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.

scholarly journals Children’s Oxygen Administration Strategies And Nutrition Trial (COAST-Nutrition): a protocol for a phase II randomised controlled trial

2021 ◽  
Vol 6 ◽  
pp. 221
Author(s):  
Sarah Kiguli ◽  
Peter Olopot-Olupot ◽  
Florence Alaroker ◽  
Charles Engoru ◽  
Robert O. Opoka ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Phase Ii ◽  
Nutritional Support ◽  
Cell Function ◽  
Action Plan ◽  
Controlled Trial ◽  
Severe Pneumonia ◽  
Phase Iii ◽  
Randomised Controlled ◽  
Usual Diet

Background: To prevent poor long-term outcomes (deaths and readmissions) the integrated global action plan for pneumonia and diarrhoea recommends under the ‘Treat’ element of Protect, Prevent and Treat interventions the importance of continued feeding but gives no specific recommendations for nutritional support. Early nutritional support has been practiced in a wide variety of critically ill patients to provide vital cell substrates, antioxidants, vitamins, and minerals essential for normal cell function and decreasing hypermetabolism. We hypothesise that the excess post-discharge mortality associated with pneumonia may relate to the catabolic response and muscle wasting induced by severe infection and inadequacy of the diet to aid recovery. We suggest that providing additional energy-rich, protein, fat and micronutrient ready-to-use therapeutic feeds (RUTF) to help meet additional nutritional requirements may improve outcome. Methods: COAST-Nutrition is an open, multicentre, Phase II randomised controlled trial in children aged 6 months to 12 years hospitalised with suspected severe pneumonia (and hypoxaemia, SpO2 <92%) to establish whether supplementary feeds with RUTF given in addition to usual diet for 56-days (experimental) improves outcomes at 90-days compared to usual diet alone (control). Primary endpoint is change in mid-upper arm circumference (MUAC) at 90 days and/or as a composite with 90-day mortality. Secondary outcomes include anthropometric status, mortality, readmission at days 28 and 180. The trial will be conducted in four sites in two countries (Uganda and Kenya) enrolling 840 children followed up to 180 days. Ancillary studies include cost-economic analysis, molecular characterisation of bacterial and viral pathogens, evaluation of putative biomarkers of pneumonia, assessment of muscle and fat mass and host genetic studies.   Discussion: This study is the first step in providing an option for nutritional support following severe pneumonia and will help in the design of a large Phase III trial. Registration: ISRCTN10829073 (6th June 2018) PACTR202106635355751 (2nd June 2021)

Updated use of first-line chemotherapy for advanced pancreatic cancer: FOLFIRINOX versus gemcitabine.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6607-6607
Author(s):  
Thomas H. Cartwright ◽  
Aimee Ginsburg Arlen ◽  
Lalan S. Wilfong ◽  
Robyn K. Harrell ◽  
J. Russell Hoverman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Advanced Pancreatic Cancer ◽  
Community Setting ◽  
Standard Of Care ◽  
The United States ◽  
Age At Diagnosis ◽  
Phase Iii ◽  
Combination Regimen ◽  
First Line ◽  
Asco 2012

6607 Background: Pancreatic cancer (PC) is the fourth leading cause of death in the United States. It is estimated that 45,220 patients will be diagnosed in 2013 and 38,460 will die (Siegel, CA Cancer J Clin 2013). Gemcitabine has long been the standard of care chemotherapy. Recent advances in treatment created a combination regimen (oxaliplatin, irinotecan, leucovorin, fluorouracil [FOLFIRINOX]) for patients with good Karnofsky performance status (PS) (Conroy, NEJM 2011). This retrospective analysis was conducted as an update to results reported at ASCO 2012 (Ginsburg Arlen, JCO 2012) to evaluate characteristics and overall survival (OS) of patients receiving FOLFIRINOX and gemcitabine-based treatments in a large outpatient community setting. This is the largest study describing FOLFIRINOX patients to date. Methods: Patients with advanced PC treated within The US Oncology Network entered into the iKnowMed (iKM) database between June 2010 and November 2012 were included. Patterns of treatment were characterized by the median age at diagnosis, sex, PS, and first-line metastatic chemotherapy prescribed. The primary endpoints of the analysis were OS and uptake of FOLFIRINOX within the network. Results: Compared to ASCO 2012 results, 1,000 additional patients were identified in iKM. Of the 1,714 total patients, 24% received FOLFIRINOX (up from 13% in 2012) and 76% gemcitabine-based therapy (87% in 2012). Increased utilization of FOLFIRINOX for patients with good PS began in June 2010. For all patients (55% male), the median age at diagnosis was 67 years and the majority (85%) had a PS of 70% or greater. The OS was significantly longer for FOLFIRINOX (9.6 mos) versus gemcitabine (6.3 mos) (p<0.0001). This held true for PS of 70% or greater patient given FOLFIRINOX (9.6 mos) versus gemcitabine (7 mos) (p<0.0001). Conclusions: Utilization of FOLFIRINOX has continued to expand after the publication of phase III trials. Our data in a community setting supports a survival advantage for FOLFIRINOX. Although the magnitude of benefit may be smaller in the community, we agree that FOLFIRINOX should become a standard of care for good PS patients.

