Intermittent use of amifostine during postoperative radiochemotherapy and acute toxicity in rectal cancer patients

Purpose: Amifostine has been shown to be able to reduce acute radiation tox icity if administered daily Drier to radiation during a course of a convent ionally fractionated radiotherapy. A disadvantage is the necessity of daily intravenous injection. We have used amifostin in patients undergoing adjuv ant radiochemotherapy for rectal cancer. Amifostine was administered only i n the first and fifth week of radiotherapy together with 5-FU chemotherapy. The objective was to determine whether the intermittent use of amifostine may be effective in reducing acute radiation toxicity. Patients and Methods: From September 1997 through October 1998, 30 patients with stage II/III rectal cancer under went postoperative radiochemotherapy at our department. All patients had undergone curative (R0) resection and received 50.4 Gy to the pelvis with a 3-field technique using a belly board followed by a boost of 5.4 Gy to the presacral space in conventional fract ionation with 1.8 Gy per fraction. 5-FU chemotherapy was administered as 12 0-hours continuous infusion in the first and fifth radiation week via a cen tral venous catheter in a daily dosage of 1 000 mg/m(2). All patients were offered to participate in a phase-II study using additional amifostine. Fif teen patients participated and received 500 mg amifostine daily on chemothe rapy days (days 1 to 5 and 29 to 33) immediately prior to the daily radiati on fraction. Fifteen patients did not participate and served as non-randomi zed control. The study was approved by the ethical committee of the Martin- Luther-University and informed consent was obtained from all patients. Results: The distribution of patients' characteristics and prognostic param eters was comparable in both groups. Side effects of amifostine were mild a nd included hypotension (53% grade I, 7% grade II) and nausea (47% grade I, 13% grade II). Antiemetics were not routinely used. All patients completed radiochemotherapy plus amifostine without unplanned breaks or dose reducti ons. One patient developed a cerebral infarction which was considered to be not related to the use of amifostine. As compared to the non-randomized co ntrol group, patients with additional amifostine had less acute skin and bo wel toxicity (maximum erythema score 1.47 +/- 0.64 without vs 0.87 +/- 0.52 with amifostine, p = 0.009 and maximum diarrhea score 1.07 +/- 1.03 vs 0.4 0 +/- 0.63, p = 0.044). Oral 5-FU-related mucositis and hematological toxic ity were not significantly different. Conclusions: In this phase-II study, amifostine significantly reduced acute skin and bowel toxicity of adjuvant chemoradiation in patients with rectal cancer even if the drug was administered only intermittently and not durin g the whole course of radiotherapy. This finding might be important with re gard to intense combined regimes and should be further investigated.