Preoperative Chemoradiation and Aggressive Surgery Effective in Locally Advanced Rectal Cancer

HOUSTON—Preoperative chemoradiation and aggressive surgery produced good local disease control and sphincter preservation in patients with locally advanced rectal cancer treated at the University of Texas M.D. Anderson Cancer Center, Houston, but more effective systemic therapy is needed, according to Christopher H. Crane, MD. Dr. Crane, who is assistant professor of radiation oncology at M.D. Anderson, reviewed data from 392 patients with stage II or stage III rectal cancer treated there over the past decade.

Standard adjuvant therapy was continuous infusion fluorouracil (5-FU) at 300 mg/m² given Monday through Friday with 45 Gy of radiation and mesorectal excision. Standard postoperative adjuvant chemoradiation includes 4 months of 5-FU-based systemic therapy plus pelvic chemoradiotherapy.

Sphincter Preservation

"The surgical principles for the management of rectal carcinoma at our institution involve resection of the primary tumor with margins of normal tissue around the tumor site, total mesorectal excision, and reconstruction. For tumors above 6 cm from the anal verge, the standard is low anterior resection with resection of the mesorectum well below the site of the tumor," Dr. Crane said.

"Over time there has been an increase in sphincter-preserving operations, which could have resulted from a change in either surgical techniques or attitudes," he noted. "There had been concern that improving sphincter preservation would lead to increased local recurrence, but local control has remained about 90%, so that has not been the case."

Dr. Crane said that preliminary data suggest that patients that have a pathologic complete response to preoperative chemoradiotherapy might be candidates for less extensive surgery, but this needs to be studied further. Studies of capecitabine (Xeloda) plus radiation therapy are also ongoing.

Managing Acute Effects

Dr. Crane said that supportive care is the key to the good results obtained at M.D. Anderson. "Preoperative chemoradiation is rarely interrupted due to acute toxicity," he noted.

"The common acute effects of pelvic chemoradiation are managed with aggressive outpatient supportive care," he continued. "The judicious use of prophylactic antiemetics and a three-step plan to manage diarrhea are used. The goal is to keep the frequency of bowel movements to fewer than four per day. Patients are initially instructed to take diphenoxylate and atropine (Lomotil) as needed. When that is no longer sufficient to control the increased frequency of bowel movement, patients take two Lomotil tablets every 3 to 4 hours. The third step is that loperamide (Imodium, Kaopectate II) is added and alternated with Lomotil: two tablets of one or the other are taken every 2 to 3 hours. We also use delayed and immediate-response narcotics. A recent analysis of patients on a trial of concomitant boost radiation indicated that this regimen was effective in preventing severe diarrhea."

Another common acute problem is desquamation of the perineal skin and genitalia after irradiation of low rectal lesions. Dr. Crane said that these reactions can be effectively managed with a lanolin-containing barrier cream in the perianal area, anusol suppositories for anal canal pain, and Aquaphor for the anterior skin reactions. Moist desquamation often requires narcotic pain medication, sitz baths, and the use of a hydrogel dressing.

Dr. Crane also reported that clinicians at his institution are sometimes re-irradiating patients that have had radiation therapy more than 1 year before. "We give smaller radiation doses bid with either capecitabine or 5-FU," he said.

Patients with rectal cancer who present with metastases are treated with radiation therapy upfront as 35 Gy in 14 fractions with concurrent capecitabine or 5-FU. "The one thing we want to avoid is painful progression in the pelvis, and we feel that patients should receive radiation therapy before they develop such progression," Dr. Crane said.