Effect of low-molecular-weight heparin on survival in patients with advanced pancreatic adenocarcinoma

2007 ◽  
Vol 98 (08) ◽  
pp. 434-439 ◽  
Author(s):  
Muhammed Ayvaz ◽  
Stefan Wagenpfeil ◽  
Florian Eckel ◽  
Roland Schmid ◽  
Christian Lersch ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Overall Survival ◽  
Pancreatic Adenocarcinoma ◽  
Median Survival ◽  
Metastatic Disease ◽  
Hazard Ratio ◽  
Low Molecular Weight ◽  
Significant Difference ◽  
Chemotherapeutic Treatment ◽  
Advanced Pancreatic Adenocarcinoma

SummaryThis retrospective analysis aimed to identify whether low-molecular- weight heparins (LMWH) might improve survival in patients receiving chemotherapeutic treatment for advanced pancreatic adenocarcinoma.Two hundred forty-three patients who had received chemotherapy for advanced pancreatic adenocarcinoma were identified from a prospectively maintained database. Of these, 30 patients had to be excluded from analysis due to insufficient documentation. Of the remaining 213 patients 94 patients had been treated with LMWH, whereas 119 patients served as controls. Outcome was assessed in relation to overall survival, which was calculated from the date of initiation of chemotherapy to the date of death.There was no significant difference (hazard ratio, 0.8; 95% confidence interval (CI), 0.6 to 1.1; P=0,2) between the two groups in terms of overall survival. The median survival was 7.1 months (95% CI,5.8–8.4 months) in the LMWH group and 5.9 months (95% CI, 5.1–6.7 months) in the non-LMWH group. A positive effect of LMWH was seen in patients with metastatic disease (hazard ratio for LMWH vs. non-LMWH, 0,6; 95% CI, 0,4 to 0,8; P=0,006) in contrast to those without metastatic disease (hazard ratio for LMWH vs. non-LMWH, 1; 95% CI, 0.6 to 1.7; P=0,96).The median survival of patients with metastatic disease was 6,6 months (95% CI, 5–8,2 months) and 3.8 months (95% CI, 2.5–5.1 months) for the LMWH group and the non-LMWH group, respectively. In conclusion, we found for metastatic pancreatic adenocarcinoma a survival advantage for patients receiving LMWH. Nevertheless, our observations need confirmation by prospective randomized studies.

scholarly journals Anti-tumour effect of low molecular weight heparin in localised lung cancer: a phase III clinical trial

2018 ◽  
Vol 52 (4) ◽  
pp. 1801220 ◽  
Author(s):  
Guy Meyer ◽  
Benjamin Besse ◽  
Hélène Doubre ◽  
Anaïs Charles-Nelson ◽  
Sandro Aquilanti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Weight ◽  
Overall Survival ◽  
Low Molecular Weight Heparin ◽  
Stage I ◽  
Phase Iii ◽  
Low Molecular Weight ◽  
Significant Difference ◽  
Resected Stage ◽  
Iiia Nsclc

The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated.Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg−1 once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival.In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±sd age was 61.6±8.9 years, 190 (34.6%) patients had stage II−III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92–1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68–1.30; p=0.70).Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I−IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents.

The Effect of Low Molecular Weight Heparin on Survival in Patients With Advanced Malignancy

2005 ◽  
Vol 23 (10) ◽  
pp. 2130-2135 ◽  
Author(s):  
Clara P.W. Klerk ◽  
Susanne M. Smorenburg ◽  
Hans-Martin Otten ◽  
Anthonie W.A. Lensing ◽  
Martin H. Prins ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Life Expectancy ◽  
Median Survival ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Hazard Ratio ◽  
Low Molecular Weight ◽  
Double Blind Study ◽  
Advanced Malignancy

