DDP4 inhibitors as novel agents in improving survival in diabetic patients with CRC and lung cancer: A SEER-Medicare study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14633-e14633
Author(s):  
Rohit Bishnoi ◽  
Young-Rock Hong ◽  
Chintan Shah ◽  
azka ali ◽  
William Paul Skelton ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Survival Advantage ◽  
Diabetic Patients ◽  
Dpp4 Inhibitors ◽  
Dpp4 Inhibitor ◽  
Significant Survival Advantage ◽  
Significant Survival ◽  
Inhibitor Treatment ◽  
Dpp4 Inhibition

e14633 Background: DPP4 is a cell surface protein that is widely expressed on different tissues and can play important role in tumor biology by acting as a tumor suppressor or activator, depending upon the level of expression and interaction with the microenvironment and chemokines. DPP4 inhibitors are a class of drug used in the clinical setting to treat diabetes mellitus type II (DM-II) while recent research has suggested that they play a role in regulating tumor growth. Methods: We conducted this large population database Surveillance Epidemiology and Endpoint Research (SEER-Medicare) study to evaluate the role of DPP4 inhibitors on the overall survival (OS) of patients with colorectal and lung cancers. Results: Our results showed that diabetic patients with colorectal cancer (CRC) or lung cancer who were treated with DPP4 inhibitors exhibited a statistically significant survival advantage (HR of 0.89; 95% CI: 0.82-0.97, p = 0.007) that remained significant after controlling for all other confounders. When DPP4 inhibitors were used in combination of metformin, which is already known to improve OS in many cancers, the survival advantage was even more pronounced (HR of 0.83; 95% CI: 0.77-0.90, p < 0.0001). When results were analyzed for CRC-only cohort, the use of DPP4 inhibitors alone had a very positive survival advantage trend (HR of 0.87; 95% CI: 0.75-1.00, p = 0.055) whereas the combined use of DPP4 inhibitors and metformin was associated with statistically significant survival advantage (HR of 0.77; 95% CI: 0.67-0.89, p = 0.003). Similarly, in the lung cancer cohort, the DPP4 inhibitor group exhibited a potential survival advantage (HR of 0.93; 95% CI: 0.83-1.03, p = 0.153), while lung cancer patients treated with the combination of DPP4 inhibitors and metformin showed statistically significant survival advantage (HR of 0.88; 95% CI: 0.80-0.97, p = 0.010). Conclusions: These results again establish that DPP4 inhibition in CRC and lung cancer is associated with the suppression of tumor growth and improved OS. The beneficial effects of DPP4 inhibitor treatment are additionally improved when DPP4 inhibitors are used in combination with metformin. While the exact mechanism involved in the observed benefit of DPP4 inhibitor treatment in cancer remains to be elucidated, one possibility may be due to the effect of DPP4 inhibition on immunoregulation of cancer.

scholarly journals The significant survival advantage of female sex in nasopharyngeal carcinoma: a propensity-matched analysis

2015 ◽  
Vol 112 (9) ◽  
pp. 1554-1561 ◽  
Author(s):  
P-Y OuYang ◽  
L-N Zhang ◽  
X-W Lan ◽  
C Xie ◽  
W-W Zhang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Survival Advantage ◽  
Female Sex ◽  
Significant Survival Advantage ◽  
Significant Survival

scholarly journals Longer Leukocytes Telomere Length Predicts a Significant Survival Advantage in the Elderly TRELONG Cohort, with Short Physical Performance Battery Score and Years of Education as Main Determinants for Telomere Elongation

2021 ◽  
Vol 10 (16) ◽  
pp. 3700
Author(s):  
Sofia Pavanello ◽  
Manuela Campisi ◽  
Alberto Grassi ◽  
Giuseppe Mastrangelo ◽  
Elisabetta Durante ◽  
...  
Keyword(s):  
Telomere Length ◽  
Physical Performance ◽  
Mortality Risk ◽  
The Elderly ◽  
Male Gender ◽  
Short Physical Performance Battery ◽  
Survival Advantage ◽  
Significant Survival Advantage ◽  
Significant Survival ◽  
Main Determinants

