Evaluating the efficacy of statins and ACE-inhibitors in reducing gastrointestinal toxicity in patients receiving radiotherapy for pelvic malignancies

Eur J Cancer. 2012 Sep;48(14):2117-24. doi: 10.1016/j.ejca.2011.12.034. Epub 2012 Mar 3.

Abstract

Introduction: 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.

Aims/methods: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Female
  • Gastrointestinal Diseases / diagnosis
  • Gastrointestinal Diseases / etiology
  • Gastrointestinal Diseases / mortality
  • Gastrointestinal Diseases / prevention & control*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • London
  • Male
  • Middle Aged
  • Pelvic Neoplasms / mortality
  • Pelvic Neoplasms / radiotherapy*
  • Radiation Dosage
  • Radiation Injuries / etiology
  • Radiation Injuries / mortality
  • Radiation Injuries / prevention & control*
  • Radiotherapy / adverse effects
  • Retrospective Studies
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Outcome

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors