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Can Concurrent Amifostine and 5-FU Permit Delivery of Higher Boost Doses of Radiation?

Can Concurrent Amifostine and 5-FU Permit Delivery of Higher Boost Doses of Radiation?

ST. LOUIS—Soon to be launched is a trial to determine if 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.

Acute Toxicity

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

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