Treatment of invasive bladder cancer with conformal hypofractionated accelerated radiotherapy and amifostine (HypoARC)

Abstract

Introduction: Radiotherapy (RT) for bladder cancer is as an effective alternative of cystectomy. Although rapid cancer clonogen repopulation contributes to radio-resistance, accelerated RT schemes based on ≤ 2 Gy fractions have failed to improve results. We suggest that accelerated hypofractionation (HypoARC) may be more effective, as it targets both tumors with increased clonogenic activity and tumors with low radio-sensitivity.

Patients and methods: Eighty-two bladder cancer patients were treated with concomitant-boost conformal RT (14 × 2.7 Gy to the pelvis and 15 × 3.4 Gy to the bladder, within 19 days). Patients received a daily dose of 0/500/750/1,000 mg of amifostine using a dose-individualization algorithm (15.8%, 8.5%, 19.5%, and 56.1% of patients respectively).

Results: Early frequency grade 2-3, dysuria grade 1-2, diarrhea grade 2, and proctitis grade 2 appeared in 10.9%, 15.8%, 8.5%, and 13.4% of patients, respectively. The incidence of late sequelae was low (1.2% grade 2 frequency, 2.4% grade 2-3 dysuria, 2.4% grade 2-3 hematuria, 2.4% grade 2-3 incontinence). Patients receiving 1,000 mg of amifostine experienced significantly lower toxicities. The complete response rate, 3-year local control and disease specific survival rates were 86.6%, 56%, and 63%, respectively.

Conclusions: HypoARC is linked with low early and late radiation toxicity, which is further reduced with the administration of high dose daily amifostine. The control and survival rates compare favorably with previously published data.