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A phase II study of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) for patients with refractory or relapsed Hodgkin’s lymphoma

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Abstract

We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin’s lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m2 on day 5, and i.v. oxaliplatin 130 mg/m2 on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1–46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156

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Acknowledgments

We thank Professor Sun-Young Kim (M.P.H, Ph.D, Biostatistics, Environmental Statistics and Epidemiology, National Cancer Center, South Korea) for statistical support and Dr. JongHeon Jung (M.D., Center for Hematologic Malignancy, National Cancer Center, South Korea) for the valuable review of the manuscript.

Funding

This study was supported by the Grants of the National Cancer Center, Goyang, Korea (NCC 1410210). The role of the funding was the design of the study and collection, analysis, and interpretation of data and in writing. In this study, oxaliplatin was provided by Boryung Pharmaceutical (South Korea).

Author information

Author notes

  1. Young-Woong Won and Hyewon Lee contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Seoul, South Korea

    Young-Woong Won

  2. Hematology-Oncology Clinic, Research Institute and Hospital, National Cancer Center, Goyang, South Korea

    Hyewon Lee & Hyeon-Seok Eom

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

    Hyewon Lee & ** Seok Kim

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

    Cheolwon Suh, Dok Hyun Yoon & Jung Yong Hong

  5. Division of Hematology and Medical Oncology, Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea

    Hye ** Kang

  6. Division of Hematology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea

    Jae Hoon Lee

  7. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea

    Won Seog Kim & Seok ** Kim

  8. Division of Hematology-Oncology, Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, South Korea

    Won-Sik Lee

  9. Division of Oncology-Hematology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, South Korea

    Myung Hee Chang

  10. Department of Hematology-Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, South Korea

    Young Rok Do

  11. Division of Hematology/Oncology, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea

    Jun Ho Yi

  12. Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea

    Inho Kim

  13. Division of Hematology-Oncology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University, Seoul, South Korea

    Jong-Ho Won & Kyoungha Kim

  14. Department of Internal Medicine, Dong-A University Medical Center, Dong-A University, Busan, South Korea

    Sung Yong Oh

  15. Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea

    Jae-Cheol Jo

Authors
  1. Young-Woong Won
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  20. Jae-Cheol Jo
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Contributions

Conception and design: Y Won, H Lee, H Eom, K Kim. Provision of study materials and patients: H Lee, H Eom, JS Kim, C Suh, DH Yoon, JY Hong, HJ Kang, JH Lee, WS Kim, SJ Kim, W Lee, MH Chang, YR Do, JH Yi, I Kim, J Won, K Kim, SY Oh, J Jo. Collection and assembly of data: Y Won, H Lee, H Eom. Data analysis and interpretation: Y Won, H Lee, H Eom. Manuscript writing: Y Won, H Lee, H Eom. Final approval of manuscript: All authors.

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Correspondence to Hyeon-Seok Eom.

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The authors declare that they have no competing interests.

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All patients provided written informed consent before enrollment and the study was approved by our Institutional Review Board.

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Won, YW., Lee, H., Eom, HS. et al. A phase II study of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) for patients with refractory or relapsed Hodgkin’s lymphoma. Ann Hematol 99, 255–264 (2020). https://doi.org/10.1007/s00277-019-03891-9

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