A Retrospective Study of the Effect of Metformin on Patients with Metastatic Prostate Cancer.

Introduction: Previous studies demonstrated that metformin could lead to an inhibition of proliferation of cancer cells through a shift from anabolic to catabolic metabolism. In this study, we seek to investigate the effect of metformin in metastatic prostate cancer. Methods: Patients followed at Northwell Health Zuckerberg Cancer Center during 2014-2018 were included if they were diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC) or metastatic castration-resistant prostate cancer (mCRPC), with ⩾6 months follow-up with and without metformin treatment. The primary outcomes, 6-month prostate-specific antigen (PSA) response, overall survival (OS), and radiographic progression free survival (rPFS), were evaluated. Results: There were 267 patients included in the final analysis; 196 patients had mHSPC (73.2%) and 71 had mCRPC (26.8%). Within the mHSPC subjects, there was a significant difference in OS between metformin vs nonmetformin groups (148.5 vs 85.6 months; P < .046) in a univariate analysis; patients who took metformin had a significantly longer OS than subjects who did not (median OS: 148.5 vs 86 months; P < .046). There was no significant difference between the 2 groups with respect to either PSA response rate at 6 months or rPFS or OS in patients with mHSPC in both univariate and multivariate analysis. Within the mCRPC subjects, there was no significant difference between metformin and nonmetformin groups with respect to OS (43.3 vs 51.5 months; P < 0.160) or PSA response at 6 months (38.5% vs 57.1%; p < 0.24); however, patients on metformin had a significantly shorter rPFS in both the univariate analysis (7.3 vs 17.4; P < .0002) and in the multivariate analysis (HR = 2.52; 95% CI: 1.24m 5.11; P < .0109). Conclusions: Among patients with mHSPC, use of metformin was not significantly associated with improved OS in the multivariate analysis.

A deep dive into CDK4/6 inhibitors: Evaluating real world toxicities and treatment paradigms in the elderly population.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors have become part of the standard of care in the treatment of hormone receptor positive, Her2Neu negative metastatic breast cancer. There is concern regarding the efficacy and potential increased cyclin-dependent kinase 4/6 inhibitors toxicity in the geriatric population in the community compared to the clinical trial population. METHODS: We evaluated patients treated with cyclin-dependent kinase 4/6 inhibitors from 2015 to 2019 and stratified according to age ≥70 and <70 years. Complete blood count from the first two cycles was recorded. Rates of hematologic toxicities, dose interruptions and reductions, progression-free survival, and overall survival were compared between both groups. We sought to assess the hematologic toxicities between the age groups and the relationship between previous chemotherapy exposure, bone metastasis and starting cyclin-dependent kinase 4/6 inhibitors dose with progression-free survival and overall survival. RESULTS: A total of 202 patients were included, 73 were ≥70 years and 129 were <70 years of age. There was no association between age group and grade of neutropenia or thrombocytopenia. There was a profound association between progression-free survival and overall survival and starting dose, where patients with recommended starting dose had higher progression-free survival and overall survival than those with a reduced dose (p = 0.0003 and p = 0.04). CONCLUSIONS: Our study showed similar progression-free survival and overall survival between age groups without significant differences in neutropenia or thrombocytopenia toxicity. Nevertheless, we found an association between starting dose and progression-free survival and overall survival that has not been previously reported. Given the good tolerability across age groups and the improvement in progression-free survival and overall survival, patients should be treated at the cyclin-dependent kinase 4/6 inhibitors recommended dose and monitored appropriately.

A contemporary review of rearranged during transfection-selective inhibitors.

OBJECTIVE: Rearranged during transfection genes are present in 1-2% of patients who have non-small cell lung cancer and 10-30% of patients with papillary thyroid cancer. The objective of this article is to review the current rearranged during transfection inhibitors indicated for patients with rearranged during transfection-mutated cancers and their future directions.Data sources: The pivotal phase I/II studies for selpercatinib and pralsetinib were evaluated. Current studies on rearranged during transfection inhibitors were searched on ClinicalTrials.gov using the key word "RET."Data summary: Selpercatinib and pralsetinib were the first two U.S. Food and Drug Administration-approved rearranged during transfection-selective inhibitors for advanced or metastatic rearranged during transfection fusion-positive non-small cell lung cancer, rearranged during transfection-mutant medullary thyroid cancer, and rearranged during transfection fusion-positive thyroid cancer. Both agents showed promising efficacy with objective response rate ranging from 60% to 73% in all aforementioned rearranged during transfection-mutated cancers. Additionally, benefits were seen even in patients with intracranial metastasis at baseline. Both showed favorable safety profiles. Some common class adverse events included elevated liver function tests and hypertension. Hematologic side effects such as anemia and neutropenia were more common with pralsetinib. Selpercatinib had interactions with acid suppressive therapy and specific instructions when used concomitantly. CONCLUSIONS: While the rearranged during transfection inhibitors are generally well-tolerated, each agent possesses slightly different efficacy, side-effect profile, and drug-drug interactions.