Leukocyte telomere length (LTL) represents a key integrating component of the cumulative effects of environmental, lifestyle, and genetic factors. A question, however, remains on whether LTL can be considered predictive for a longer and healthier life. Within the elderly prospective TRELONG cohort (n = 612), we aimed to investigate LTL as a predictor of longevity and identify the main determinants of LTL among many different factors (physiological and lifestyle characteristics, physical performance and frailty measures, chronic diseases, biochemical measurements and apolipoprotein E genotyping). We found an ever-increasing relationship between LTL quartiles and survival. Hazard ratio analysis showed that for each unit increase in LTL and Short Physical Performance Battery (SPPB) scores, the mortality risk was reduced by 22.41% and 8.78%, respectively. Conversely, male gender, Charlson Comorbidity Index, and age threatened survival, with mortality risk growing by 74.99%, 16.57% and 8.5%, respectively. Determinants of LTL elongation were SPPB scores (OR = 1.1542; p = 0.0066) and years of education (OR = 1.0958; p = 0.0065), while male gender (OR = 0.4388; p =  0.0143) and increased Disease Count Index (OR = 0.6912; p  =  0.0066) were determinants of LTL attrition. Longer LTL predicts a significant survival advantage in elderly people. By identifying determinants of LTL elongation, we provided additional knowledge that could offer a potential translation into prevention strategies.

scholarly journals Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group [see comments]

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4064-4077 ◽  
Author(s):  
R Hehlmann ◽  
H Heimpel ◽  
J Hasford ◽  
HJ Kolb ◽  
H Pralle ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Interferon Alpha ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Survival Advantage ◽  
Myelogenous Leukemia ◽  
Prognostic Scores ◽  
Significant Survival Advantage ◽  
Significant Survival ◽  
Central Interest

As curative bone marrow transplantation is available only to a minority of patients with chronic myelogenous leukemia (CML), drug therapy remains of central interest. Several nonrandomized studies have suggested that interferon-alpha (IFN) may prolong survival in CML. In a randomized multicenter study the influence of IFN versus busulfan or hydroxyurea (HU) on survival of Philadelphia-positive (Ph+) CML was examined. A total of 513 Ph+ patients were randomized for treatment as follows: 133 for IFN, 186 for busulfan, and 194 for HU. IFN-treated CML patients have a significant survival advantage over busulfan-treated (P = .008), but not over HU-treated patients (P = .44). The longer survival is due to slower progression to blast crisis. Median survival of IFN-treated patients is 5.5 years [5-year survival, 59%; 95% confidence interval (CI), 48%-70%], of busulfan-treated patients, 3.8 years (5-year survival, 32%; CI, 24%-40%), and of HU-treated patients, 4.7 years (5-year survival, 44%; CI, 36%-53%). Patients who continue on IFN survive longer than those in whom IFN is discontinued before blast crisis (P = .007). Complete hematologic IFN-responders have a survival advantage over partial responders or nonresponders (P = .02). Cytogenetic IFN-responders have no significant survival advantage over nonresponders (P = .2). Patients who attain white blood cell (WBC) counts of 10 x 10(9)/L or less have a survival advantage in the IFN (P = .007) and HU (P = .05) groups. Whereas toxicity in the IFN group was considerably higher than in the busulfan or HU groups, long-lasting cytopenias necessitating discontinuation of therapy as observed with busulfan have not been seen with IFN or HU. The problems of conventional prognostic scores (Sokal's score, Score 1) that we observed in IFN-treated patients support the idea that IFN changes the natural course of CML. We conclude that, with regard to survival of CML in the chronic phase, IFN is superior to busulfan and as effective as HU. Whether and to what extent IFN is superior to HU appears to depend, at least in part, on the degree of WBC suppression by HU-therapy and on the risk profile of the patients.

scholarly journals Efficacy of Fluoroquinolones against Leptospira interrogans in a Hamster Model

2007 ◽  
Vol 51 (7) ◽  
pp. 2615-2617 ◽  
Author(s):  
Matthew E. Griffith ◽  
James E. Moon ◽  
Erica N. Johnson ◽  
Kyra P. Clark ◽  
Joshua S. Hawley ◽  
...  
Keyword(s):  
Survival Advantage ◽  
Leptospira Interrogans ◽  
Hamster Model ◽  
Significant Survival Advantage ◽  
Significant Survival

ABSTRACT Ciprofloxacin, gatifloxacin, and levofloxacin were evaluated for their abilities to prevent mortality in hamsters infected with a lethal inoculum of Leptospira interrogans serovar Portlandvere. Each agent produced a statistically significant survival advantage compared to no treatment and demonstrated survival similar to that seen with doxycycline therapy.

