Development of a Nephrotic Syndrome in a Patient with Gastrointestinal Stromal Tumor during a Long-Time Treatment with Sunitinib

A patient with advanced gastrointestinal stromal tumor (GIST) receiving second-line treatment with sunitinib developed edema, increase of the serum creatinine, weight gain, nephrotic syndrome with proteinuria of 12 g/24 h, dyslipidemia, hypoalbuminemia and also presented with hypertension. A kidney biopsy showed an immunocomplex glomerulonephritis. Steroid treatment was started, but the clinical conditions and laboratory values did not improve. So in the hypothesis that the nephrotic syndrome was induced by sunitinib, sunitinib was temporarily discontinued with a subsequent reduction of proteinuria and improvement in blood pressure control. In the last years, the introduction of sunitinib has modified the natural history of advanced GIST. However, due to chronic and prolonged intake of this drug, there is increasingly frequent detection of late and unknown toxicities in clinical practice. In particular, the late renal toxicity from sunitinib may be the primary clinical problem with this drug in the case of prolonged treatment. Monitoring of kidney function and blood pressure should be performed for early detection of side effects such as hypertension and kidney dysfunction in advanced GIST patients receiving long-term treatment with sunitinib. A clinical collaboration between oncologists and nephrologists could be useful with the objective to optimize the management of sunitinib.Key words: Gastrointestinal stromal tumor, Sunitinib, Nephrotic syndrome, Vascular endothelial growth factor, Proteinuria, Renal toxicity     

Chronic therapy in gastrointestinal stromal tumours (GISTs): the big gap between theory and practice

The advent of imatinib mesilate, an oral target therapy, has dramatically changed the natural history of gastrointestinal stromal tumours (GISTs). This rare neoplasm has become the paradigm of targeted therapies in solid tumours, also introducing a home-based cure concept in oncology. However, it should be retained that oral drug administration entails new and relevant management problems. Multiple studies have demonstrated the efficacy of imatinib in GISTs associated with a good toxicity profile. However, the efficacy of imatinib, according to its mechanism of action and pharmacokinetics, is closely related to daily assumption. No interruption or ??jerky?? assumption is permitted in order to avoid efficacy loss. Thus, the issue of treatment adherence is crucial for a successful strategy and should not be overlooked. We think that dealing with the problem means assessing a wide spectrum of not only clinical and general but also psychological and individual aspects. Furthermore, both patient and family should play an active role in the ??cure process?? and physicians should reduce the distance separating them from their patients due to home-based target therapy, promoting communication and consolidation of a trust-based physician?Cpatient relationship. Several advantages have been introduced by oral target therapies in oncology. However, chronic drug administration, even if generally well tolerated, when prolonged for an undetermined time could heavily impact on patients?? quality of life. This could induce non-prescribed drug suspension, with negative impact on disease control. More studies would be necessary in order to detect real patients?? adherence, to correlate drug assumption with clinical outcome and to optimize imatinib treatment strategy.     

Evidence for efficacy of the Italian national pre-participation screening programme for identification of hypertrophic cardiomyopathy in competitive athletes.

AIMS: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden death in young athletes, and substantial interest persists in strategies for timely identification. We assessed the diagnostic efficacy of Italian pre-participation screening programme with 12-lead ECG (in addition to history and physical examination) for identification of HCM. METHODS AND RESULTS: Four thousand four hundred and fifty members of the Italian national teams, initially judged eligible for competition as a result of systematic pre-participation screening across Italy, subsequently underwent clinical and echocardiographic examination at the Institute of Sports Medicine and Science (Rome) to assess the presence of previously undetected HCM. None of the 4450 athletes showed clinical evidence of HCM. Other cardiac abnormalities were detected in only 12 athletes, including myocarditis (n=4), mitral valve prolapse (n=3), Marfan's syndrome (n=2), aortic regurgitation with bicuspid valve (n=2), and arrhythmogenic right ventricular cardiomyopathy (n=1). In addition, echocardiography identified four athletes with borderline left ventricular wall thickness (i.e. 13 mm) in the 'grey zone' of overlap between HCM and athlete's heart. In two of these athletes, subsequent genetic analysis or clinical changes over an average 8-year follow-up resulted, respectively, in a definitive or possible diagnosis of HCM. CONCLUSION: The Italian national pre-participation screening programme including 12-lead ECG appears to be efficient in identifying young athletes with HCM, leading to their timely disqualification from competitive sports. These data also suggest that routine echocardiography is not an obligatory component of broad-based screening programmes designed to identify young athletes with HCM.     

