SPAR: A randomised, placebo-controlled phase II trial of Simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer

Rectal cancer commonly presents with locally-advanced disease, with poorer local control and/or distant metastasis rates seen with higher tumour stage, threatened or involved mesorectal fascia, locoregional nodal involvement and extramural venous invasion. Tumour response to pCRT correlates with cancer outcomes, but 60% of high-risk patients have poor tumour responses and double the risk of relapse compared to good responders.

Retrospective studies have shown improved outcomes in rectal cancer patients who take statins during radiotherapy, including overall survival, pathological tumour response to pCRT and acute and late toxicities of pelvic radiation. Major or complete tumour regression following pCRT, assessed in vivo using MRI-based tumour regression grading (mrTRG) several weeks after pCRT, or using pathological tumour regression grading (pathTRG) after resection, has strong prognostic significance.

SPAR aims to evaluate the effect of simvastatin (SIM) on the efficacy and toxicity of preoperative chemoradiation (pCRT) in rectal cancer patients, and on systemic and local inflammatory responses.