Coxibs: Pharmacology, Toxicity and Efficacy in Cancer Clinical Trials

Chapter
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 191)

Abstract

This chapter briefly summarizes the current knowledge about the role of nonsteroidal anti-inflammatory drugs (NSAIDs), specially focusing on those selective for cyclooxygenase (COX)-2 (coxibs), on colorectal cancer (CRC) onset, and progression. Both epidemiological and experimental studies have reported that these drugs reduce the risk of developing colonic tumors. However, the promising use of coxibs in chemoprevention was halted abruptly due to the detection on enhanced cardiovascular (CV) risks. Thus, we discuss the clinical data and plausible mechanisms of CV hazards associated with traditional NSAIDs and coxibs. The extent of inhibition of COX-2-dependent prostacyclin, an important vasoprotective and anti-thrombotic pathway, in the absence of a complete suppression of COX-1-dependent platelet function, at common doses of NSAIDs, might play a role in CV toxicity. Coxibs might still be reserved for younger patients with familial adenomatous polyposis (FAP). However, it should be taken into consideration that recent findings of enhanced thromboxane (TX)A2 biosynthesis in colon tumorigenesis, detected in humans. In this context, the use of low-dose aspirin (which mainly acts by inhibiting platelet COX-1-dependent TXA2) may have a place for chemoprevention of CRCs (see also  Chap. 3). The possible use of coxibs to prevent CRC will depend mainly on research progresses in biomarkers able to identify the patients uniquely susceptible to developing thrombotic events by inhibition of COX-2.

Keywords

European Union Familial Adenomatous Polyposis Colorectal Adenoma Nonselective NSAID Cholesteryl Ester Hydrolase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AMI

Acute myocardial infarction

ASA

Aspirin

CV

Cardiovascular

CNS

Central nervous system

CRC

Colorectal cancer

COX

Cyclooxygenase

EMA

European medicine agency

EU

European union

FAP

Familial adenomatous polyposis

FDA

Food and drug administration

GI

Gastrointestinal

PGI2

Prostacyclin

PG

Prostaglandin

RCT

Randomized clinical trial

RR

Relative risk

RA

Rheumatoid arthritis

TXA2

Thromboxane

tNSAID

Traditional nonsteroidal anti-inflammatory drug

US

United States

Notes

Acknowledgments

This work was supported by research founding from the European Community Sixth Framework Programme (Eicosanox grant LSMH-CT-2004-005033). We apologize to our colleagues for not being able to reference all primary work due to space limitations.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Centro Español de Investigacion Farmacoepidemiologica (CEIFE)28004 MadridSpain
  2. 2.Center of Excellence On Aging (CeSI) and Department of Neuroscience and ImagingG. d’Annunzio University, School of Medicine66100 Chieti CHItaly

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