The impact of 2nd-line treatment (tx) after 1st-line Gemcitabine plus Nab-paclitaxel (GemNab) in advanced pancreatic cancer (APC) patients (pts).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16759-e16759
Author(s):  
Brunella Di Stefano ◽  
Maria Bensi ◽  
Cinzia Bagalà ◽  
Alexia Spring ◽  
Marta Chiaravalli ◽  
...  
Keyword(s):  
Baseline Level ◽  
Advanced Pancreatic Cancer ◽  
Uncinate Process ◽  
Phase Iii ◽  
Combination Regimen ◽  
Homogeneous Population ◽  
Significant Survival ◽  
Ca 19.9 ◽  
Ecog Ps ◽  
The Impact

e16759 Background: Three main phase III randomized studies investigated the role of 2nd-line tx in APC pts. The PANCREOX study failed to demonstrate a survival advantage of mFOLFOX vs 5FU/LV. Conversely, the CONKO-003 and NAPOLI-1 trials, demonstrated a significant survival improvement from the combination regimen OFF and 5FU+Nal-IRI, respectively, in comparison to 5FU/LV alone. Recently, final OS analysis from NAPOLI-1 demonstrated an association of specific characteristics (ECOG PS, age, Ca 19.9 baseline level, neutrophil-to-lymphocyte ratio and no liver metastases (m)) with OS > 1 year. The main limit of all these studies was due to the period they were carried out: no pts received 1st-line GemNab. Hence, we retrospectively analysed an homogeneous population of APC treated with 1st-line GemNab at our Institution, investigating the impact of 2nd-line tx. Methods: APC pts receiving a 2nd-line tx after 1st-line GemNab were included in the analysis. The following variables were collected: gender; age ( > vs ≤ 55 years and ≥ vs < 70 years ); baseline ECOG PS (0-1 vs 2-3); Ca 19.9 baseline level (≥ vs < 200); anamnesis of diabetes; site of primary tumor (head/uncinate process vs body/tail); number of m sites (1 vs > 1); m sites (liver, peritoneum, lung, nodes); RECIST response and ETS during 1-line GemNab. Univariate and multivariate analyses for PFS and OS were performed. Results: Out of 167 APC pts progressed to 1st-line GemNab, 93 (56%) pts received a 2nd-line tx, specifically 58 pts received an oxa-based regimen, 11 FOLFIRINOX, 8 FOLFIRI and 16 pts received other tx. Median 2nd-line PFS and OS were 3.3 and 5.6 months, respectively. Out of 87 pts evaluable for response, 7 pts achieved a partial response and 27 a stable disease, with a RR and a disease control rate (DCR) of 8% and 39%, respectively. Pts with baseline ECOG PS 0-1 had a significant better outcome in comparison to pts with PS 3-4 (PFS 4.2 vs 1.2 months, p < 0.0001; OS 7.2 vs 2.6 months, p = 0.0001). This significant association with survival parameters and ECOG PS was confirmed at the multivariate analysis. Conclusions: Despite the limited number of pts evaluated and the restrospective nature of our analysis, our results are in line with previous evidences, confirming the importance of a 2nd-line combination tx, when feasible, as well in an homogeneous population of APC pts treated with 1st-line GemNab. On the basis of our results, ECOG PS may be considered a prognostic factor and the choice of 2nd-line tx should be guided in primis by the baseline general conditions of APC pts.

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 Metastatic Pancreatic Cancer: Are We Making Progress in Treatment?

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Joanne Chiu ◽  
Thomas Yau
Keyword(s):  
Pancreatic Cancer ◽  
Targeted Therapy ◽  
Survival Benefit ◽  
Performance Status ◽  
Symptom Relief ◽  
Advanced Pancreatic Cancer ◽  
Cytotoxic Agents ◽  
Combination Regimen ◽  
Significant Survival ◽  
Clinical Conditions

Development of systemic treatment for advanced pancreatic cancer (APC) has been challenging. After fluorouracil, gemcitabine (GEM) became the treatment of choice based on its benefit of symptom relief. Many cytotoxic agents have been combined with GEM in search of regimens with improved survival benefit. However, there were only marginal benefits in people with good performance status. Recently, the combination regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) was found to achieve unprecedented survival benefit and has become the preferred option for patients with good clinical conditions. On the other hand, many biological agents have been combined with GEM, but only erlotinib was found to derive statistically significant survival advantage. However, the effect was too small to be appreciated clinically. The effort in development of targeted therapy in APC continues. This paper summarized key findings in the development of chemotherapy and targeted therapy for APC patients and discussed future directions in management.

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.

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