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

Young Woong Won, Hyewon Lee, Hyeon Seok Eom, Jin Seok Kim, Cheolwon Suh, Dok Hyun Yoon, Jung Yong Hong, Hye Jin Kang, Jae Hoon Lee, Won Seog Kim, Seok Jin Kim, Won Sik Lee, Myung Hee Chang, Young Rok Do, Jun Ho Yi, Inho Kim, Jong Ho Won, Kyoungha Kim, Sung Yong Oh, Jae Cheol Jo

Research output: Contribution to journalArticle

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

Original languageEnglish
Pages (from-to)255-264
Number of pages10
JournalAnnals of Hematology
Volume99
Issue number2
DOIs
StatePublished - 1 Feb 2020

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oxaliplatin
Cytarabine
Methylprednisolone
Etoposide
Hodgkin Disease
Lymphotoxin-beta
C-Reactive Protein
Mucositis
Time and Motion Studies
Anorexia
Exanthema
Combination Drug Therapy
Neutropenia
Thrombocytopenia
Nausea
Vascular Endothelial Growth Factor A
Tumor Necrosis Factor-alpha
Biomarkers
Confidence Intervals
Cytokines

Keywords

  • Cytarabine
  • Etoposide
  • Hodgkin’s lymphoma
  • Methylprednisolone
  • Oxaliplatin

Cite this

Won, Young Woong ; Lee, Hyewon ; Eom, Hyeon Seok ; Kim, Jin Seok ; Suh, Cheolwon ; Yoon, Dok Hyun ; Hong, Jung Yong ; Kang, Hye Jin ; Lee, Jae Hoon ; Kim, Won Seog ; Kim, Seok Jin ; Lee, Won Sik ; Chang, Myung Hee ; Do, Young Rok ; Yi, Jun Ho ; Kim, Inho ; Won, Jong Ho ; Kim, Kyoungha ; Oh, Sung Yong ; Jo, Jae Cheol. / A phase II study of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) for patients with refractory or relapsed Hodgkin’s lymphoma. In: Annals of Hematology. 2020 ; Vol. 99, No. 2. pp. 255-264.
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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",
keywords = "Cytarabine, Etoposide, Hodgkin’s lymphoma, Methylprednisolone, Oxaliplatin",
author = "Won, {Young Woong} and Hyewon Lee and Eom, {Hyeon Seok} and Kim, {Jin Seok} and Cheolwon Suh and Yoon, {Dok Hyun} and Hong, {Jung Yong} and Kang, {Hye Jin} and Lee, {Jae Hoon} and Kim, {Won Seog} and Kim, {Seok Jin} and Lee, {Won Sik} and Chang, {Myung Hee} and Do, {Young Rok} and Yi, {Jun Ho} and Inho Kim and Won, {Jong Ho} and Kyoungha Kim and Oh, {Sung Yong} and Jo, {Jae Cheol}",
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Won, YW, Lee, H, Eom, HS, Kim, JS, Suh, C, Yoon, DH, Hong, JY, Kang, HJ, Lee, JH, Kim, WS, Kim, SJ, Lee, WS, Chang, MH, Do, YR, Yi, JH, Kim, I, Won, JH, Kim, K, Oh, SY & Jo, JC 2020, 'A phase II study of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) for patients with refractory or relapsed Hodgkin’s lymphoma', Annals of Hematology, vol. 99, no. 2, pp. 255-264. https://doi.org/10.1007/s00277-019-03891-9

A phase II study of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) for patients with refractory or relapsed Hodgkin’s lymphoma. / Won, Young Woong; Lee, Hyewon; Eom, Hyeon Seok; Kim, Jin Seok; Suh, Cheolwon; Yoon, Dok Hyun; Hong, Jung Yong; Kang, Hye Jin; Lee, Jae Hoon; Kim, Won Seog; Kim, Seok Jin; Lee, Won Sik; Chang, Myung Hee; Do, Young Rok; Yi, Jun Ho; Kim, Inho; Won, Jong Ho; Kim, Kyoungha; Oh, Sung Yong; Jo, Jae Cheol.

In: Annals of Hematology, Vol. 99, No. 2, 01.02.2020, p. 255-264.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A phase II study of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) for patients with refractory or relapsed Hodgkin’s lymphoma

AU - Won, Young Woong

AU - Lee, Hyewon

AU - Eom, Hyeon Seok

AU - Kim, Jin Seok

AU - Suh, Cheolwon

AU - Yoon, Dok Hyun

AU - Hong, Jung Yong

AU - Kang, Hye Jin

AU - Lee, Jae Hoon

AU - Kim, Won Seog

AU - Kim, Seok Jin

AU - Lee, Won Sik

AU - Chang, Myung Hee

AU - Do, Young Rok

AU - Yi, Jun Ho

AU - Kim, Inho

AU - Won, Jong Ho

AU - Kim, Kyoungha

AU - Oh, Sung Yong

AU - Jo, Jae Cheol

PY - 2020/2/1

Y1 - 2020/2/1

N2 - 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

AB - 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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KW - Etoposide

KW - Hodgkin’s lymphoma

KW - Methylprednisolone

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