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LETTER TO THE EDITOR
Year : 2012  |  Volume : 8  |  Issue : 3  |  Page : 464

Three concerns with regards to the utilization of COX-2 inhibitor (celecoxib) in combination with standard chemoradiotherapy for nasopharyngeal carcinoma


Department of Radiation Therapy and Oncology, Regional Cancer Centre, Indira Gandhi Medical College, Shimla, India

Date of Web Publication17-Nov-2012

Correspondence Address:
Swaroop Revannasiddaiah
Department of Radiation Therapy and Oncology, Regional Cancer Centre, IGMC, Shimla, Himachal Pradesh - 171001
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.103540

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How to cite this article:
Revannasiddaiah S, Gupta M, Seam R, Rastogi M. Three concerns with regards to the utilization of COX-2 inhibitor (celecoxib) in combination with standard chemoradiotherapy for nasopharyngeal carcinoma. J Can Res Ther 2012;8:464

How to cite this URL:
Revannasiddaiah S, Gupta M, Seam R, Rastogi M. Three concerns with regards to the utilization of COX-2 inhibitor (celecoxib) in combination with standard chemoradiotherapy for nasopharyngeal carcinoma. J Can Res Ther [serial online] 2012 [cited 2019 Nov 20];8:464. Available from: http://www.cancerjournal.net/text.asp?2012/8/3/464/103540

Sir,

We read the article titled 'Efficacy and safety of concurrent chemoradiation with weekly cisplatin ± low-dose celecoxib in locally advanced undifferentiated nasopharyngeal carcinoma: A Phase II-III clinical trial'- published in the JCRT (October-December 2011). [1] Though we are appreciative of the investigators' intention to improve outcomes by the use of cyclooxygenase-2 (COX-2) inhibiting agent celecoxib as a radiosensitizer with chemoradiotherapy, we have to express three of our concerns regarding the study.

Our first concern is that the investigators have not provided any information regarding the utilization of analgesics for the management of inevitable side-effects of chemoradiation such as painful mucositis and odynophagia. It is often a common practice to utilize analgesics (non-narcotics, narcotics or a combination) for these therapy-induced painful symptoms. Chemically, non-narcotic analgesics are non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs by virtue of their pharmacology are cyclooxygenase (COX) inhibitors, with varying selectivity for COX-1 and COX-2 enzymes. [2] The investigators have not mentioned any information as to whether there were any restraints on the utilization of NSAIDs among the patients enrolled in their study. A good study design would have ensured that no NSAID would be utilized for the management of painful symptoms such as mucositis and odynophagia within the study protocol, since all NSAIDs inhibit COX-1 and 2 to varying degrees. [2]

The second issue of concern is regarding the confounding utilization of steroids as part of the management of chemoradiation-induced toxicities. The investigators have stated that steroids were utilized during the pre-medication phase prior to chemotherapy infusion. Since steroids too are inhibitors of COX,[3] their utilization has been another confounder in this study.

The third concern is rather serious. Celecoxib is associated with increased risks of cardiovascular events such as myocardial-infarction and stroke.[4] An ideal study design should state this specific risk before enrolment and prior to consent procurement (ethically). As a matter of fact, celecoxib had been tried in a large prematurely terminated trial (APC trial: 'adenoma prevention with celecoxib' trial) which had to be prematurely terminated due to an increase in cardiovascular mortality.[5]

We provide a hint of caution to future investigators attempting to utilize celecoxib in radiotherapy-related protocols so that a proper study design minimizing confounders may be designed and adopted. We also inform the reader about the cardiovascular risks associated with celecoxib, lest there be an increase in cardiovascular toxicities which could affect survival.

 
 > References Top

1.Mohamma-Dianpanah M, Razmjou-Ghalaei S, Shafizad A, Ashouri-Taziani Y, Khademi B, Ahmadloo N, et al . Efficacy and safety of concurrent chemoradiation with weekly cisplatin ± low-dose celecoxib in locally advanced undifferentiated nasopharyngeal carcinoma: A phase II-III clinical trial. J Can Res Ther 2011;7:442-7.  Back to cited text no. 1
    
2.Hawkey CJ. COX-2 inhibitors. Lancet 1999;353:307-14.  Back to cited text no. 2
    
3.Goppelt-Struebe M, Wolter D, Resch K. Glucocorticoids inhibit prostaglandin synthesis not only at the level of phospholipase A2 but also at the level of cyclo-oxygenase/PGE isomerase. Br J Pharmacol 1989;98:1287-95.  Back to cited text no. 3
    
4.Solomon SD, Wittes J, Finn PV, Fowler R, Viner J, Bertagnolli MM, et al . Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation 2008;117:2104-13.  Back to cited text no. 4
    
5.Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, et al . Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005;352:1071-80.  Back to cited text no. 5
    



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