Calcium channel blockers use and overall survival in pancreatic cancer patients receiving gemcitabine.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15756-e15756 ◽  
Author(s):  
Leszek Kraj ◽  
Andrzej Śliwczyński ◽  
Joanna Krawczyk-Lipiec ◽  
Krzysztof Woźniak ◽  
Anna Waszczuk-Gajda ◽  
...  

e15756 Background: Preclinical studies have shown that calcium channel blockers (CCB) may potentiate anticancer effect of chemotherapy via intra-cellular drug accumulation. Gemcitabine-based chemotherapy is commonly used in pancreatic cancer (PC) patients. The aim of this study was to determine whether CCB may affect overall survival (OS) in PC patients receiving gemcitabine-based chemotherapy. Methods: The retrospective cohort of PC patients treated with gemcitabine between 2007 and 2016 was identified in the Polish National Health Fund databases. Electronic records of prescriptions were searched to identify in this cohort patients receiving CCB (amlodipine, nitrendipine, felodipine, lacidipine). The primary endpoint was OS and it was determined by Kaplan-Meier methods and compared by the log-rank test. Results: In total 4628 PC patients treated with gemcitabine (median OS 7.7 months; 95% CI: 7.4-7.9) were identified. Among these 380 patients were prescribed any CCB. There was a significant difference (p < 0.001) in median OS between patients prescribed CCB (n = 380; OS 9.3 months; 95% CI: 7.8-11.0) and those who did not (n = 4214; OS 7.6 months; 95% CI: 7.3-7.8) with hazard ratio for death 0.70 (95% CI: 0.62-0.79). Notably, the survival curves tended to flatten in CCB group, with 24% of patients alive at 2 years (95% CI: 20-29%) and 15% alive at 5 years (95% CI: 11-19%), compared with 11% (95% CI: 10-12%) and 4% (95% CI: 4-5%) in controls respectively. Conclusions: The use of CCB in PC patients receiving gemcitabine-based chemotherapy was associated with improved OS. Further validation is needed to evaluate effectiveness of CCB-gemcitabine combinations in the management of PC.

2014 ◽  
Vol 80 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Clancy J. Clark ◽  
Janani S. Arun ◽  
Rondell P. Graham ◽  
Lizhi Zhang ◽  
Michael Farnell ◽  
...  

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4484-4484
Author(s):  
Smith Giri ◽  
Nunnery Sara ◽  
Syed S. Nasir ◽  
Michael G Martin

Abstract Background: Limited data exists regarding the characteristics and outcomes of adolescents and young adults (AYAs) with acute myeloid leukemia (AML) which are largely under-represented in both pediatric and adult trials. We sought to compare the characteristics and outcomes of AYAs with AML using a large population based registry in the United States. Methods: We utilized Surveillance Epidemiology and End Results (SEER)-18 registry to identify all pediatric (0-18 years) and AYA (age 19-30 years) patients diagnosed with AML using appropriate histology codes based on the International Classification of Diseases for Oncology, 3rd version. Patients with acute promyelocytic leukemia (APL) were excluded from all analysis. Survival statistics were computed for each group using actuarial (Kaplan-Meier method) and compared using Z test for comparison of population proportions. Early mortality, defined as mortality within 1 month of diagnosis, was used as a surrogate for treatment related mortality. Kaplan Meier survival curves were plotted and compared using log-rank test. Multivariate analysis was done using logistic regression and Cox proportional hazard regression model. All p values were two sided and the level of significance was chosen at 0.05. Results: A total of 6343 eligible patients were identified, which comprised 2836 (44.7%) AYAs. A total of 52% (n=3346) were males, whereas 76%(n=4825) were whites. Histologically, majority of patients (56%; n=3545) were categorized as AML, not otherwise specified, followed by acute monocytic leukemia (9.9%, n=630). Majority (55%; n-3509) of the patients were diagnosed between 2001-2012. The early mortality rate was lower in the pediatric AML patients (pAML) as compared to AYAs (6.2% vs 9.2%; p<0.01). Similarly the 1 year (70.3% versus 62.1%; p <0.01) and 5 year (48.2% vs 36.4%; p<0.01) was higher in pediatric patients as compared to AYAs. Kaplan Meier plot showed worse overall survival of AYAs compared to pAMLs (Figure 1; p value of log rank <0.01). Multivariate logistic regression showed higher early mortality among AYAs as compared to pAML patients (OR 1.48; 95% CI 1.23-1.79; p<0.01). Similarly Cox regression showed worse overall survival among AYAs as compared to pAML (HR 1.34; 95% CI 1.26-1.44; p <0.01) Conclusions: Our population based analysis shows worse overall survival among AYAs as compared to pAML patients. Future clinical trials specifically focused on this age group are warranted to establish appropriate treatment regimens in this population. Figure 1. Kaplan Meier Survival curve showing cumulative survival among pediatric patients with AML as compared to AYAs. Log rank test showed statistically significant difference between the two curves (p value <0.01) Figure 1. Kaplan Meier Survival curve showing cumulative survival among pediatric patients with AML as compared to AYAs. Log rank test showed statistically significant difference between the two curves (p value <0.01) Disclosures No relevant conflicts of interest to declare.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18125-e18125
Author(s):  
Eduardo Richardet ◽  
Martin Eduardo Richardet ◽  
Nicolas Castagneris ◽  
Matias Nicolas Cortes ◽  
Perelli Laura ◽  
...  

