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A phase I study of everolimus and CHOP in newly diagnosed peripheral T-cell lymphomas

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Summary

Background We performed a phase I study to determine the dose and safety of everolimus as a combination chemotherapy in peripheral T-cell lymphoma (PTCL). Methods Four dose levels (2.5 to 10 mg) of everolimus from days 1 to 14 with CHOP (750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, and 1.4 mg/m2 (maximum 2 mg) vincristine on day 1, and 100 mg/day prednisone on days 1 to 5) every 21 days were planned. Results Fifteen patients newly diagnosed with stage III/IV PTCL were enrolled. One of 6 patients at dose level 2 (5 mg everolimus) had grade 3 hepatotoxicity and 3 of 6 patients at level 3 (7.5 mg everolimus) had grade 4 hematologic toxicities (two grade 4 thrombocytopenia and one grade 4 neutropenia with fever lasting more than 3 days). The recommended dose of everolimus for combination was 5 mg. There were no differences in steady state trough concentrations of everolimus between cycles 1 and 2 for all three dose levels. All evaluable patients achieved response (8 complete and 6 partial). Conclusions Everolimus (5 mg) can be safely combined with CHOP leading to a feasible and effective regimen for PTCL. The subsequent phase II is now in progress.

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Disclosure of conflicts of interest

Won Seog Kim received the research funding in Novartis, and everolimus was donated by Novartis.

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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, South Korea

    Seok Jin Kim & Won Seog Kim

  2. Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, South Korea

    Hye Jin Kang

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

    Jin Seok Kim

  4. Hematology-Oncology Clinic, National Cancer Center, Goyang-city, South Korea

    Hyeon-Seok Eom

  5. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Jooryung Huh

  6. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Young Hyeh Ko

  7. Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, South Korea

    Jongtae Lee & Dong-Seok Yim

  8. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan, University School of Medicine, Seoul, South Korea

    Soo-Youn Lee

  9. Department of Pathology, Center for Prostate Cancer and Center for Specific Organs Cancer Research Institute and Hospital, National Cancer Center, Goyang-city, South Korea

    Weon Seo Park

  10. Department of Pathology, Severance Hospital Yonsei University Health System, Seoul, South Korea

    Woo Ick Yang

  11. Department of Pathology, Korea Cancer Center Hospital, Seoul, South Korea

    Seung-Sook Lee

  12. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Ulsan, South Korea

    Cheolwon Suh

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  1. Seok Jin Kim
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  12. Seung-Sook Lee
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  14. Won Seog Kim
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Correspondence to Won Seog Kim.

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Kim, S.J., Kang, H.J., Kim, J.S. et al. A phase I study of everolimus and CHOP in newly diagnosed peripheral T-cell lymphomas. Invest New Drugs 31, 1514–1521 (2013). https://doi.org/10.1007/s10637-013-0015-z

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  • DOI: https://doi.org/10.1007/s10637-013-0015-z

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