Designing a clinical trial of non-steroidal anti-inflammatory drugs for cancer pain: a survey of UK palliative care physicians

ObjectivesInsufficient quality evidence exists to support or refute the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the management of cancer pain. We aimed to determine the most clinically pragmatic design of a future randominsed controlled trial (RCT), based on how NSAIDs are currently used and perceived efficacy.MethodsAn online survey was distributed to members of the Association for Palliative Medicine of Great Britain and Ireland examining NSAID use, indications and perceived efficacy, as well as duration of respondents’ experience in palliative medicine.Results23% of 968 members responded. A placebo-controlled trial of NSAIDs as a strong opioid adjunct in cancer-related bone pain was considered the most clinically pragmatic design. Concerning current practice, oral administration was the preferential route (79.4%), dosed regularly (79.5%). Selective cyclooxygenase-2 (COX-2) inhibitors and non-selective COX-2 inhibitors were considered similarly effective by 45% in cancer pain; ibuprofen being the first line oral NSAID of choice (42.6%). Treatment efficacy is generally determined within 1 week (94.3%). On a Likert scale, most physicians consider NSAIDs improve cancer pain either ‘sometimes’ (57.7%) or ‘often’ (40%). Years of specialist palliative care experience did not affect perception of efficacy (p=0.353).ConclusionsA randomised controlled trial of NSAIDs as opioid adjuncts for cancer-related bone pain would be the most pragmatic design supported by palliative care clinicians to benefit clinical practice.

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The role of celecoxib as a potential inhibitor in the treatment of inflammatory diseases - a review

Current Medicinal Chemistry ◽

10.2174/0929867328666210910125229 ◽

2021 ◽

Vol 28 ◽

Author(s):

Josiane Viana Cruz ◽

Joaquín María Campos Rosa ◽

Njogu Mark Kimani ◽

Silvana Giuliatti ◽

Cleydson Breno Rodrigues dos Santos

Keyword(s):

Side Effects ◽

Inflammatory Diseases ◽

Structural Basis ◽

Potential Inhibitor ◽

Cyclooxygenase 1 ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors

: This article presents a simplified view of celecoxib as a potential inhibitor in the treatment of inflammatory diseases. The enzyme cyclooxygenase (COX) has, predominantly, two isoforms called cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The former plays a constitutive role that is related to homeostatic effects in renal and platelets, while the latter is mainly responsible for induction of inflammatory effects. Since COX-2 plays an important role in the pathogenesis of inflammatory diseases, it has been signaled as a target for the planning of anti-inflammatory intermediates. Many inhibitors developed and planned for COX-2 inhibition have presented side effects to humans, mainly in the gastrointestinal and/or cardiovascular tract. Therefore, it is necessary to design new potential COX-2 inhibitors, which are relatively safe and without side effects. To this end, of the generation of non-steroidal anti-inflammatory drugs from “coxibs”, celecoxib is the only potent selective COX-2 inhibitor that is still commercially available. Thus, the compound celecoxib became a commercial prototype inhibitor for the development of anti-inflammatory agents for COX-2 enzyme. In this review, we provide highlights where such inhibition should provide a structural basis for the design of promising new non-steroidal anti-inflammatory drugs (NSAIDs) which act as COX-2 inhibitors with lesser side effects on the human body.

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Nonsteroidal Anti-inflammatory Drugs and the COX-2 Inhibitors

Pain Review ◽

10.1016/b978-1-4160-5893-9.00343-9 ◽

2009 ◽

pp. 630-634

Author(s):

Steven D. Waldman

Keyword(s):

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors

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Nonsteroidal Anti-inflammatory Drugs, Acetaminophen, and COX-2 Inhibitors

Practical Management of Pain ◽

10.1016/b978-0-323-08340-9.00040-2 ◽

2014 ◽

pp. 553-568.e5 ◽

Cited By ~ 2

Author(s):

Brian Birmingham ◽

Asokumar Buvanendran

Keyword(s):

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors

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Nonsteroidal Anti-Inflammatory Drugs: A Potential Pharmacological Treatment for Intracranial Aneurysm

Cerebrovascular Diseases Extra ◽

10.1159/000499077 ◽

2019 ◽

Vol 9 (1) ◽

pp. 31-45 ◽

Cited By ~ 3

Author(s):

Courtney L. Fisher ◽

Stacie L. Demel

Keyword(s):

Nuclear Factor Κb ◽

High Morbidity ◽

Surgical Interventions ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Factor Α ◽

Wall Sheer Stress ◽

Cox 2 Inhibitors

Background: Saccular intracranial aneurysms (IAs) are outpouchings of the vessel wall of intracranial arteries. Rupture of IAs results in subarachnoid hemorrhage which is associated with high morbidity and mortality. Surgical interventions, such as clipping and coiling, have associated risks. Currently, there are no proven pharmacological treatments to prevent the growth or rupture of IAs. Infiltration of proinflammatory cytokines in response to increased wall sheer stress is a hallmark of IA. Nonsteroidal anti-inflammatory drugs (NSAIDs) are being investigated as potential therapeutic agents for reduction in growth and/or prevention of IA through inhibition of inflammatory pathways. Summary: This review will discuss the role of NSAIDs in attenuating the inflammation that drives IA progression and rupture. There are two main subtypes of NSAIDs, nonselective COX and selective COX-2 inhibitors, both of which have merit in treating IA. Evidence will be presented which shows that NSAIDs inhibit several key inflammatory mediators involved in IA progression including nuclear factor-κB, tumor necrosis factor-α, and matrix metalloproteinases. In addition, the role of NSAIDs in limiting inflammatory cell adhesion to endothelial cells and attenuating endothelial cell senescence will be discussed. Key Messages: There is an abundance of basic science and preclinical data that support NSAIDs as a promising treatment for IA. Additionally, a combination treatment strategy of low-dose aspirin given concomitantly with a selective COX-2 inhibitor may result in a reduced side effect profile compared to aspirin or selective COX-2 inhibitor use alone. Several large clinical trials are currently planned to further investigate the efficacy of NSAIDs as an effective nonsurgical treatment for IAs.

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