Rationale for heparin treatment of colon cancer

SummaryIt is widely known that the systemic blood coagulation mechanism is often activated in malignancy, leading to an increased incidence of vascular thromboses in patients with cancer. It is not widely appreciated, however, that products of the coagulation mechanism may also support tumor growth and dissemination. Interest in this approach to cancer therapy has surged recently because of mounting evidence that the familiar anticoagulant drug, heparin, may impede tumor progression. Heparin has the capacity to modify angiogenesis, growth factor and protease activity, immune function, cell proliferation and gene expression in ways that may block malignant dissemination. Clinical trials in which heparin has been administered to a broad spectrum of patients to prevent or treat thrombosis have unexpectedly shown improvement in survival in the subset of patients with malignancy entered to these studies. Meta-analyses of clinical trials comparing unfractionated (UF) versus low molecular weight (LMW) heparin treating venous thromboembolism suggest that there may be substantial improvement in cancer outcome in patients with malignancy randomized to receive LMW heparin. These findings provide a rationale for definitive clinical trials of LMW heparin in cancer, and the results of several such studies that are currently underway are awaited with interest.

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Heparin and Cancer

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615131 ◽

1998 ◽

Vol 80 (07) ◽

pp. 10-23 ◽

Cited By ~ 104

Author(s):

Deborah Ornstein ◽

Leo Zacharski

Keyword(s):

Clinical Trials ◽

Unfractionated Heparin ◽

Cancer Progression ◽

Randomized Clinical Trials ◽

Molecular Forms ◽

Term Survival ◽

Human Malignancy ◽

Intensive Investigation ◽

Cancer Outcome ◽

Meta Analyses

SummaryHeparin has been the subject of intensive investigation for decades by both basic and clinical scientists because of its usefulness as a therapeutic anticoagulant (1). In addition to its effects on coagulation, however, heparin exhibits many other activities which seem to have little to do with anticoagulation (2). Goerner first observed an effect on the natural history of malignancy in 1930 when he demonstrated that heparin inhibited tumor growth in experimental animals (3). A substantial body of literature on heparin and cancer has developed during the ensuing decades. A recent increase in interest has resulted from observations made during prospective, randomized clinical trials which compared unfractionated heparin (UH) with low molecular weight heparin (LMWH) for the prevention and treatment of venous thromboembolism (VTE). Several studies have shown improvement in short to intermediate term survival in the subset of patients with cancer who received LMWH. This improved outcome has been emphasized in two published meta-analyses (4, 5), and the trend is supported by the results of a more recent prospective study (6). The improved cancer outcome could not be attributed to prevention of VTE in any of the studies; therefore, it is reasonable to hypothesize that a beneficial effect of heparin may be mediated by mechanisms independent of anticoagulation.Heparin has several properties that may plausibly explain its effect on experimental and human malignancy. The purpose of this paper is to summarize the literature on heparin and cancer and review mechanisms by which heparin may exert antineoplastic activity. The goal is to encourage both definitive clinical trials of heparin on cancer outcome and further studies of drug mechanisms in human malignancy. LMWH, with its favorable pharmacokinetic attributes, is suitable for chronic outpatient administration and is an excellent candidate for further investigation. Such a departure from conventional experimental cytotoxic chemotherapy holds promise for development of novel forms of growth regulatory therapy that interrupt pathways of cancer progression. In this review, “heparin” will refer to unfractionated heparin (UH), and “UH” and “LMWH” will be used to distinguish between the two molecular forms.

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Oncology Clinical Trials During the COVID-19 Pandemic

ONCOLOGY ◽

10.46883/onc.2020.3407.0265 ◽

2020 ◽

pp. 265-269

Author(s):

Aline Lara Gongora ◽

Denis Jardim ◽

Diogo Assed Bastos

Keyword(s):

Clinical Trials ◽

Mortality Rates ◽

Research Community ◽

Regulatory Agencies ◽

Patients With Cancer ◽

The Past ◽

Oncology Research ◽

Oncology Clinical Trials ◽

National Governments ◽

To Receive

The coronavirus disease 2019 (COVID-19) pandemic has rapidly spread all over the world in the past several months. No effective treatment for COVID-19 has been established. High transmissibility and considerable mortality rates have forced many national governments to implement quarantine measures. Many patients with cancer rely on clinical trials to receive their oncologic care, but the routine conduct of clinical trials has substantially changed because of the COVID-19 pandemic. The oncology research community should implement formal policies based on the guidance given from regulatory agencies, with the goal of minimizing the risks of COVID-19 infection while maintaining appropriate oncologic treatments for patients during this pandemic.

