Cancer Res Treat.  2019 Jul;51(3):1128-1134. 10.4143/crt.2018.379.

A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients

• Kim Y
• Kim TW
• Han SW
• Ahn JB
• Kim ST
• Lee J
• Park JO
• Park YS
• Lim HY
• Kang WK

• KMID: 2454304
• DOI: http://doi.org/10.4143/crt.2018.379

Abstract

PURPOSE
Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC).
MATERIALS AND METHODS
Patients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m² plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m² twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity.
RESULTS
From January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation.
CONCLUSION
Based on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity.

Keyword

Colorectal neoplasms; Simvastatin; XELOX; Bevacizumab

MeSH Terms

Apoptosis
Arm*
Bevacizumab*
Capecitabine
Cell Aging
Colorectal Neoplasms*
Creatine Kinase
Disease-Free Survival
Drug Therapy*
Follow-Up Studies
Humans
Liver
Simvastatin*
Tablets
Treatment Outcome
Bevacizumab
Capecitabine
Creatine Kinase
Simvastatin
Tablets

Figure

• 

  Fig. 1. Progression-free survival (PFS) (A) and overall survival (OS) (B) with simvastatin plus XELOX and bevacizumab in metastatic colorectal cancer patients.

Reference

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