159 research outputs found
Cetuximab: still an option in the treatment of pancreatic cancer? Expert Opin Biol Ther. 2013 May;13(5):791-801
No full textPalliative treatment
No full textAlthough there has been a slow but steady decrease in incidence, gastric cancer remains the second leading cause of cancer death worldwide. Several aspects of the oncological and surgical management are still controversial and so gastric cancer represents a challenge for the surgeon. This book aims to delineate the state of the art in the surgical and oncological treatment of gastric cancer, describing the new TNM staging system, the extent of visceral resection and lymphadenectomy focusing on the different open and minimally invasive surgical techniques and discussing intraoperative chemohyperthermia and neoadjuvant and adjuvant treatment. Operative endoscopy and endoscopic ultrasonography are also discussed, as these now have an important role in both diagnostic work-up and palliative care of gastric cancer patients. Only a multidisciplinary approach involving the surgeon, gastroenterologist, and oncologist can produce the comprehensive and integrated overview that today constitutes a winning strategy for the optimization of results.What we hope we have achieved is a flexible, up-to-date, exhaustive publication, rich in illustrations and consistent with evidence-based medicin
Selecting the best treatment for an individual patient.
No full textSeveral factors concur in determining outcome for locally advanced gastric cancer patients. Shockingly, geographic origin of the patient seems to play a major role. In Eastern countries, the high level of surgery that can be expected grants a high percentage of success in a strategy that employs surgery as immediate treatment followed by adjuvant chemotherapy, mainly based on oral fluoropyrimidines (S-1 or Capecitabine), with satisfactory results. In Western countries, the expertise of the surgeon maintains its role as predictor of high likelihood of cure. Indeed, patients treated with standard D2 lymph node dissection have a significantly better survival than those who do not obtain the same kind of treatment. For patients who underwent a suboptimal resection (less than a D1) the classical indication is for a combined adjuvant chemoradiotherapy. In patients who obtain a good surgical outcome, the benefit of the addition of adjuvant chemotherapy is still debatable: the gain in survival seems to be small (around 8 \% at 5 years) and with noticeable toxicities (usually with dismal compliance for patients treated). On this basis, neoadjuvant treatment is a promising option even if there is a general lack of conclusive data regarding which is the best regimen to use. Even with the limitation of a small number of studies (with difficulties in enrollment), neoadjuvant chemotherapy is usually feasible, allows for a greater chance of receiving chemotherapy at all, and opens the possibility of a downstaging and downsizing of the tumor, allowing an easier surgery. Regarding this strategy preliminary results have also been presented about the addition of monoclonal antibodies. For example, in the TOGA trial, a significant benefit in terms of overall survival, response rate, and progression free survival was observed also for patients with locally advanced gastric cancer and not just for the metastatic ones. In the AVAGAST trial also, the addition of Bevacizumab failed to determine a significant improvement in the primary outcome, overall survival, for patients treated with the combination, but in the subgroup analysis, patients with locally advanced gastric cancer had a significantly better overall survival and response rate. This data was the basis for the newest neoadjuvant trial, of Cunningham et al., the MAGIC2 trial, with the peri-operative use of ECX+Bevacizumab. Finally, an increasing interest in the use of hyperthermic intraperitoneal chemotherapy in other types of solid tumors (including those of the gastrointestinal tract such as colon cancer) has led to evaluate this treatment modality in gastric cancer patients with peritoneal involvement. It should be noted that it is still to be considered an experimental approach, even though it would be intriguing to evaluate if a particular subset of patients, those who are more likely to develop peritoneal metastasis, may benefit from this technique in the adjuvant setting. It should be considered that other than histologic subtype (diffuse vs intestinal) there seems to be a series of polymorphisms of genes usually involved in cell interaction and migration that can explain a different metastatic pattern in resected patients. Further research on these determinants of metastatic spread could be used to select those patients who may benefit from HIPEC and those who may benefit from standard adjuvant or that gain no benefit at all
Early onset of hypertension and serum electrolyte changes as potential predictive factors of activity in advanced hcc patients treated with sorafenib: Results from a retrospective analysis of the HCC-AVR group
No full textHypertension (HTN) is frequently associated with the use of angiogenesis inhibitors targeting the vascular endothelial growth factor pathway and appears to be a generalized effect of this class of agent. We investigated the phenomenon in 61 patients with advanced hepatocellular carcinoma (HCC) receiving sorafenib. Blood pressure and plasma electrolytes were measured on days 1 and 15 of the treatment. Patients with sorafenib-induced HTN had a better outcome than those without HTN (disease control rate: 63.4% vs. 17.2% (p=0.001); progression-free survival 6.0 months (95% CI 3.2-10.1) vs. 2.5 months (95% CI 1.9-2.6) (p<0.001) and overall survival 14.6 months (95% CI9.7-19.0) vs. 3.9 months (95% CI 3.1-8.7) (p=0.003). Sodium levels were generally higher on day 15 than at baseline (+2.38, p<0.0001) in the group of responders (+4.95, p <0.0001) compared to patients who progressed (PD) (+0.28, p=0.607). In contrast, potassium was lower on day 14 (-0.30, p=0.0008) in the responder group (-0.58, p=0.003) than in those with progressive disease (-0.06, p=0.500). The early onset of hypertension is associated with improved clinical outcome in HCC patients treated with sorafenib. Our data are suggestive of an activation of the renin-angiotensin system in patients with advanced disease who developed HTN during sorafenib treatment
The Tower of Babel of liver metastases from colorectal cancer: Are we ready for one language?
