Acute symptoms, not rectally administered sucralfate, predict for late radiation proctitis: longer term follow-up of a phase III trial--Trans-Tasman Radiation Oncology Group.
OBJECTIVE
To assess the potential for sucralfate administered rectally to reduce the risk of late rectal morbidity in patients undergoing nonconformal radiotherapy (RT) for carcinoma of the prostate and to study the variables potentially contributing to late rectal morbidity and particularly to explore the relationship between acute and late toxicity.


METHODS
Eighty-six patients with localized prostate carcinoma were randomized in a double-blind, placebo-controlled study to a daily enema of 3 g of sucralfate in a 15-mL suspension or the same suspension without sucralfate. The enema began the first day of RT and was continued for 2 weeks after treatment completion. The primary end point of the study was acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) toxicity; however, the patients were followed for an additional 5 years on a 6-month basis. The evaluation included late RTOG/EORTC toxicity and a patient self-assessment questionnaire.


RESULTS
With a median follow-up of 5 years, the Kaplan-Meier probability of late Grade 2 RTOG/EORTC toxicity was 12% (95% confidence interval [CI] 2-22%) for placebo and 5% (95% CI 0-12%) for sucralfate (p = 0.26). The probability of late rectal bleeding was 59% (95% CI 45-73%) for placebo and 54% (95% CI 40-68%) for sucralfate. No statistically significant difference was found between the treatment arms for the peak incidence of any of the other patient self-assessment variables. Cox proportional hazards modeling indicated acute RTOG/EORTC toxicity of Grade 2 or greater was associated with a hazard ratio of 2.74 (95% CI 1.31-5.73) for the development of late toxicity of Grade 1 or greater. Substituting the patient self-assessment variables for acute RTOG/EORTC toxicity revealed that rectal pain of a moderate or severe grade during RT was the best predictor of the subsequent development of late toxicity, with a hazard ratio of 3.44 (95% CI 1.68-7).


CONCLUSIONS
The results of this study do not support the use of sucralfate administered rectally as a method for reducing the late toxicity of nonconformal RT for prostate cancer. There appears to be an association between the development of acute and subsequent late toxicity, although the nature of this association remains to be determined.
O'Brien
Peter C
PC
Department of Radiation Oncology, Newcastle Mater Hospital, Newcastle, NSW, Australia. mdpco@alinga.newcastle.edu.au
Franklin
C Ian
CI
Poulsen
Michael G
MG
Joseph
David J
DJ
Spry
Nigel S
NS
Denham
James W
JW
D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D016001:Confidence Intervals; D004311:Double-Blind Method; D004733:Enema; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000517:prevention & control*; D012002:Rectal Diseases / Q000209:etiology / Q000517:prevention & control*; D012007:Rectum / Q000187:drug effects / Q000528:radiation effects*; D013392:Sucralfate / Q000008:administration & dosage*
D000897:Anti-Ulcer Agents; D013392:Sucralfate