DETROIT—Intrarectal topical application of amifostine(Drug information on amifostine) (Ethyol), given as a "mini-enema," is extremely tolerable, produces no systemic toxicity, and may be an alternative to systemic administration for preventing rectal damage in patients undergoing radiotherapy for prostate cancer. Results of a phase I study were reported by Edgar Ben-Josef, MD. He is associate professor in the Department of Radiation Oncology at Wayne State University’s Karmanos Cancer Institute in Detroit.
"With 3D conformal treatment planning, it is possible to substantially reduce grade 3 toxicity, but at doses in the vicinity of 75 Gy, 15% to 25% of patients will still develop grade 2 or higher rectal toxicity," Dr. Ben-Josef explained. "With conventional, nonconformal radiotherapy, the rate of grade 3 or 4 late rectal complications is up to 10%."
Adding shielding can keep the dose to the anterior rectal wall less than 75.6 Gy and reduce grade 2 or higher rectal toxicity to 7%, according to Dr. Ben-Josef. The problem is that also risks shielding tumor tissue from therapeutic dosages.
"With that problem in mind, in 1998 we started a phase I study using a topical, intrarectal application to attempt to protect the rectum from radiation effects. The major objective was to evaluate the feasibility of an intrarectal application of amifostine. We were not sure if patients could tolerate and hold the mini-enema," Dr. Ben-Josef said.
The trial was also intended to determine the maximum tolerated dose (MTD) of intrarectal amifostine, to characterize the pharmacokinetics of intrarectal application, and to gather some data regarding efficacy.
Study Design
Amifostine was given as an aqueous solution 30 minutes before treatment during the first 15 days of radiotherapy. Dose escalation was from 500 mg to 2,500 mg in 500-mg cohorts. Pharmacokinetics assessments were done on days 1 and 10 of radiotherapy to see if changes in systemic absorption were induced by changes in the rectum wall secondary to radiotherapy, such as inflammation.