No full textAdvances in surgical and medical treatments have significantly changed the management of colorectal cancer liver metastases (CRCLMs). In particular, new drugs and modern combination chemotherapy regimens, together with the improvement of surgical techniques, allow a potentially curative approach in an increasing number of patients. Nevertheless, there is no strong evidence for an optimal treatment strategy for CRCLMs, mainly because of the extensive heterogeneity in the patients. In fact, although we consider them a population, they represent different clinical and biological subtypes requiring different approaches. Furthermore, results from different studies in this setting may be difficult to interpret, also because the definitions of different patient subgroups are unclear and overlapping. In this review we discuss the results of clinical trials evaluating the role of chemotherapy in the multimodal management of CRCLMs, in either the pre- or postoperative setting. Then we identify three main categories of CRCLM patients, providing clinical recommendations for each
Prognostic value for incidental antihypertensive therapy with β-blockers in metastatic colorectal cancer
No full textPrevious studies suggested that the incidental use of β-blockers might influence clinical outcome in solid tumors. We assessed the correlation between the incidental use of β-blockers and clinical outcome in colorectal cancer patients treated with first-line chemotherapy alone or in combination with bevacizumab in metastatic colorectal cancer patients. We collected data from 235 metastatic colorectal cancer patients treated with first-line chemotherapy alone (128 patients) or with bevacizumab (107 patients). Patients were stratified for clinical factors such as β-blockers use, age, sex, and site of metastases, previous adjuvant chemotherapy and ECOG performance status. In the chemotherapy alone group patients receiving β-blockers showed an improved overall survival (median OS 41.3 vs 25.7 months, P = 0.03, HR: 2.26, 95% CI: 1.05-3.24). A significant relationship with improved response rate was also evident for B-blocker users (P = 0.044). On the contrary in the β-blockers users group treated with chemotherapy in combination with bevacizumab we observed a trend toward a worse overall survival although nonstatistically significant (median OS 18.5 vs 23.6 months, HR: 0. 89, 95% CI: 0.38-2.03, P = 0.77). Our analysis confirmed a potential prognostic role for the use of β-blockers in colorectal cancer patients treated with chemotherapy. Our findings also suggest a potential worse outcome for patients on β-blockers receiving bevacizumab. Future prospective studies should include the incidental use of β-blockers as stratification factor for clinical outcome
Panitumumab for the treatment of metastatic colorectal cancer: A review
No full textIn recent years, the treatment of metastatic colorectal cancer (mCRC) has evolved significantly with the increase of new therapeutic options, leading to an improved median survival for these patients. In particular, the identification of molecular targets in tumor cells has led to the introduction of biological drugs for the treatment of mCRC. Panitumumab is a fully human monoclonal antibody that binds the EGF receptor of tumor cells and inhibits downstream cell signaling with antitumor effect on inhibition of tumor growth. Its use has been approved by randomized clinical trials as monotherapy in chemorefractory patients or combined with chemotherapy in the treatment of RAS wild-type mCRC, where it demonstrated a significant improvement in survival and response rate. The purpose of this review is to analyze the use and efficacy profile of panitumumab, particularly focusing on recently reported data on its use, and future perspectives in patients with mCRC
Toward molecularly selected chemotherapy for advanced gastric cancer: state of the art and future perspectives.
No full textIn the last few years therapeutic options for gastric cancer patients have slowly, but constantly expanded following the introduction of both new chemotherapy agents and innovative indications for treatment. Along with the medical therapy also our knowledge of the molecular mechanisms underlying this disease has progressively improved. However although the available treatment options have undoubtedly increased no clear definitive indications can be made for a standard chemotherapy regimen and we are still unable to accurately select the appropriate treatment for the appropriate patient. Many molecular determinants of response/toxicity to chemotherapy agents have been identified, but only few of them seem to possess the necessary potential for a subsequent application in the clinical practice. Some of these factors have also been indicated as a therapeutic target for a novel class of anti-cancer compounds. This systematic review will analyse available data about these factors with the aim to constitute a starting point for future research
Molecular biomarkers of resistance to anti-EGFR treatment in metastatic colorectal cancer, from classical to innovation.
No full textBACKGROUND:
Systematic dissection of the EGFR pathway was considered as the best way to identify putative markers of resistance to anti-EGFR therapies. This kind of approach leaves other, less known but by no means less important, putative mechanisms of resistance. We tried to shed some light on these mechanisms of resistance.
MATERIALS AND METHODS:
We performed a research through Pubmed database of all published articles highlighting mechanisms of resistance to Cetuximab and Panitumumab based therapies, published in 2000-2012 period.
CONCLUSIONS:
We reviewed the "classical" molecular factors, extensively analyzed as predictive factors for efficacy to anti-EGFR therapy, such as K-ras, B-raf, and PI3K-mTOR-Akt, focusing on their predictive or prognostic value and on the controversial aspects of the biomarker analysis for clinical practice. On the second part we will then move on to other less known molecular markers, for the future understanding of biological mechanisms underlying anti-EGFR therapy resistance, such as non-canonical heterodimer candidates, microRNA, IGF1-IGF1R, HGF-cMET and secondary mutations of EGFR
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