e18125 Background: Platinum based regimens are standard first-line treatment in patients with advanced non mall cell lung cancer. We intend to evaluate their effectiveness according to the number of cycles administered, and investigate whether histology is a predictor of benefit from a greater number of infusions. Methods: 124 patients with stage IV NSCLC were evaluated retrospectively. They were divided according to whether they made 4 or 6 cycles of chemotherapy. The schemes used were: Cisplatin / Gemcitabine and Carboplatin / Paclitaxel, at standard doses. We studied the efficacy in both groups according to the most common histologies (adenocarcinoma and squamous cell carcinoma). PFS (progression-free survival) and OS (overall survival) were calculated by the Kaplan-Meier curves and compared by the Log Rank Test. Results: Those who underwent 4 cycles had a PFS of 7.77 months and OS of 12.2 months vs. 8.64 and 10.8 months those who received 6 cycles (p = 0.47, p = 0.76). Within the subgroup with squamous histology (n = 43), PFS and OS were 7.38 and 13.38 months respectively in the group that received 4 cycles vs. 7.97 and 9.76 months in those receiving 6 (p = 0.70, p = 0.32 ). Within adenocarcinoma histology (n = 81), those who received 4 cycle, has a PFS of 8.17 months and they lived 11.56 month, vs 8.96 and 10.79 months for those receiving 6 cycles (p = 0.29, p = 0.88) Conclusions: In our population, a greater number of cycles showed no advantages in terms of progression-free survival or overall survival. Histology is not a predictive factor for deciding how many chemotherapy cycles administer.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 378-378
Author(s):  
Talia Golan ◽  
Pascal Hammel ◽  
Michele Reni ◽  
Eric Van Cutsem ◽  
Teresa Macarulla ◽  
...  

378 Background: POLO is the first phase 3 trial to evaluate maintenance therapy with the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib (O) in patients with metastatic pancreatic cancer (mPaC) and a germline BRCA mutation ( gBRCAm) whose disease had not progressed on first-line platinum-based chemotherapy (PBC). POLO demonstrated that patients had significantly longer progression-free survival (PFS; primary endpoint) with maintenance O than with placebo (P; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.35–0.82; p= 0.004). Herein, we present final overall survival (OS) data. Methods: POLO was a randomized, double-blind, placebo-controlled trial (NCT02184195) conducted at 119 sites in 12 countries. Eligible patients had mPaC without disease progression for ≥16 weeks on PBC and a deleterious or suspected deleterious gBRCAm. Patients were randomized 3:2 to O (300 mg tablet twice daily) or P. OS (time from randomization until death) was a key secondary endpoint assessed using a log-rank test. A multiple-testing procedure (MTP) was used, with alpha passed to OS owing to a significant PFS result. Time from randomization to second disease progression or death (PFS2), to discontinuation of treatment (TDT), and to initiation of first (TFST) or second (TSST) subsequent therapies following treatment discontinuation or death were secondary endpoints (log-rank test, not in MTP). Primary analysis of OS after 108 deaths; data cut-off (DCO) July 21 2020. Results: Ninety-two and 62 patients were randomized to O and P, respectively; those censored had a median follow-up of 31.3 months (mo) and 23.9 mo, respectively. At DCO, n = 13 remained on O; n = 2 on P. OS was similar for the O and P groups (median 19.0 and 19.2 mo, respectively; HR 0.83 favoring O; 95% CI 0.56–1.22; p= 0.3487). OS at 36 mo was 33.9% for O and 17.8% for P. Median PFS2 was 16.9 mo for O vs 9.3 mo for P (HR, 0.66; 95% CI 0.43–1.02; p= 0.0613). TFST, TSST and TDT were longer with O than P (Table). TDT at 24 mo was 24.3% for O vs 3.3% for P; at 36 mo was 17.2% for O vs 3.3% for P. Incidence of grade ≥3 adverse events (AEs) was 49% for O (anemia most common [12.2%]); 25% for P (anemia, hyperglycemia, upper abdominal pain most common [3.3%]). Treatment was discontinued owing to AEs for 8.9% patients in the O arm vs 1.6% for P. Conclusions: Although HR for OS was in favor of maintenance O vs P among patients with a gBRCAm and mPaC whose disease had not progressed during PBC, there was no statistically significant difference. PFS2 showed a clear trend for treatment benefit beyond disease progression in favor of O, but was not alpha protected. Safety data were consistent with the primary analysis. Clinical trial information: NCT02184195. [Table: see text]


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrés Moreno Roca ◽  
Luciana Armijos Acurio ◽  
Ruth Jimbo Sotomayor ◽  
Carlos Céspedes Rivadeneira ◽  
Carlos Rosero Reyes ◽  
...  

