Kerr, David J., Dunn, Janet A., Langman, Michael J., Smith, Justine L., Midgley, Rachel S. J., Stanley, Andrew, Stokes, Joanne C., Julier, Patrick, Iveson, Claire, Duvvuri, Ravi and McConkey, Christopher C. (2007) Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. New England Journal Of Medicine , Vol.357 (No.4). pp. 360-369. doi:10.1056/NEJMoa071841

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Abstract

Background
Selective cyclooxygenase inhibitors may retard the progression of cancer, but they
have enhanced thrombotic potential. We report on cardiovascular adverse events in
patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer.
Methods
All serious adverse events that were cardiovascular thrombotic events were reviewed
in 2434 patients with stage II or III colorectal cancer participating in a randomized,
placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative
tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated
prematurely owing to worldwide withdrawal of rofecoxib. To examine possible
persistent risks, we examined cardiovascular thrombotic events reported up to 24
months after the trial was closed.
Results
The median duration of active treatment was 7.4 months. The 1167 patients receiving
rofecoxib and the 1160 patients receiving placebo were well matched, with a median
follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months
(27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events,
16 occurred in the rofecoxib group during or within 14 days after the treatment
period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards
model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet
Trialists’ Collaboration end point (the combined incidence of death from
cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction;
and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative
risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic
events, six in the rofecoxib group, were reported within the 2 years after trial
closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94;
P = 0.24). Four patients in the rofecoxib group and two in the placebo group died
from thrombotic causes during or within 14 days after the treatment period, and
during the follow-up period, one patient in the rofecoxib group and five patients in
the placebo group died from cardiovascular causes.
Conclusions
Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular
events among patients with a median study treatment of 7.4 months’ duration.
(Current Controlled Trials number, ISRCTN98278138.)

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Clinical trials, Colon (Anatomy) -- Cancer, Rofecoxib
Journal or Publication Title:	New England Journal Of Medicine
Publisher:	Massachusetts Medical Society
ISSN:	0028-4793
Official Date:	26 July 2007
Dates:	Date Event 26 July 2007 UNSPECIFIED
Volume:	Vol.357
Number:	No.4
Page Range:	pp. 360-369
DOI:	10.1056/NEJMoa071841
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Description:	Final version (published as open access)

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