Purpose Studies in cancer patients with venous thromboembolism suggested that low molecular weight heparin may prolong survival. In a double-blind study, we evaluated the effect of low molecular weight heparin on survival in patients with advanced malignancy without venous thromboembolism. Methods Patients with metastasized or locally advanced solid tumors were randomly assigned to receive a 6-week course of subcutaneous nadroparin or placebo. The primary efficacy analysis was based on time from random assignment to death. The primary safety outcome was major bleeding. Results In total, 148 patients were allocated to nadroparin and 154 patients were allocated to placebo. Mean follow-up was 1 year. In the intention-to-treat analysis the overall hazard ratio of mortality was 0.75 (95% CI, 0.59 to 0.96) with a median survival of 8.0 months in the nadroparin recipients versus 6.6 months in the placebo group. After adjustment for potential confounders, the treatment effect remained statistically significant. Major bleeding occurred in five (3%) of nadroparin-treated patients and in one (1%) of the placebo recipients (P = .12). In the a priori specified subgroup of patients with a life expectancy of 6 months or more at enrollment, the hazard ratio was 0.64 (95% CI, 0.45 to 0.90) with a median survival of 15.4 and 9.4 months, respectively. For patients with a shorter life expectancy, the hazard ratio was 0.88 (95% CI, 0.62 to 1.25). Conclusion A brief course of subcutaneous low molecular weight heparin favorably influences the survival in patients with advanced malignancy and deserves additional clinical evaluation.

Randomized Comparison of Low Molecular Weight Heparin and Coumarin Derivatives on the Survival of Patients With Cancer and Venous Thromboembolism

2005 ◽  
Vol 23 (10) ◽  
pp. 2123-2129 ◽  
Author(s):  
Agnes Y.Y. Lee ◽  
Frederick R. Rickles ◽  
Jim A. Julian ◽  
Michael Gent ◽  
Ross I. Baker ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Solid Tumors ◽  
Metastatic Disease ◽  
Low Molecular Weight Heparin ◽  
Hazard Ratio ◽  
Low Molecular Weight ◽  
Coumarin Derivatives ◽  
Treatment Groups ◽  
Acute Venous Thromboembolism

Purpose Experimental studies and indirect clinical evidence suggest that low molecular weight heparins may have antineoplastic effects. We investigated the influence of a low molecular weight heparin dalteparin on the survival of patients with active cancer and acute venous thromboembolism. Patients and Methods Survival data were examined in a posthoc analysis in patients with solid tumors and venous thromboembolism who were randomly assigned to dalteparin or a coumarin derivative for 6 months in a multicenter, open-label, randomized, controlled trial. All-cause mortality at 12 months was compared between treatment groups in patients with and without metastatic malignancy. The effect of dalteparin on survival was compared between the two patient subgroups. Results During the 12-month follow-up period, 356 of 602 patients with solid tumors and acute venous thromboembolism died. Among patients without metastatic disease, the probability of death at 12 months was 20% in the dalteparin group, as compared with 36% in the oral anticoagulant group (hazard ratio, 0.50; 95% CI, 0.27 to 0.95; P = .03). In patients with metastatic cancer, no difference in mortality between the treatment groups was observed (72% and 69%, respectively; hazard ratio, 1.1; 95% CI, 0.87 to 1.4; P = .46). The observed effects of dalteparin on survival were statistically significantly different between patients with and without metastatic disease (P = .02). Conclusion The use of dalteparin relative to coumarin derivatives was associated with improved survival in patients with solid tumors who did not have metastatic disease at the time of an acute venous thromboembolic event. Additional studies are warranted to investigate these findings.

scholarly journals Comparison of FOLFIRINOX, Gemcitabine Plus Nab-Paclitaxel, and Chemoradiotherapy as First-Line Treatments for Locally Advanced Pancreatic Cancer

2021 ◽  
Author(s):  
Shintaro Nakano ◽  
Yoshito Komatsu ◽  
Yasuyuki Kawamoto ◽  
Rika Saito ◽  
Ken Ito ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Survival Rates ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Significant Difference ◽  
Locally Advanced Pancreatic Adenocarcinoma ◽  
Advanced Pancreatic Adenocarcinoma

Abstract Background: Currently, it is unclear whether chemotherapy or chemoradiotherapy (CRT) is the optimal first-line treatment for patients with locally advanced pancreatic adenocarcinoma. In this study, we compared the efficacy and safety of FOLFIRINOX (FFX), gemcitabine plus nab-paclitaxel (GnP), and CRT as first-line treatments for locally advanced pancreatic adenocarcinoma. Methods: We evaluated patients receiving FFX, GnP, or CRT, and assessed treatment efficacy in terms of overall survival and progression-free survival. Safety was evaluated using the Common Toxicity Criteria for Adverse Events (version 4.0). Results: Fifty-five patients were included in the analysis (10 for FFX, 25 for GnP, and 20 for CRT). The median overall survival was 7.1, 16.9, and 20.0 months in the FFX, GnP, and CRT groups, respectively. There was no significant difference in overall survival between the FFX and GnP groups (HR: 0.503, 95% CI: 0.205–1.238, p = 0.135), FFX and CRT groups (HR: 0.518, 95% CI: 0.213–1.256, p = 0.136), or GnP and CRT groups (HR: 0.993, 95% CI: 0.451–2.188, p = 0.987). The 1-year survival rates were 40%, 64%, and 60%, whereas the 2-year survival rates were 0%, 16%, and 35% in the FFX, GnP, and CRT groups, respectively. Conclusions: Both chemotherapy and CRT were effective and well tolerated. Thus, the combination of intensive chemotherapy and radiotherapy may be a beneficial treatment strategy.

