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Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients

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Abstract

Background

Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis. A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine. The present randomized, double-blinded, phase II trial compared the efficacy and safety of gemcitabine plus simvastatin (GS) with those of gemcitabine plus placebo (GP) in patients with locally advanced and metastatic pancreatic cancer.

Methods

Patients were randomly assigned to receive a 3-week regimen with GS (gemcitabine 1,000 mg/m2 on days 1, 8, and 15 plus simvastatin 40 mg once daily) or GP (gemcitabine 1,000 mg/m2 on days 1, 8, and 15 plus placebo). The primary end point was time to progression (TTP).

Results

Between December 2008 and April 2012, 114 patients were enrolled. The median TTP was not significantly different between the two arms, being 2.4 months (95 % CI 0.7–4.1 months) and 3.6 months (95 % CI 3.1–4.1 months) in the GS and GP arms, respectively (P = 0.903). The overall disease control rate was 39.7 % (95 % CI 12.2–33.8 %) and 57.1 % (95 % CI 19.8–44.2 %) in the GS and GP arms, respectively (P = 0.09). The 1-year expected survival rates were similar (27.7 and 31.7 % in the GS and GP arms, respectively; P = 0.654). Occurrence of grade 3 or 4 adverse events was similar in both arms, and no patients had rhabdomyolysis.

Conclusions

Adding low-dose simvastatin to gemcitabine in advanced pancreatic cancer does not provide clinical benefit, although it also does not result in increased toxicity. Given the emerging role of statins in overcoming resistance to anti-EGFR treatment, further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents, such as erlotinib or cetuximab, plus gemcitabine for treating advanced pancreatic cancer.

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Acknowledgments

This work was supported by Grants from the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102166).

Conflict of interest

None.

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul, 135-710, Korea

    Jung Yong Hong, Jeeyun Lee, Joon Oh Park, Se Hoon Park, Ho Yeong Lim, Won Ki Kang & Young Suk Park

  2. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Seong Ho Choi & Jin Seok Heo

  3. Division of Hematology-Oncology, Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, Korea

    Eun Mi Nam

  4. Division of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea

    Sang-Cheol Lee

  5. Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea

    Seo-Young Song

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  1. Jung Yong Hong
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Corresponding author

Correspondence to Young Suk Park.

Additional information

Jung Yong Hong and Eun Mi Nam have contributed equally to the work presented here.

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Hong, J.Y., Nam, E.M., Lee, J. et al. Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients. Cancer Chemother Pharmacol 73, 125–130 (2014). https://doi.org/10.1007/s00280-013-2328-1

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