Safety and Efficacy of a First-Line Chemotherapy Tailored by G8 Score in Elderly Metastatic or Locally Advanced Gastric and Gastro-Esophageal Cancer Patients: A Real-World Analysis.

Introduction: Gastric (GC) and gastro-esophageal cancer (GEC) are common neoplasms in the elderly. However, in clinical practice, the correct strategy for elderly patients who might benefit from chemotherapy (CT) is unknown. Prospective data are still poor. In this context, we performed a retrospective analysis of GC patients aged ≥75 years and treated at our institutions. Material and Methods: We retrospectively analyzed 90 patients with confirmed metastatic GC or GEC, treated with an upfront CT. Inclusion criteria were patients aged ≥75 years, PS 0−2, normal bone marrow/liver/renal function and no major comorbidities. All patients received a G8 score, and some patients with G8 ≤14 received a comprehensive geriatric assessment (CGA). The primary goal was to perform a safety evaluation based on the incidence of adverse events (AE), and the secondary goal was to determine the efficacy (PFS and OS). The chi-square test and the Kaplan−Meier method were used to estimate the outcomes. The statistical significance level was set at p < 0.05. Results: Toxicity rates were quite low: G1/G2 (51.1%) and G3/G4 (25.5%). No toxic deaths were reported. The median PFS was 6.21 months and the median OS 11 months. The G8 score and PS ECOG significantly influenced both PFS and OS. A statistically significant correlation among G8, weight loss, hypoalbuminemia and risk of G3/G4 adverse events was also found. Conclusion: Our research on selected elderly patients did not detect broad differences of efficacy and tolerability compared to a young population. Our study, although retrospective and small-sized, showed that G8 score might be an accurate tool to identify elderly GC/GEC patients who could be safely treated with CT, further recognizing patients who could receive a doublet CT and who may require a single agent chemotherapy or a baseline dose reduction.

Onco-geriatric approach for the management of older patients with cancer.

INTRODUCTION AND RATIONALE: The number of older cancer patients is increasing with global aging of the population. A close interaction between oncologists and geriatricians becomes necessary to (1) better evaluate the elders' health status, (2) determine their residual clinical/biological reserves, and (3) optimize the provided medical care. In fact, aggressive antineoplastic managements are often denied to older patients, possibly because of the common misconception suggesting older age and/or clinical complexity as absolute contraindications to advanced treatments. METHODS: The primary aim of the presented project is to assess whether assigning a geriatrician to provide daily medical care to older cancer patients (aged 65 years and older) admitted to an oncology ward increases the number of patients eligible for a chemotherapeutic and/or surgical intervention. The project is articulated in 2 phases: (1) a retrospective phase based on analysis of data collected over the 2 years before the beginning of the study, and (2) a prospective 2-year intervention. Additional information about clinical conditions, biological parameters, adverse drug reactions, body composition, physical function, and 1-year health-related events will also be recorded. OUTCOMES: The combination of expertise from oncologists and geriatricians is likely to result in (1) an improved selection of candidates for interventions aimed at increasing disability-free life expectancy and/or overall survival, and (2) a more rational exclusion of patients at higher risk of toxicity or with poor prognosis. In this article, the development of an onco-geriatric unit aimed at the evaluation, management, and treatment of older women with gynecological cancer is also described.

Responsiveness to cholinesterase inhibitors in Alzheimer's disease: a possible role for the 192 Q/R polymorphism of the PON-1 gene.

Cholinesterase inhibitors (ChEIs) are the most established treatment strategy in Alzheimer's disease (AD). However, the responsiveness to these drugs is widely heterogeneous and the majority of AD subjects do not respond to treatment. Paraoxonase-1 (PON-1) is a potent endogenous ChEI and has been widely studied for its ability to hydrolyze environmental neurotoxins. Serum levels and biological activity of PON-1 display wide inter-individual variability and are strongly influenced by a common polymorphism at position 192 of the PON-1 gene. Here, we evaluated whether this gene variation is associated with differences in the ability of AD subjects to respond to therapy with ChEIs. We found that individuals that respond to ChEIs had a significantly higher frequency of the R allele, compared to non-responders (P<0.05). This study indicates that the 192 Q/R polymorphism of the PON-1 gene might influence responsiveness to ChEIs, with potentially important implications for the treatment of AD. Mutations of genes encoding for endogenous modulators of the cholinergic system should merit further investigation as prognostic indicators of individual response to treatment in AD subjects.