scholarly journals Significance of indeterminate pulmonary nodules in resectable pancreatic adenocarcinoma—a review

2021 ◽  
Author(s):  
Li Lian Kuan ◽  
Ashley R. Dennison ◽  
Giuseppe Garcea
Keyword(s):  
Overall Survival ◽  
Pancreatic Adenocarcinoma ◽  
Median Overall Survival ◽  
Current Knowledge ◽  
Pulmonary Nodules ◽  
Preoperative Imaging ◽  
Significant Finding ◽  
Comprehensive Overview ◽  
Significant Difference ◽  
Clinical Dilemma

Abstract Background The clinical significance of indeterminate pulmonary nodules (IPN) in patients with resectable pancreatic adenocarcinoma (PDAC) is unknown. The rate of detection on IPN has risen due to enhanced staging investigations to determine resectability. IPNs detected on preoperative imaging represent a clinical dilemma and complicate decision-making. Currently, there are no recommendations on the management of IPN. This review provides a comprehensive overview of the current knowledge on the natural history of IPN detected among patients with resectable PDAC. Methods A systematic review based on a search in Medline and Embase databases was performed. All clinical studies evaluating the significance of IPN in patients with resectable PDAC were included. PRISMA guidelines were followed. Results Five studies met the inclusion criteria. The total patient population was 761. The prevalence of IPN reported ranged from 18 to 71%. The median follow-up duration was 17 months. The median overall survival was 19 months. Patients with pre-operative IPN which subsequently progressed to clinically recognizable pulmonary metastases, ranged from 1.5 to 16%. Four studies found that there was no significant difference in median overall survival in patients with or without IPNs. Conclusion This is a first review on the significance of IPN in patients with resectable PDAC. The preoperative presence of IPN does not demonstrate an association with overall survival after surgery. The identification of IPN is a significant finding however it should not preclude patients with resectable PDAC from undergoing curative resection.

PO-97 Overall survival with warfarin versus low-molecular-weight heparin in cancer-associated thrombosis

2021 ◽  
Vol 200 ◽  
pp. S72-S73
Author(s):  
R. Patell ◽  
T. Chiasakul ◽  
R. Redd ◽  
A.M. Khan ◽  
E.P. McCarthy ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Overall Survival ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Cancer Associated Thrombosis

scholarly journals Safety and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
N Hussain ◽  
S Adeel Hassan ◽  
S Mandava ◽  
F Yasmin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Efficacy And Safety ◽  
Dichotomous Data ◽  
Significant Difference

Abstract Funding Acknowledgements Type of funding sources: None. Background- Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been proven to be more effective in the management of venous thromboembolism (MVTE). The efficacy and safety of LMWH or DOACs in treatment of recurrent or malignancy induced VTE is not studied in literature. Objective To compare the efficacy and safety of LMWH and  DOACs in the management of malignancy induced  VTE Methods- Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to November  28th, 2020. Dichotomous data was extracted for prevention of VTE and risk of major bleeding in patients taking either LMWH or DOACs. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p < 0.05.  Results- Three studies with 2607 patients (DOACs n = 1301 ; LMWH n = 1306) were included in analysis. All the study population had active cancer of any kind diagnosed within the past 6 months. Average follow-up period for each trial was 6 months. Patients receiving DOACs have a lower odds of recurrence of MVTE as compared to LMWH( OR 1.56; 95% CI 1.17-2.09; P = 0.003, I2 = 0). There was no significant difference in major bleeding among patients receiving LMWH or DOACs  (OR-0.71, 95%CI 0.46-1.10, P = 0.13, I2 = 22%) (Figure 1). We had no publication bias in our results (Egger’s regression p > 0.05). Conclusion- DOACs are superior to LMWH in prevention of MVTE and have similar major bleeding risk as that of LMWH. Abstract Figure. A)VTE Recurrence B)Major Bleeding events