Single nucleotide polymorphisms in sweet, fat, umami, salt, bitter and sour taste receptor genes are associated with gustatory function and taste preferences in young adults.

Taste is a fundamental mechanism whereby compounds are detected orally, yet it is highly variable among individuals. The variability in taste that is attributable to genetics is not well-characterized despite its potential role in food selection, and therefore, eating habits that contribute to risk of overweight and obesity. In order to implicate measures of taste function and preference as potentially deterministic factors in adverse eating behaviors that lead to obesity, it must be shown that a relationship exists between genetic variation in taste receptor genes and psychophysical measures of taste in the absence high body mass index. The primary objective of this pilot study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in taste receptor genes and 3 different psychophysical measures of taste in healthy young adults. Sweet, salt, umami, fat, sour, and bitter taste receptor gene SNPs were genotyped in 49 participants (ages 24.6 ± 0.6 years) who completed testing to determine oral detection threshold (DT), suprathreshold sensitivity (ST) and taste preference (PR). A simultaneous association test was conducted between each SNP and the 3 taste outcomes (DT, ST, and PR). Twelve SNPs were associated with at least one of the 3 taste outcomes. Associations were observed between SNPs in taste receptor genes and psychophysical measures of sweet, fat, umami, and salt taste. These results suggest that differences in interindividual psychophysical measures of tastes, namely DT, ST, and PR, may be partially attributed to genetic variation in taste receptor genes. Future studies are warranted to investigate if these findings have consequences for habitual dietary intake of foods that elicit these tastes.

Taste Sensitivity and Taste Preference Measures Are Correlated in Healthy Young Adults.

Taste is fundamentally important for food selection. Although measures of taste sensitivity and preference have been refined over several decades, it remains largely unknown how these measures relate to each other and to food preferences. The objectives of this study were to examine, in healthy adults (age 24.6 ± 0.6 years, n = 49), 1) correlations among measures of taste sensitivity, including detection threshold (DT) and suprathreshold sensitivity (ST), and taste preference (PR) within sweet, salt, sour, umami, and [...] fat tastes; and 2) underlying associations [...] among DT, ST, and PR measurements using principal component analysis. DTs and STs were negatively correlated within each taste modality. Salt, sweet, and umami DTs and STs were positively and negatively correlated with PRs, respectively. No correlations were observed between sour and fat DTs, STs, and PRs. Two principal components accounted for 41.9% of the variance and produced 3 clear clusters consisting of DTs, STs, or PRs from each taste modality. Sweet PR and fat ST deviated from the clusters and may, therefore, be driven by different factors. No associations were observed between measured PR and ST with self-reported food PRs. Overall, this study provides evidence that higher sensitivities only to salt, sweet, or umami taste are associated with a decrease in the PR for these tastes. These findings demonstrate the importance of investigating taste sensitivity together with PR to gain a more complete understanding of the determinants of food selection.

A rare Krukenberg tumor arising from a primary adenocarcinoma of the small intestine.

OBJECTIVE: A Krukenberg tumor is a malignancy in the ovary that metastasizes from a primary site. Here, we report a very rare case of bilateral Krukenberg tumors of the ovaries arising from a primary adenocarcinoma of the small intestine in a 53-year-old Taiwanese woman. CASE REPORT: The patient presented with a 3-month history of abdominal distension and acid regurgitation. Gastroscopy and colonoscopy findings were negative. According to the preoperative image, we highly suspected that the small bowel mass was the primary tumor with metastatic tumors to bilateral ovarian masses. The diagnosis was made immediately after operation. Results from pathology and immunohistochemical report confirmed our diagnosis. CONCLUSION: The primary lesion of a Krukenberg tumor is generally too small to be detected. Thus, careful radiographic and endoscopic exploration of the digestive system is necessary to detect the primary tumor. Immunohistochemical evaluation is also useful for determining the primary site of the adenocarcinoma.