Prognostic clinical factors in pretreated colorectal cancer patients receiving regorafenib: Implications for clinical management

Background

We assessed the impact on survival of angiogenesis and inflammation-related factors, particularly LDH serum levels, platelet, neutrophil and lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR), in metastatic colorectal cancer patients receiving regorafenib monotherapy.

Methods

LDH serum levels, neutrophil, lymphocyte and platelet counts were collected at the start of regorafenib monotherapy. Cut-off values were calculated by ROC curve analysis. Survival analyses were performed by Kaplan-Meier method, and multivariate analysis by Cox method.

Results

A total of 208 patients were eligible for analysis. Among factors who were related with worse overall survival and who maintained their role at the multivariate analysis, high platelet count (Exp(b):1.4963, 95% CI:1.0130–2.2103, p = 0.0439) and high neutrophil/lymphocyte ratio (Exp(b):1.6963, 95% CI:1.0757–2.6751, p = 0.0237) were those who more deeply were related to worse overall survival. High lymphocyte count (Exp(b):0.4527, 95% CI:0.2801–0.7316, p = 0.0013) was correlated with improved overall survival.

Conclusions

High neutrophil, high platelet, low lymphocyte count and/or high NLR may represent negative prognostic factors in patients receiving regorafenib monotherapy. It is advisable that these factors are taken into account in the design of subsequent trials in colorectal cancer patients receiving this drug.     

Pancreatic cancer: progress in cancer therapy

Pancreatic cancer continues to be a highly lethal disease. In fact the overall 5-year survival rate is less than 4% and has hardly improved over the past two decades. Surgery is the only potential curative treatment, but the majority of patients have an unresectable disease at the diagnosis. After the demonstration in 1997 that gemcitabine could lead to an improvement in clinical benefit and overall survival this chemotherapy agent became the standard of care for advanced pancreatic cancer patients. Several authors tried to improve results obtained with single agent gemcitabine by exploring the activity of novel chemotherapy on biologically targeted agents in combination with gemcitabine. Unfortunately, global findings were often disappointing with only a marginally significant survival benefit. New treatment strategies and a more careful evaluation of innovative therapies are clearly needed for this disease. In this review we will focus on treatment strategies both in resectable and advanced pancreatic cancer.     

Pharmacological evidence for beta3 adrenoceptors in the control of rat gastric acid secretion

The effect of the ₃-adrenoceptor agonist BRL37344 on gastric acid secretion evoked by different secretory stimuli was investigated in anaesthetized rats with lumen-perfused stomachs in comparison with the ₂-adrenoceptor agonist clenbuterol. Intravenous injections of BRL37344 (1–10 mol/kg) and clenbuterol (0.01–1 mol/kg) dose-dependently reduced 2-deoxy-D-glucose-induced acid secretion, with BRL37344 about forty times less potent than clenbuterol. BRL37344 (0.1–3 mol/kg) inhibited pentagastrin-induced acid output, whereas clenbuterol was effective only at high doses (10–100 mol/kg). The inhibitory effect of BRL37344 on pentagastrin-induced acid secretion was not modified by the nonselective –adrenoceptor antagonist propranolol, but it was prevented by bupranolol, a ₃-adrenoceptor antagonist. Furthermore, neither BRL37344 (10 mol/kg) nor clenbuterol (100 mol/kg) modified the acid secretion induced by histamine. These data suggest that ₃ adrenoceptors have an inhibitory role in the control of rat gastric acid secretion induced by indirect stimuli.