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L-arginine effect on inflammatory mediators: A systematic review of randomized controlled clinical trials

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000619 ◽

2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Seyed Reza Mirhafez ◽

Mitra Hariri

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Inflammatory Mediators ◽

Randomized Clinical Trials ◽

Randomized Controlled Clinical Trials ◽

Patients With Cancer ◽

Reactive Protein ◽

Randomized Controlled ◽

Human Adults ◽

Factor Α

Abstract. L-arginine is an important factor in several physiological and biochemical processes. Recently, scientists studied L-arginine effect on inflammatory mediators such as C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We conducted a systematic review on randomized controlled trials assessing L-arginine effect on inflammatory mediators. We searched data bases including Google scholar, ISI web of science, SCOPUS, and PubMed/Medline up to April 2019. Randomized clinical trials assessing the effect of L-arginine on inflammatory mediators in human adults were included. Our search retrieved eleven articles with 387 participants. Five articles were on patients with cancer and 6 articles were on adults without cancer. L-arginine was applied in enteral form in 5 articles and in oral form in 6 articles. Eight articles were on both genders, two articles were on women, and one article was on men. L-arginine could not reduce inflammatory mediators among patients with and without cancer except one article which indicated that taking L-arginine for 6 months decreased IL-6 among cardiopathic nondiabetic patients. Our results indicated that L-arginine might not be able to reduce selected inflammatory mediators, but for making a firm decision more studies are needed to be conducted with longer intervention duration, separately on male and female and with different doses of L-arginine.

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QoL, Cancer Outcome Linked in Meta-Analyses

Clinical Psychiatry News ◽

10.1016/s0270-6644(08)70504-6 ◽

2008 ◽

Vol 36 (7) ◽

pp. 53

Author(s):

KERRI WACHTER

Keyword(s):

Cancer Outcome ◽

Meta Analyses

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Treatment and secondary prevention of venous thromboembolism in cancer patients

Onkologische Welt ◽

10.1055/s-0038-1630173 ◽

2012 ◽

Vol 03 (03) ◽

pp. 121-125

Author(s):

I. Pabinger ◽

C. Ay

Keyword(s):

Clinical Trials ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Oral Anticoagulants ◽

Factor Xa ◽

New Oral Anticoagulants ◽

Phase Iii ◽

Patients With Cancer ◽

Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

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Low Molecular Weight Heparin Therapy: Is Monitoring Needed?

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648866 ◽

1994 ◽

Vol 72 (03) ◽

pp. 330-334 ◽

Cited By ~ 72

Author(s):

B Boneu

Keyword(s):

Molecular Weight ◽

Clinical Trials ◽

Plasma Proteins ◽

Bleeding Risk ◽

Heparin Therapy ◽

Low Molecular Weight ◽

Vein Thrombosis ◽

Meta Analyses ◽

Deep Vein ◽

Initial Check

SummaryRecent meta-analyses indicate that low molecular weight heparins (LMWH) are more effective than unfractionated heparin (UH) in preventing and treating deep vein thrombosis. This article presents the arguments for and against the need for laboratory monitoring. At the present time, the only tests currently available for monitoring LMWH therapy are those which measure the anti Xa activity in the plasma. Due to lower binding to plasma proteins and to cell surfaces,the plasma anti Xa activity generated by a given dose of LMWH is more predictable than for UH.Some clinical trials suggest that LMWH delivered at the recommended dose expose the patient to less bleeding risk than UH. Several . meta-analyses indicate comparable risk while any overdose unaccept-ably increases the haemorrhagic risk. The lowest dose of LMWH still effective in treating established DVT is presently unknown; some reports indicate that inadequate doses of LMWH are associated with a lack of efficacy for prevention. An overview of the published clinical trials indicates that the LMWH dose has never been monitored for prevention of DVT. In the treatment of established DVT, several trials have been performed without any monitoring, while in others the dose was adapted to target a given anti Xa activity. These considerations suggest that in prevention of DVT, monitoring the dose is not required. In the treatment of established DVT, considering the haemorrhagic risk of LMWH, the risk of undertreating the patient and the absence of large clinical trials comparing the advantages of monitoring the dose or not, it might be useful to check anti Xa activity at least once at the beginning of the treatment but the need for this initial check remains to be established. Because a large proportion of patients will be in the desired range, dose adjustments will be far less frequent than for UH.

