A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients
- Author:
Youjin KIM
1
;
Tae Won KIM
;
Sae Won HAN
;
Joong Bae AHN
;
Seung Tae KIM
;
Jeeyun LEE
;
Joon Oh PARK
;
Young Suk PARK
;
Ho Yeong LIM
;
Won Ki KANG
Author Information
- Publication Type:Original Article
- Keywords: Colorectal neoplasms; Simvastatin; XELOX; Bevacizumab
- MeSH: Apoptosis; Arm; Bevacizumab; Capecitabine; Cell Aging; Colorectal Neoplasms; Creatine Kinase; Disease-Free Survival; Drug Therapy; Follow-Up Studies; Humans; Liver; Simvastatin; Tablets; Treatment Outcome
- From:Cancer Research and Treatment 2019;51(3):1128-1134
- CountryRepublic of Korea
- Language:English
- 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.
