title: Evaluating the efficacy of statins and ACE-inhibitors in reducing gastrointestinal toxicity in patients receiving radiotherapy for pelvic malignancies.
abstract: BACKGROUND
  3-Hydroxy-methylglutaryl coenzyme-a reductase inhibitors (statins) improve survival following pelvic irradiation for cancer. Large studies suggest that patients with hypertension may have reduced gastrointestinal (GI) toxicity. Animal data suggest that statins and ACE inhibitors (ACEi) may protect against normal tissue injury. Their efficacy in humans has not been reported.
  
  
  OBJECTIVE
  To evaluate the impact of statins and ACEi on normal tissue toxicity during radical pelvic radiotherapy. GI symptomatology was recorded prospectively before radiotherapy, weekly during treatment and 1 year later using the inflammatory bowel disease questionnaire-bowel (IBDQ-B) subset. Cumulative acute toxicity (IBDQ-B AUC) and worst score were determined. Dose, brand and duration of statin and/or ACEi usage were obtained from General Practitioners.
  
  
  RESULTS
  Of 308 patients recruited, 237 had evaluable acute drug and toxicity data and 164 had data at 1year. Acutely, 38 patients (16%) were taking statins, 39 patients (16.5%) were taking ACEi and 18 patients (7.6%) were taking statin+ACEi. Mean changes in acute scores were 7.3 points (non-statin users), 7.3 (non-ACEi users) and 7.0 (non-statin+ACEi users) compared to 4.8 points (statin users), 5.0 points (ACEi users) and 4.9 points (statin+ACEi users). Statin use (p=0.04) and combined statin+ACEi use (p=0.008) were associated with reduced acute IBDQ-B AUC after controlling for baseline scores (ANOVA). At 1 year, users maintained higher IBDQ-B scores than non-users in all user subgroups.
  
  
  CONCLUSIONS
  Use of statin or statin+ACEi medication during radical pelvic radiotherapy significantly reduces acute gastrointestinal symptoms scores and also appears to provide longer-term sustained protection.
authors.affiliation: Department of Nutrition and Dietetics, The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Wedlake
authors.forename: Foteini
authors.initials: F
authors.lastname: Silia
authors.forename: Barbara
authors.initials: B
authors.lastname: Benton
authors.forename: Amyn
authors.initials: A
authors.lastname: Lalji
authors.forename: Karen
authors.initials: K
authors.lastname: Thomas
authors.forename: David P
authors.initials: DP
authors.lastname: Dearnaley
authors.forename: Peter
authors.initials: P
authors.lastname: Blake
authors.forename: Diana
authors.initials: D
authors.lastname: Tait
authors.forename: Vincent S
authors.initials: VS
authors.lastname: Khoo
authors.forename: H Jervoise N
authors.initials: HJ
authors.lastname: Andreyev
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005767:Gastrointestinal Diseases / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008131:London; D008297:Male; D008875:Middle Aged; D010386:Pelvic Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D011878:Radiotherapy / Q000009:adverse effects; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors