Aim: We evaluated the feasibility and efficacy of postoperative hypofractionated and accelerated radiotherapy supported with amifostine cytoprotection (HypoARC) in patients with high-risk or recurrent prostate cancer.
Patients and methods: Fourty-eight patients were recruited (median follow-up=41 months; range=12-84 months). Twenty-one received HypoARC after surgery and 27 at biochemical relapse. Radiotherapy was given with a 3D-conformal technique, delivering 2.7 Gy/day to the pelvis and 3.4 Gy to the peri-prostatic region for 14 fractions. A 15th fraction increased the total dose to the peri-prostatic area to 51 Gy (15×3.4 Gy) in 19 days. Amifostine was delivered before each radiotherapy fraction at an individualized (by tolerance) dose (0-1000 mg).
Results: Amifostine was delivered subcutaneously at 1000 mg in 35/48 (72.9%) patients, while lower doses were tolerated by the remaining patients. Twenty-six (54.2%) patients accomplished therapy without delays, while acute toxicities enforced 1 to 2 week delays in 11/48 patients (22.9%). Grade 2 proctitis was noted in 18.7%, while substantial bleeding occurred in 8.3% of patients. Grade 1 dysurea was noted in 27.1%, while diarrhea grade 2 appeared in 10.4% of patients. High amifostine dose was linked to a significant reduction of proctitis (p=0.04). No severe late toxicities were noted. Within a median of 41 months, 7/48 (14.6%) patients exhibited post-radiotherpy biochemical failure (in four due to metastasis). High-dose (1000 mg) amifostine defined a significantly better outcome (p=0.004), an effect sustained on multivariate analysis.
Conclusion: Postoperative HypoARC is feasible with low-grade early and late toxicities, and emerges as a candidate for evaluation in randomized trials. The three-fold reduction of the overall treatment time renders HypoARC appealing for busy radiotherapy departments.