title: Daily sodium butyrate enema for the prevention of radiation proctitis in prostate cancer patients undergoing radical radiation therapy: results of a multicenter randomized placebo-controlled dose-finding phase 2 study.
abstract: OBJECTIVE
  To evaluate the efficacy of sodium butyrate enemas (NABUREN) in prostate cancer radiation therapy (RT) in reducing the incidence, severity, and duration of acute RT-induced proctitis.
  
  
  METHODS
  166 patients, randomly allocated to 1 of 4 groups (rectal sodium butyrate 1 g, 2 g, or 4 g daily or placebo), were treated with NABUREN during and 2 weeks after RT. The grade of proctitis was registered in a daily diary. The correlation between NABUREN and proctitis was investigated through χ(2) statistics. The toxicity endpoints considered were as follows: total number of days with grade ≥1 proctitis (≥G1); total number of days with grade ≥2 proctitis (≥G2); ≥G1 and ≥G2 proctitis lasting at least 3 and 5 consecutive days starting from week 4 (≥G1+3d, ≥G2+3d); damaging effects of RT on rectal mucosa as measured by endoscopy. The relationship between endpoints and pretreatment morbidities, hormonal therapy, presence of diabetes or hypertension, abdominal surgery, or hemorrhoids was investigated by univariate analysis.
  
  
  RESULTS
  The patients were randomly allocated to the 4 arms. No difference in the distribution of comorbidities among the arms was observed (P>.09). The mean ≥G1 and ≥G2 proctitis were 7.8 and 4.9 for placebo and 8.9 and 4.7 for the NABUREN group, respectively. No favorable trend in reduction of incidence, severity, and duration of ≥G1 and ≥G2 proctitis was observed with NABUREN use. In univariate analysis, ≥G1+3d toxicity was found to be related to hemorrhoids (P=.008), and a slight correlation was found between ≥G2 proctitis and hormonal therapy (P=.06). The RT effects on rectal mucosa as based on endoscopic assessment were mainly related to diabetes (P<.01). Endoscopy data at 6 week showed no significant difference between the placebo and butyrate arms. The other investigated endpoints were not correlated with any of the clinical risk factors analyzed.
  
  
  CONCLUSIONS
  There was no evidence of efficacy of NABUREN in reducing the incidence, severity, and duration of acute radiation proctitis. There was a correlation between some endpoints and clinical risk factors.
authors.affiliation: Medical Physics, San Raffaele Scientific Institute, Milan, Italy. Electronic address: maggio.angelo@gmail.com.
authors.forename: Angelo
authors.initials: A
authors.lastname: Maggio
authors.affiliation: Department of Radiotherapy, Ospedale S. Maria della Misericordia, Udine, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Magli
authors.affiliation: Prostate Cancer Programme, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rancati
authors.affiliation: Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Fiorino
authors.affiliation: Division of Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Valvo
authors.affiliation: Department of Radiotherapy, Ospedale Santa Chiara, Trento, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fellin
authors.affiliation: University of Turin, Department of Oncology, Torino, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Ricardi
authors.affiliation: Radiotherapy Unit, AO Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Fernando
authors.initials: F
authors.lastname: Munoz
authors.affiliation: Ospedale S. Anna, Como, Italy.
authors.forename: Dorian
authors.initials: D
authors.lastname: Cosentino
authors.affiliation: Ospedale S. Anna, Como, Italy.
authors.forename: Luigi Franco
authors.initials: LF
authors.lastname: Cazzaniga
authors.affiliation: Prostate Cancer Programme, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Division of Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Valdagni
authors.affiliation: Department of Radiotherapy, Ospedale di Circolo, Varese, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Vavassori
mesh_terms: D000208:Acute Disease; D000285:Administration, Rectal; D000704:Analysis of Variance; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects; D020148:Butyric Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D048909:Diabetes Complications / Q000473:pathology; D004311:Double-Blind Method; D004733:Enema / Q000379:methods*; D006484:Hemorrhoids / Q000150:complications; D006801:Humans; D007413:Intestinal Mucosa / Q000528:radiation effects; D008297:Male; D011349:Proctitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000473:pathology / Q000517:prevention & control*; D012007:Rectum / Q000528:radiation effects*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D020148:Butyric Acid