Abstract 95: Glucagon Like Peptide-1 (GLP-1) Does Not Cause Vasodilation Even When Dipeptidyl Peptidase 4 (DPP4) is Inhibited

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Jessica K Devin ◽  
Mias Pretorius ◽  
Frederic T Billings ◽  
Hui Nian ◽  
Nancy J Brown
Keyword(s):  
Interactive Effect ◽  
Dipeptidyl Peptidase ◽  
Diabetic Patients ◽  
Baseline Heart Rate ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitors ◽  
Healthy Humans ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Dpp4 Inhibition

Glucagon-like peptide 1 (GLP-1) causes direct vasodilation in animal models. Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in diabetic patients by preventing the degradation of GLP-1. The direct effect of GLP-1 in the human vasculature, and how it is altered by DPP4 inhibition, has not been reported. This study tested the hypothesis that intra-arterial infusion of GLP-1 causes dose-dependent vasodilation, and that DPP4 inhibition potentiates the forearm blood flow (FBF) response to GLP-1 by decreasing its degradation. Eight healthy, non-obese (BMI<30 kg/m 2 ) subjects, age 28-54 years old (3 female) participated in this double-blind, placebo-controlled crossover study. On study days separated by at least one week subjects received DPP4 inhibitor (sitagliptin 200 mg p.o.) or placebo, followed by infusion of GLP-1 in the brachial artery at graded doses (0.45-3.60 pmol/min) for 5 minutes per dose. Sitagliptin significantly decreased plasma DPP4 activity (p<0.001 vs. placebo). Sitagliptin did not significantly affect baseline heart rate or baseline FBF. Baseline mean arterial pressure was significantly higher during sitagliptin than during placebo [87.13 ± 2.10 mmHg versus 84.75 ± 3.28 mmHg, p=0.037]. GLP-1 concentrations were significantly higher after sitagliptin (Left Figure; N=5). There was no effect of GLP-1 on FBF either in the presence or absence of sitagliptin. Moreover, there was no interactive effect of GLP-1 and sitagliptin on FBF (Right Figure). GLP-1 does not cause vasodilation in healthy humans even when its degradation is inhibited. These data have implications for the cardiovascular effects of DPP4 inhibitors and GLP-1 receptor agonists.

Masitinib in nonresectable pancreatic cancer: Results of a phase III randomized placebo-controlled trial.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 158-158 ◽  
Author(s):  
Gael Deplanque ◽  
Martin Demarchi ◽  
Mohamed Hebbar ◽  
Patrick J. Flynn ◽  
Bohuslav Melichar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mast Cell ◽  
Cell Function ◽  
Controlled Trial ◽  
Cell Activity ◽  
Survival Advantage ◽  
Phase Iii ◽  
Combination Regimen ◽  
Significant Survival Advantage ◽  
Significant Survival

158 Background: Masitinib is a selective c-Kit inhibitor that efficiently inhibits mast cell function. Increased mast cell activity in the tumor microenvironment has been linked to poor prognosis in pancreatic cancer (PC) patients. Methods: In a randomized (1:1 ratio), double-blind, international phase III trial, chemo-naïve PC patients (n=348) received either masitinib (9 mg/kg/day) in combination with gemcitabine (1000 mg/m2/wk) (M+G) or placebo plus gemcitabine (P+G). Primary endpoint was overall survival (OS). An ancillary pharmacogenomic study, based on RNA extracted from whole blood prior to treatment, was conducted in a subset of patients. Results: In the overall population median OS was not significantly improved in the M+G arm as compared with the P+G arm (median OS: 7.7 vs. 7.0 months, respectively; p=0.74, HR=0.90 [0.71; 1.14]). However, M+G treatment led to a significant survival advantage in two subpopulations. First, in patients with ‘pain’ at baseline (defined as a VAS score >20 mm on a 100 mm scale) (44% of patients with pain intensity data available) median OS was significantly increased from 5.4 months in the P+G arm to 8.1 months in the M+G arm (p=0.010; HR:0.61 [0.42; 0.88]); OS rates at 12 and 18 months were respectively, 32.2% and 18.2% in the M+G arm vs. 17.8% and 7.8% in the P+G arm. Second, in patients with a specific deleterious genomic biomarker (GBM) consisting of a limited number of genes (66% of patients with genetic data available), median OS was significantly increased in the M+G arm as compared with the P+G arm (11.0 vs. 5.0 months, respectively) (p=0.000038; HR=0.29 [0.17; 0.51]); OS rates at 12 and 18 months were respectively, 41.4% and 18.5% in the M+G arm vs. 11.1% and 4.2% in the P+G arm. In patients without pain (defined as VAS <5 mm and no need for opioid analgesics), median OS was 15.4 months in the P+G arm. In patients without the deleterious GBM, median OS in the P+G arm was 14.3 months. In these two patient populations M+G treatment was contraindicated. The general safety profile of the M+G combination regimen was acceptable. Conclusions: Masitinib in combination with gemcitabine provides a significant survival advantage over gemcitabine monotherapy in PC patients with ‘pain’ and patients with a specific GBM. Clinical trial information: NCT00789633.

Sign in / Sign up

Export Citation Format

Share Document