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

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.

• Authors: Youjin Kim, 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
• Journal: Cancer research and treatment (Cancer Res Treat) Vol. 51 Issue 3 Pg. 1128-1134 (Jul 2019) ISSN: 2005-9256 [Electronic] Korea (South)
• PMID: 30477287 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Oxaloacetates
• Deoxycytidine
• Bevacizumab
• Capecitabine
• Simvastatin
• Fluorouracil

Topics

• Administration, Intravenous
• Administration, Oral
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Bevacizumab (administration & dosage, adverse effects)
• Capecitabine
• Colorectal Neoplasms (drug therapy)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Female
• Fluorouracil (administration & dosage, adverse effects, analogs & derivatives)
• Humans
• Male
• Middle Aged
• Oxaloacetates
• Prognosis
• Simvastatin (administration & dosage, adverse effects)
• Survival Analysis
• Treatment Outcome