlier phase II studies, mainly performed in the area of breast cancer (BC), it is clear that there are areas still to be investigated. We considered current studies dealing with MCT according to the clinical setting of patients. Despite a certain degree of overlap, we were able to identify four main clinical indications for MCT: refractory disease and frailty of patients, advanced stage disease (requiring first and second-line therapy), early stage disease and maintenance therapy after induction chemotherapy. In addition, a section of this review has been addressed to the combination of MCT with immunotherapy following the growing interest in the reinstatement of immune-surveillance. Crucial questions, such as the definition of optimal schedules of continuously delivered, low-dose chemotherapy and the recognition and validation of predictive biomarkers, need to be further addressed. Moreover, comparisons with the best supportive care are especially lacking and thus urgently awaited to establish the key role of MCT in the care of pretreated and frail patients. Maintenance therapy promises to be one of the most worthwhile developments for MCT. Currently, several combination strategies with standard chemotherapy, target agents or immunotherapy are under investigation but further efforts are needed to fill the gaps of knowledge in this field
Tackling pancreatic cancer with metronomic chemotherapy
No full textPancreatic tumours, the majority of which arise from the exocrine pancreas, have recently shown an increasing incidence in western countries. Over the past few years more and more new selective molecules directed against specific cellular targets have become available for cancer therapy, leading to significant improvements. However, despite such advances in therapy, prognosis of pancreatic cancer remains disappointing. Metronomic chemotherapy (MCT), which consists in the administration of continuous, low-dose anticancer drugs, has demonstrated the ability to suppress tumour growth. Thus, it may provide an additional therapeutic opportunity for counteracting the progression of the tumour. Here we discuss evidence arising from preclinical and clinical studies regarding the use of MCT in pancreatic cancer. Good results have generally been achieved in preclinical studies, particularly when MCT was combined with standard dose chemotherapy or antinflammatory, antiangiogenic and immunostimolatory agents. The few available clinical experiences, which mainly refer to retrospective data, have reported good tolerability though mild activity of metronomic schedules. Further studies are therefore awaited to confirm both preclinical findings and the preliminary clinical data
Association Between Proton Pump Inhibitors and Metronomic Capecitabine as Salvage Treatment for Patients With Advanced Gastrointestinal Tumors: A Randomized Phase II Trial
No full textMetronomic chemotherapy for cancer treatment: A decade of clinical studies
No full textPurpose: Over the past few years, more and more new selective molecules directed against specific cellular targets have become available for cancer therapy, leading to impressive improvements. In this evolving scenario, a new way of delivering older cytotoxic drugs has also been developing. Many studies demonstrated that several cytotoxic drugs have antiangiogenic properties if administered frequently and at lower doses compared with standard schedules containing maximal tolerated doses (MTD). Such a new strategy, named metronomic chemotherapy, focuses on a different target: the slowly proliferating tumour endothelial cells. About 10 years ago, metronomic chemotherapy was firstly enunciated and hereafter many clinical experiences were published related to almost any cancer disease. This review analyses available studies dealing with metronomic chemotherapy and its combination with several targeted agents in solid tumours. Methods: A computerized literature search of MEDLINE was performed using the following search terms: metronomic OR "continuous low dose" AND chemotherapy AND cancer OR solid tumours. Results: Satisfactory results have been achieved in diverse tumour types, such as breast and prostate cancer or paediatric sarcomas. Moreover, many studies have reported that metronomic chemotherapy determined minimal toxicity compared to MTD chemotherapy. Overall, published series on metronomic schedules are very heterogeneous often reporting on retrospective data, while only very few studies were randomized trials. These limitations still prevent to draw definitive conclusions in diverse tumour types. Conclusions: Large well-designed studies are eagerly awaited for confirming the promises of metronomic schedules and their combinations with targeted molecules. © 2013 Springer-Verlag Berlin Heidelberg
Recent advances for the treatment of pancreatic and biliary tract cancer after first-line treatment failure
No full textpeer reviewe
Evolving treatments for advanced gastric cancer: appraisal of the survival trend
No full textWe analysed the results of the main clinical studies looking at patients with advanced gastric or esophagogastric junction cancer, in order to differentiate between what is already clinical evidence and what is a promise for the cure of such patients. Thus, achievements from key studies, which had been purposely directed at chemotherapy, molecular target therapies and immunotherapy in both first and second-line setting were analysed. Metronomic chemotherapy, which consists of the administration of continuative low-dose anticancer drugs, was considered also. It was found that patients included in experimental arms of randomized trials compared with controls have often benefited from a statistically significant extension of overall survival. However, further studies are awaited to bring new drugs into clinical practice and to validate candidate biomarkers predictive of response
Duodenobronchial fistula arising from a necrotizing liver metastasis of right colon cancer after systemic chemotherapy
No full text[No abstract available
Tailored Angiogenesis Inhibition in Cancer Therapy: Respecting the Heart to Improve the Net Outcome
No full textEven though cancer therapies attain nowadays as many as 10 million survivors, some studies surprisingly report a higher risk of cardiovascular death compared with that of tumor recurrence. Cancer survivors are thus candidates for a thorough cardiovascular evaluation, because they acquire cardiovascular risk together with oncologic cure. VEGF or tyrosinkinase inhibitors, increasingly used in a large variety of tumours with a significant survival advantage, are prototypical drugs simultaneously realizing oncologic care and cardiotoxicity, by targeting angiogenic replicative pathways, involved in both cardiac health and cancer progression. The pathophysiology of cardiovascular disease, mainly consisting in defective angiogenesis, is indeed opposite to that of tumorigenesis and metastasis spreading, both crucially sustained by enhanced blood vessel development. The clinical expression of cardiotoxicity includes not only the development of a dilated hypokinetic cardiomyopathy, currently generally treated with cardiological drugs, but also hypertension, clinical or subclinical atherothrombotic ischemic heart disease and ischemic cardiomyopathy. These clinical syndromes deserve a more adequate cardiovascular assessment and appropriate advanced treatment strategies including percutaneous coronary intervention, coronary artery bypass graft, or device implantation. If not proactively suspected, diagnosed and treated, these manifestations may lead to cardiac events, and reduce overall survival. This review analyzes the available evidence about molecular pathways, predictors and monitoring of impaired angiogenesis-driven cardiotoxicity. Even clinical relevance, pharmacodynamics and markers of efficacy of various intended or "accidental" antiangiogenic drugs will be discussed with the purpose of easing appropriate cardiological surveillance and treatment. Drug tailoring aimed at outcome and cost-effectiveness, according to both drug susceptibility and cardiovascular vulnerability will be finally revised. © 2012 Bentham Science Publishers
Duodenobronchial fistula arising from a necrotizing liver metastasis of right colon cancer after systemic chemotherapy
No full text[No abstract available
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