HOUSTONM. D. Anderson Cancer Center researchers have launched a phase I trial combining pelvic radiation, irinotecan(Drug information on irinotecan) (Camptosar), and celecoxib(Drug information on 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.