scholarly journals Effect of ageing on plasma lipoprotein(a) levels

2002 ◽  
Vol 39 (3) ◽  
pp. 237-240 ◽  
Author(s):  
Harukuni Akita ◽  
Miyao Matsubara ◽  
Hitoshi Shibuya ◽  
Hirotoshi Fuda ◽  
Hitoshi Chiba
Keyword(s):  
Molecular Weight ◽  
Coronary Heart Disease ◽  
Risk Factor ◽  
Heart Disease ◽  
The Elderly ◽  
Low Molecular Weight ◽  
Lipoprotein A ◽  
Significant Difference ◽  
The Mean ◽  
Japanese Subjects

Background Lipoprotein(a) [Lp(a)] is a risk factor for atherosclerosis and increases with age. The purpose of this study was to determine the effect of ageing on Lp(a) for three different apo(a) phenotypes. Methods We measured plasma Lp(a) concentrations in 551 unrelated Japanese subjects (20-88 years of age). We performed statistical analyses separately for three apo(a) phenotypes: the low-molecular-weight (LMW) phenotype with the F, B or S1 isoform, the intermediate-molecular-weight (IMW) phenotype with the S2 isoform and the high-molecular-weight (HMW) phenotype with the S3 or S4 isoform. Results For each phenotype, the mean plasma Lp(a) concentration and the frequency of Lp(a) concentrations ≥ 250 mg/L increased with age. Further, a statistically significant difference was always found between the younger subjects (20-39 years of age) and the elderly (over 60 years). The frequency of coronary heart disease increased with age, particularly for the LMW and IMW phenotypes. Conclusions We conclude that ageing elevates plasma Lp(a) concentrations, which may have a role in the prevalence of coronary heart disease in the elderly, especially those with the LMW or IMW phenotypes.

scholarly journals Outcomes of Patients with Initially Locally Advanced Pancreatic Adenocarcinoma who did not Benefit from Resection: A Prospective Cohort Study

2020 ◽  
Author(s):  
Jonathan Garnier ◽  
Jacques Ewald ◽  
Ugo Marchese ◽  
Marine Gilabert ◽  
Simon Launay ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Pancreatic Adenocarcinoma ◽  
Metastatic Disease ◽  
Performance Status ◽  
Locally Advanced ◽  
Wilcoxon Test ◽  
Stepwise Logistic Regression ◽  
Short Term Treatment ◽  
Locally Advanced Pancreatic Adenocarcinoma ◽  
Advanced Pancreatic Adenocarcinoma

Abstract Background: The current study aimed to evaluate the outcomes of patients with unresectable non-metastatic locally advanced pancreatic adenocarcinoma (LAPA) who did not benefit from resection considering the treatment strategy in the clinical settings. Methods: Between 2010 and 2017, a total of 234 patients underwent induction chemotherapy for LAPA that could not be treated with surgery. After oncologic restaging, continuous chemotherapy or chemoradiation (CRT) was decided for patients without metastatic disease. The Kaplan–Meier method was used to determine overall survival (OS), and the Wilcoxon test to compare survival curves. Multivariate analysis was performed using the stepwise logistic regression method. Results: FOLFIRINOX was the most common induction regimen (168 patients, 72%), with a median of 6 chemotherapy cycles and resulted in higher OS, compared to gemcitabine (19 vs. 16 months, hazard ratio (HR)=1.2, 95% confidence interval: 0.86–1.6, P =.03). However, no difference was observed after adjusting for age (≤75 years) and performance status score (0–1). At restaging, 187 patients (80%) had non-metastatic disease: CRT was administered to 126 patients (67%) while chemotherapy was continued in 61 (33%). Patients who received CRT had characteristics comparable to those who continued with chemotherapy, with similar OS. They also had longer progression-free survival (median 13.3 vs. 9.6 months, HR=1.38, 95% confidence interval: 1–1.9, P <.01) and limited short-term treatment-related toxicity. Conclusions: The median survival of patients who could not undergo surgery was 19 months. Hence, CRT should not be eliminated as a treatment option and may be useful as a part of optimised sequential chemotherapy for both local and metastatic disease.

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