Abstract Objectives Pancreatic cancers in most patients in Ecuador are diagnosed at an advanced stage of the disease, which is associated with lower survival. To determine the characteristics and global survival of pancreatic cancer patients in a social security hospital in Ecuador between 2007 and 2017. Methods A retrospective cohort study and a survival analysis were performed using all the available data in the electronic clinical records of patients with a diagnosis of pancreatic cancer in a Hospital of Specialties of Quito-Ecuador between 2007 and 2017. The included patients were those coded according to the ICD 10 between C25.0 and C25.9. Our univariate analysis calculated frequencies, measures of central tendency and dispersion. Through the Kaplan-Meier method we estimated the median time of survival and analyzed the difference in survival time among the different categories of our included variables. These differences were shown through the log rank test. Results A total of 357 patients diagnosed with pancreatic cancer between 2007 and 2017 were included in the study. More than two-thirds (69.9%) of the patients were diagnosed in late stages of the disease. The median survival time for all patients was of 4 months (P25: 2, P75: 8). Conclusions The statistically significant difference of survival time between types of treatment is the most relevant finding in this study, when comparing to all other types of treatments.


2018 ◽  
Vol 160 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Phoebe Kuo ◽  
Sina J. Torabi ◽  
Dennis Kraus ◽  
Benjamin L. Judson

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Allison Taylor ◽  
Kimberley Doucette ◽  
Bryan Chan ◽  
Xiaoyang Ma ◽  
Jaeil Ahn ◽  
...  

Introduction The literature suggests a widespread reduction in the availability and accessibility of newer treatment options among marginalized groups in AML. Studies from large national databases point to lower socio-economic status, Hispanic and African American race, Medicare or no insurance, being unmarried, treatment at non-academic centers, and rural residence as negatively impacting overall survival (OS) and rates of chemotherapy utilization in AML patients (Patel et al. 2015, Jaco et al. 2017, Bhatt et al. 2018, Master et al. 2016). We hypothesized that facility affiliation and pt volume would also have important effects on time to treatment (TTT) and OS in AML, even when these socioeconomic disparities were accounted for. Methods For this retrospective analysis, we used NCDB data that included 124,988 pts over the age of 18 with AML between the years 2004-2016. Variables analyzed included facility types described as community cancer programs (CP), comprehensive community cancer programs (CCP), academic/research center cancer programs (AC) and integrated network cancer programs (IN), and volume of facilities defined as high volume (HV) and low volume (LV). HV facilities had case volumes of ≥ 99th percentile and all other facilities were classified as LV. Multivariate analyses (MVA) included demographic and socioeconomic covariables. We used Cox proportional hazard analysis for both TTT and OS MVA. The Kaplan-Meier method was used to estimate median TTT and OS, and the log rank test used to compare TTT and OS across predictor variables. Results The median age of AML patients was 63 yrs (range 18-90) with 54% males, and 86% Caucasian. Five percent of patients were treated at CP, 30% at CCP, 44% at AC, and 10% at IN. 21% at HV facilities and 79% at LV facilities. Median TTT in days at CP facilities was 7, compared to 5 days in CCP and AC facilities versus 4 days at IN (p&lt;0.0001). TTT was 5 days at HV facilities versus 4 days at LV facilities (p&lt;0.0001). Kaplan-Meier curves showed that TTT was similar between HV and LV facilities(figure 1). The median OS was 3.25 months in CP compared to 4.34 months at CCP, 5.06 months at IN and 9.53 months at AC (p&lt;0.0001). For facility volume, the median OS was 13.11 months in HV facilities compared to 6.93 months in LV facilities (p&lt;0.0001). When sex, race, age, Hispanic Origin, education, urban/rural residence, Charlson-Deyo Comorbidity score and Great Circle Distance were adjusted for in MVA (table 1), the OS was higher in AC versus CP facilities (hazard ratio [HR] of 0.90 (0.87-0.93, p&lt;0.0001), and there was no statistically significant difference with comparison of other facility types to CP. Similarly, there was a lower OS at LV versus HV facilities with a HR of 1.14 (1.12-1.16, p&lt;0.0001). CCP facilities had a shorter TTT compared to CP with a HR of 1.21 (1.17-1.26, p&lt;0.0001). AC had a shorter TTT than CP with a HR of 1.17 (1.13-1.22, p&lt;0.0001), and IN had a shorter TTT compared to CP with a HR of 1.29 (1.24-1.34, p&lt;0.0001). Additionally, TTT in the MVA for facility volume was shorter in LV facilities compared to HV facilities with HR of 1.05 (1.04-1.07, p&lt;0.0001) [table 1]. Conclusion When adjusting for various socioeconomic factors, we found that TTT was longest in CP compared to CCP, AC, and IN. Treatment at a LV facility resulted in a decreased overall survival. LV facilities may be less familiar with treatment regimens for AML, less likely to use novel treatment options, and be less familiar with the disease. We showed that treatment at an AC compared to CP, CCP and IN facilities improved survival. Given poor outcomes for AML, these results show the importance of going to AC and HV facilities with more experience in treating AML for improved outcomes. Disclosures Lai: Astellas: Speakers Bureau; Jazz: Speakers Bureau; Abbvie: Consultancy; Agios: Consultancy; Macrogenics: Consultancy.


