ST. LOUISSoon to be launched is a trial to determine if amifostine(Drug information on amifostine) (Ethyol) with concurrent infusion of 5-fluorouracil will permit delivery of higher boost doses of radiation in unresectable or locally recurrent rectal cancer.
"Although many patients are cured with a combination of preoperative radiation and surgery, less than 10% achieve a complete response to radiation, and only about 10% to 30% show a complete response to chemotherapy and radiation," said Robert J. Myerson, MD, PhD, explaining the rationale for the trial. "Patients who might benefit from higher preoperative radiation doses include those with locally advanced cancers and unresectable cancers, recurrent cancers, or distal tumors (to facilitate sphincter preservation)." Dr. Myerson is professor of radiology at Washington University School of Medicine in St. Louis.
One strategy to improve response is to increase radiation dose. With concurrent chemotherapy, however, the rectal and small bowel tolerance limits the rectal dose to about 55 Gy, according to Dr. Myerson. "The hope is that a radioprotectant may permit dose intensification," he said.
"Acute toxicity in rectal cancer during preoperative chemoradiotherapy is substantial enough to be a useful endpoint in a radioprotectant trial," he noted. "With preoperative radiotherapy alone, the grade 3 or 4 acute rectal or small bowel toxicity rate is less than 10%. It rises to 20% to 30% with combined chemotherapy and radiation. Perioperative toxicity and late toxicity are both 10% to 15% with or without chemotherapy.
Dr. Myerson said that with most regimens of preoperative radiation, generally about 45 Gy, and 5-FU based regimens, acute grade 3 or worse morbidity occurs in 20% to 49% of patients. "The pathologic complete response for chemotherapy and radiation is better than with radiation alone, but it is still only about 30%. That’s not high enough to avoid proctectomy in most cases," he said.
Addition of Amifostine