Radical hypofractionated accelerated radiotherapy with cytoprotection for invasive bladder cancer.
OBJECTIVE
To report a series of patients with bladder cancer treated with hypofractionated accelerated radiotherapy with amifostine cytoprotection, with or without concurrent liposomal doxorubicin. Radiochemotherapy has been shown to be an effective alternative to cystectomy.


METHODS
A total of 38 patients with invasive bladder cancer were treated with 15 consecutive fractions of 3.4 Gy (2.7 Gy to the pelvis and a 0.7-Gy concomitant boost to the bladder; total biologic dose 66 to 72 Gy in 19 days). An individualized amifostine dose of up to 1000 mg was given subcutaneously before each radiotherapy fraction. Nineteen patients received concomitant liposomal doxorubicin (25 mg/m2 every 2 weeks for six cycles).


RESULTS
Of the 38 patients, 33 tolerated a daily amifostine dose of 750 to 1000 mg well. For these patients, the acute radiation toxicity in the bladder and rectum was minimal. Liposomal doxorubicin did not increase radiation sequela and had no systemic side effects. At a median follow-up of 22 months, severe late sequelae were infrequent (5.5% dysuria grade 2, 7.8% frequency grade 1, and 2.8% incontinence grade 2). Cystoscopy confirmed significant bladder shrinkage in 8% of patients. Intermittent rectal urgency was noted in only 5.5% of patients. A complete response was obtained in 32 (84.2%) of 38 patients. Despite the 10% greater complete response rate noted in patients receiving chemotherapy, the difference did not reach statistical significance. The 2-year local relapse-free survival rate was 80%.


CONCLUSIONS
Hypofractionated accelerated radiotherapy with amifostine cytoprotection with or without concomitant liposomal doxorubicin provided high control rates of bladder cancer with low toxicity, and also had the advantage of reducing by 4 weeks the overall treatment time compared with standard radiotherapy.
Koukourakis
Michael I
MI
Department of Radiotherapy and Oncology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece. targ@her.forthnet.gr
Tsolos
Christos
C
Touloupidis
Stavros
S
D000368:Aged; D000369:Aged, 80 and over; D004999:Amifostine / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001707:Biopsy, Needle; D002295:Carcinoma, Transitional Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D019610:Cytoprotection; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D011882:Radiotherapy, High-Energy / Q000379:methods*; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*
D004317:Doxorubicin; D004999:Amifostine