2016 ◽  
Vol 27 (4) ◽  
pp. 452-457 ◽  
Author(s):  
Gabrielle Branco Rauber ◽  
Jussara Karina Bernardon ◽  
Luiz Clovis Cardoso Vieira ◽  
Hamilton Pires Maia ◽  
Françoá Horn ◽  
...  

Abstract The aim of this study was to compare the fatigue resistance of restored teeth with bulk fill composite resin, conventional composite resin with incremental insertion and unprepared sound teeth. Twenty-eight extracted maxillary premolars were selected and divided into 4 groups based on composite resin and insertion technique: control (C), conventional composite resin with incremental insertion (I) and bulk fill composite resin with three (BF3) or single increment (BF1). The restored specimens were submitted to fatigue resistance test with a 5 Hz frequency. An initial application of 5,000 sinusoidal load cycles with a minimum force of 50 N and a maximum force of 200 N was used. Next, were applied stages of 30,000 load cycles with the maximum force increasing gradually: 400, 600, 800, 1000, 1200 and 1400 N. The test was concluded when 185,000 load cycles were achieved or the specimen failed. The fatigue resistance data were recorded for comparison, using the Kaplan-Meier survival curve and analyzed by log-rank test at 0.05 significance. Fractures were classified based on the position of the failure - above or below the cementoenamel junction (CEJ). Statistical analysis of the Kaplan-Meier survival curve and log-rank test showed a significant difference between groups (p=0.001). The fracture analysis demonstrated that only 28.58% of failures were below the CEJ in group C, while for groups I, BF1 and BF3 they were 42.85%, 85.71% and 85.71%, respectively. Teeth restored with composite bulk fill in both techniques present similar fatigue resistance values compared with those restored with a conventional incremental insertion of composite, while the fatigue strength values of unprepared sound teeth were higher. Furthermore, unprepared sound teeth showed a lower percentage of fractures below the CEJ.


Open Medicine ◽  
2008 ◽  
Vol 3 (3) ◽  
pp. 287-293
Author(s):  
Zorica Jovic ◽  
Vidojko Djordjevic ◽  
Karin Vasic ◽  
Snezana Cekic ◽  
Jankovic Irena

AbstractArterial hypertension and proteinuria are important factors associated with the progression of both diabetic and nondiabetic chronic kidney disease. The objective of the present study was to determine the influence of different antihypertensive drug groups on urinary albumin excretion (UAE) as related to blood pressure in non-diabetic population. Subjects (n=39) with chronic renal disease accompanied by mild to moderate hypertension and varying degrees of proteinuria were divided into 3 groups based on UAE values and placed on nonpharmacological and/or treatment with an antihypertensive drug regimen (consisting of one or more antihypertensive drugs [beta blocker, ACE inhibitor or calcium-channel blocker]) to achieve a target blood pressure ≤ 130/85 mmHg. Periodic UAE measurements were performed. A reduction was observed over time in most patients, however, it reached statistical significance only in the microalbuminuric group (P<0.01). Patients were further stratified into 5 groups depending on assigned therapy: 0, nonpharmacological treatment; 1-drug group 1; 12-drug groups 1 and 2; 13-drug groups 1 and 3; 123-all 3 drug groups (1-ACE inhibitors, 2-beta blockers, 3-calcium channel blockers). A statistically significant change in mean UAE values at the start and end of the study period in patients assigned to drug groups 12, 13, and 123 was achieved (P < 0.05). Also, there was a statistically significant difference in the average reduction of proteinuria under varying antihypertensive drug regimens (P < 0.05). In conclusion, in patients with hypertension, changes in UAE depend on initial UAE values and administered antihypertensive treatment. ACE inhibitors combined with calcium channel blockers resulted in a higher UAE reduction than other drug groups.


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