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Clinical trials — the personal perspective of the research physician?

Annals of the Russian academy of medical sciences ◽

10.15690/vramn1356 ◽

2020 ◽

Vol 75 (3) ◽

pp. 256-263

Author(s):

Maria Y. Egorova ◽

Irina A. Shuvalova ◽

Olga I. Zvonareva ◽

Igor D. Pimenov ◽

Olga S. Kobyakova ◽

...

Keyword(s):

Clinical Trials ◽

Medical Care ◽

New Technologies ◽

Healthcare Providers ◽

Study Drug ◽

Well Being ◽

Personal Perspective ◽

Public And Private ◽

Factors Affecting ◽

To Receive

Background. The organization of clinical trials (CTs) requires the participation and coordination of healthcare providers, patients, public and private parties. Obstacles to the participation of any of these groups pose a risk of lowering the potential for the implementation of CTs. Researchers are a key human resource in conducting of CT. Their motivation for participation can have a significant impact on the recruitment and retention of patients, on the quality of the data collected, which determines the overall outcome of the study. Aims to assess the factors affecting the inclusion of Russian physicians-researchers in CT, and to determine their role in relations with patients-participants. Materials and methods. The study was organized as a part of the Russian multicenter face-to-face study. A survey was conducted of researchers from 10 cities of Russia (20172018). The participation in the survey for doctors was anonymous and voluntary. Results. The study involved 78 respondents. Most research doctors highly value the importance of research for science (4,84 0,39), society (4,67 0,46) and slightly lower for participating patients (4,44 0,61). The expectations of medical researchers are related to improving their financial situation and attaining new experience (n = 14; 18,18%). However, the opportunity to work with new technologies of treatment and diagnosis (n = 41; 52,56%) acted as a motivating factor. According to the questionnaire, the vast majority of research doctors (n = 29; 37,18%) believe that the main reason for patients to participate in CT is to receive quality and free medical care. The most significant obstacle to the inclusion of participants in CT was the side effects of the study drug (n = 38; 48,71%). Conclusions. The potential of clinical researchers in Russia is very high. The patient-participant acts for the research doctor as the subject of the study, and not the object, so the well-being of the patient is not indifferent to the doctor. However, the features of the functioning of our health care system form the motivation of doctors-researchers (additional earnings, professional self-development) and the way they perceive the motivation of patients (CT as an opportunity to receive quality medical care).

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The Efficacy of Anti-inflammatory Agents in the Prevention of Atrial Fibrillation Recurrences

Current Medicinal Chemistry ◽

10.2174/1389450121666200302095103 ◽

2020 ◽

Vol 28 (1) ◽

pp. 137-151

Author(s):

Homa Nomani ◽

Sara Saei ◽

Thomas P. Johnston ◽

Amirhossein Sahebkar ◽

Amir Hooshang Mohammadpour

Keyword(s):

Atrial Fibrillation ◽

Clinical Trials ◽

Therapeutic Option ◽

General Rule ◽

Promising Candidate ◽

Term Basis ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Meta Analyses ◽

Af Recurrence

: Several studies have indicated an association between inflammation and the recurrence of Atrial Fibrillation (AF), especially after ablation, which is a therapeutic option leading to local inflammation. On the other hand, each AF can lead to another AF, as a general rule. Thus, preventing recurrences of AF is extremely important for patient outcomes. In this paper, we attempted to review the effect of medicinal agents with anti-inflammatory properties on the prevention of AF recurrence. There are several randomized controlled trials (RCTs) and meta-analyses on the prevention of AF recurrence using agents with anti-inflammatory properties, which include steroids, colchicine, statins, and n-3 fatty acids (n-3 FA). Clinical trials evaluating the efficacy of anti-inflammatory drugs in preventing the recurrence of AF led to inconsistent results for corticosteroids, statins and n-3 FAs. These results may be related to the fact that inflammation is not the only factor responsible for triggering recurrences of AF. For example, the presence of structural, mechanical and electrical remodeling could potentially be the most important factors that trigger recurrences of AF but these factors have not been addressed in most of the reported studies. Therefore, future clinical trials are needed to compare the efficacy of anti-inflammatory drugs in AF patients with, or without other factors. For colchicine, a potent anti-inflammatory drug, there are limited studies. However, all the studies investigating colchicine in the context of AF were consistent and promising, especially when colchicine was used on a short-term basis following ablation in patients with paroxysmal AF. Therefore, colchicine could be a promising candidate for further clinical studies involving recurrent AF.

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