title: A Phase II Study to Prevent Radiation-induced Rectal Injury With Lovastatin.
abstract: Physician reported symptomatic late rectal injury occurs in about 5% to 25% of patients treated with radiation therapy for prostate cancer, depending on the treatment technique. Patients, however, report clinically meaningful declines in bowel/rectal function regardless of the technique used. Lovastatin has been shown to protect mice from late radiation injury. This study was designed to determine if lovastatin might reduce the incidence of late rectal injury in patients receiving radiation therapy for prostate cancer.
  
  
  
  Patients with adenocarcinoma of the prostate receiving radiotherapy with curative intent were eligible. A portion of the rectum had to receive at least 60 Gy. Gastrointestinal functioning was assessed using both physician-reported and patient-reported instruments at baseline and at prescribed intervals during and after treatment. Lovastatin (20 to 80 mg/d) was started on day 1 of radiation and continued for 12 months. Patients were followed for an additional 12 months. The primary endpoint was physician-reported rectal toxicity ≥grade 2 during the first 2 years after treatment.
  
  
  
  A total of 20/53 (38%) patients developed grade 2 or higher toxicity during the 2-year follow-up period. Seventeen patients had 1 or more unresolved gastrointestinal symptom at the end of 2 years, 3 (6%) of which were grade 2 and none were of higher grade.
  
  
  
  The primary endpoint of the study was not met. Lovastatin, as administered in this trial, did not reduce the incidence of grade 2 or higher rectal toxicity compared with historical controls.
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Anscher
authors.affiliation: Departments of Radiation Oncology.|Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Chang
authors.affiliation: Departments of Radiation Oncology.|Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA.
authors.forename: Drew
authors.initials: D
authors.lastname: Moghanaki
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Rosu
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Ross B
authors.initials: RB
authors.lastname: Mikkelsen
authors.affiliation: The Massey Cancer Center, Virginia Commonwealth University.
authors.forename: Diane
authors.initials: D
authors.lastname: Holdford
authors.affiliation: The Massey Cancer Center, Virginia Commonwealth University.
authors.forename: Vicki
authors.initials: V
authors.lastname: Skinner
authors.affiliation: Surgery.
authors.forename: Baruch M
authors.initials: BM
authors.lastname: Grob
authors.affiliation: Medicine.
authors.forename: Arun
authors.initials: A
authors.lastname: Sanyal
authors.affiliation: Biostatistics.
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.affiliation: Biostatistics.
authors.forename: Nitai D
authors.initials: ND
authors.lastname: Mukhopadhyay
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D011835:Radiation Protection; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012007:Rectum / Q000528:radiation effects*
chemical_list: D000924:Anticholesteremic Agents; D008148:Lovastatin