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Integrating COX-2 Inhibition with Chemoradiation for Rectal Cancer

Integrating COX-2 Inhibition with Chemoradiation for Rectal Cancer

HOUSTON—M. D. Anderson Cancer Center researchers have launched a phase I
trial combining pelvic radiation, irinotecan (Camptosar), and celecoxib
(Celebrex) in patients with metastatic rectal cancer. Christopher H. Crane, MD,
assistant professor of radiation oncology at the University of Texas M. D.
Anderson Cancer Center described the research leading up to this trial.

"Over the past 10 years we have treated patients with a program of
neoadjuvant chemoradiation with infusional 5-fluorouracil (5-FU), and we now
have nearly 400 patients who have been treated with a curative resection.
Patients who have a complete response to chemoradiation have improved local
control, improved survival, and sphincter preservation. We also have some
intriguing data suggesting that organ preserving is possible in selected
patients, and our interest in the potential benefits of adding cyclooxygenase-2
(COX-2) inhibition to the regimen is the hope that it will increase the number
of such patients," Dr. Crane, said.

Dr. Crane reported that both univariate and multivariate analyses of these
patients showed that those who had either a pathologic complete response or
only microscopic residual disease had significantly better local control and
overall survival.

Presents Difficult Problem

Low rectal cancer is a difficult problem because patients are concerned
about the potential need for colostomy. "When we stratified patients by
the distance of the tumor from the anal verge, and stratified them by whether
they had a complete response or an incomplete response, we found that patients
who had tumors in the very low rectum had a statistically significant
improvement in sphincter preservation. Response was independently significant
for sphincter preservation," Dr. Crane said.

Over the past decade the M. D. Anderson researchers have also treated 15 of
181 patients with T3 rectal tumors who had clinical complete response following
chemoradiation and then had full-thickness local excision.

"Local excision in T-3 patients is generally discouraged because of
high local recurrence rates, even with postoperative chemoradiation. Our cases
were mostly patients who refused radical surgery or were medically inoperable.
In this population of complete responders, we have had one pelvic nodal
recurrence, which occurred in a patient who in retrospect had imaging evidence
of a node in the pelvis. We have also had had one inguinal failure in a very
low lesion. The follow-up is a median 40 months (range 8 to 96), which is not
long enough to conclude anything, but this is certainly provocative data,"
Dr. Crane said. This raises the intriguing possibility that patients with
complete responses might be managed nonsurgically or with local excision.

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