Cancer Res Treat.  2023 Jan;55(1):189-195. 10.4143/crt.2021.1527.

A Phase II Study of Preoperative Chemoradiotherapy with Capecitabine Plus Simvastatin in Patients with Locally Advanced Rectal Cancer

• Jo H
• Kim ST
• Lee J
• Park SH
• Park JO
• Park YS
• Lim HY
• Yu JI
• Park HC
• Choi DH
• Park Y
• Cho YB
• Huh JW
• Yun SH
• Kim HC
• Lee WY
• Kang WK

• KMID: 2538004
• DOI: http://doi.org/10.4143/crt.2021.1527

Abstract

Purpose
The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC).
Materials and Methods
Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity.
Results
Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin.
Conclusion
The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity.

Keyword

Rectal neoplasms; Simvastatin; Capecitabine; Preoperative chemoradiotherapy; Pathologic complete response

Figure

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  Fig. 1 CONSORT diagram. CCRT, concurrent chemoradiotherapy; TME, total mesorectal excision.

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  Fig. 2 Kaplan-Meier survival curve of disease-free survival (DFS) (A) and overall survival (OS) (B).

Reference

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