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Simvastatin plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line chemotherapy in metastatic colorectal patients: a multicenter phase II study

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Abstract

Background

Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, anti-angiogenesis, and apoptosis. This phase II trial evaluated the efficacy and toxicity profile of conventional FOLFIRI chemotherapy plus simvastatin in metastatic colorectal cancer patients.

Methods

Patients received irinotecan 180 mg/m2 as a 90-min infusion followed by leucovorin 200 mg/m2 in a 2-h infusion, and then 5-FU 400 mg/m2 bolus injection followed by 2,400 mg/m2 as a 46-h continuous infusion. Treatment cycles were repeated every 2 weeks until documented disease progression, unacceptable toxicity, or patient’s refusal. Simvastatin 40 mg tablet was given once daily per oral everyday during the period of chemotherapy without a rest.

Results

From October 2005 to June 2006, 49 patients were enrolled. The overall response rate (ORR) was 46.9% (95% CI, 31.0–58.8) by intent-to-treat analysis and 45.8% (95% CI, 33.3–62.8) by per-protocol analysis. There were one complete response (CR) and 22 partial responses (PRs). Both CR and PRs were confirmed at least 4 weeks later. The disease-control rate was 83.7% (95% CI, 73.4–94.0). The median follow-up duration was 25.6 months (range, 20.9–28.8 months). The median survival of all patients was 21.8 months (95% CI, 14.4, 29.2). The median TTP was 9.9 months (95% CI, 6.4, 13.3). No patients experienced additional adverse effect that was definitely caused by simvastatin drug therapy in this trial.

Conclusion

The combination of simvastatin plus FOLFIRI was a feasible regimen with promising antitumor activity.

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Acknowledgment

We acknowledge the CJ Corp. who kindly donated simvastatin for the study. This study was supported by Grant No. 0412-CR01-0704-0001 of the Korea Health 21 R & D Project, Ministry of Health & Welfare, Republic of Korea.

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong Kangnam-Gu, Seoul, 135-710, Korea

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

  2. Center for Colorectal Cancer, National Cancer Center, Research Institute and Hospital, Goyang, Korea

    Kyung Hae Jung & Yong Sang Hong

  3. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

    Joong Bae Ahn & Sang Jun Shin

  4. Department of Internal Medicine, Seoul National University College of Medicine, Chongro-gu, Seoul, Korea

    Seock-Ah Im & Do Youn Oh

  5. Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea

    Dong Bok Shin

  6. Division of Oncology, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Kyung Hae Jung & Tae Won Kim

  7. Division of Hematology-Oncology, Soon Chun Hyang University Hospital, Seoul, Korea

    Namsu Lee

  8. Department of Internal Medicine, St Mary’s Hospital, The Catholic University of Korea, Seoul, Korea

    Jae Ho Byun

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  1. Jeeyun Lee
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Correspondence to Won Ki Kang.

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Lee, J., Jung, K.H., Park, Y.S. et al. Simvastatin plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line chemotherapy in metastatic colorectal patients: a multicenter phase II study. Cancer Chemother Pharmacol 64, 657–663 (2009). https://doi.org/10.1007/s00280-008-0913-5

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