Coxibs: Pharmacology, Toxicity and Efficacy in Cancer Clinical Trials

  • Luis A. Garcia Rodriguez
  • Lucia Cea-Soriano
  • Stefania Tacconelli
  • Paola Patrignani
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 191)


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.


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.



Acute myocardial infarction






Central nervous system


Colorectal cancer




European medicine agency


European union


Familial adenomatous polyposis


Food and drug administration








Randomized clinical trial


Relative risk


Rheumatoid arthritis




Traditional nonsteroidal anti-inflammatory drug


United States



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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