Sucralfate versus mesalazine versus hydrocortisone in the prevention of acute radiation proctitis during conformal radiotherapy for prostate carcinoma. A randomized study.
OBJECTIVE
To assess whether the topical use of steroids or 5-aminosalicylic acid (5-ASA) is superior to sucralfate in preventing acute rectal toxicity during three-dimensional conformal radiotherapy (3DCRT) to 76 Gy.


METHODS
Patients undergoing 3DCRT for prostate carcinoma at our institution were offered to be randomized to sucralfate 3 g in 15 ml suspension enema (Antepsin, mesalazine 4 g gel enema (Enterasyn, or hydrocortisone 100 mg foam enema (Colifoam. Randomization was blind to the treating physician but not to the patient. Sucralfate was chosen as control arm. Topical treatment had to be performed once daily, starting on day 1 of 3DCRT. Acute rectal toxicity was scored weekly according to RTOG criteria. Time to occurrence of grade 2+ acute rectal toxicity was taken as endpoint.


RESULTS
The trial was opened in August 1999, and after the first 24 patients had been treated, arm 2 was discontinued because of eight patients receiving mesalazine, seven actually developed acute rectal toxicity (five patients grade 3 and two patients grade 2). Until May 2001, 134 consecutive patients were randomly assigned to sucralfate (63 patients), mesalazine (eight patients) or hydrocortisone (63 patients). The cumulative incidence of acute rectal toxicity at the end of treatment by arm is 61.9 +/- 6.1%, 87.5 +/- 11.7%, and 52.4 +/- 6.2% for arms 1, 2, and 3, respectively. The difference between the mesalazine group and the sucralfate group is highly significant (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.1-5.7; p = 0.03). At both uni- and multivariate analysis taking into account several patients and treatment covariates, the difference between hydrocortisone and sucralfate is not significant (HR 0.7, 95% CI 0.5-1.2; p = 0.2).


CONCLUSIONS
Topical mesalazine is contraindicated during radiotherapy. Hydrocortisone enema is not superior to sucralfate in preventing acute rectal toxicity.
Sanguineti
Giuseppe
G
Department of Radiation Oncology, National Institute for Cancer Research, Genova, Italy. gisangui@utmb.edu
Franzone
Paola
P
Marcenaro
Michela
M
Foppiano
Franca
F
Vitale
Vito
V
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000075202:Contraindications; D003627:Data Interpretation, Statistical; D019583:Dose Fractionation, Radiation; D004733:Enema; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009367:Neoplasm Staging; D011349:Proctitis / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012007:Rectum / Q000528:radiation effects*; D013392:Sucralfate / Q000008:administration & dosage* / Q000009:adverse effects
D011837:Radiation-Protective Agents; D019804:Mesalamine; D013392:Sucralfate; D006854:Hydrocortisone