Results of a phase II study of vorinostat in combination with intravenous fludarabine, mitoxantrone, and dexamethasone in patients with relapsed or refractory mantle cell lymphoma: An interim analysis

Dong Yeop Shin, Seok Jin Kim, Dok Hyun Yoon, Yong Park, Jee Hyun Kong, Jeong A. Kim, Byung Su Kim, Hyo Jung Kim, Jong Ho Won, Sung Kyu Park, Won Seog Kim

Research output: Contribution to journalArticle

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Abstract

Purpose: Mantle cell lymphoma (MCL) is a disease that frequently relapses and primarily affects elderly people. We performed an open-label, multi-center, phase II study to investigate the effect and quality of life (QoL) of treatment with vorinostat in combination with fludarabine, mitoxantrone and dexamethasone (V-FND) for relapsed or refractory MCL. Methods: The treatment schedule was composed of four cycles of induction treatment with V-FND and subsequent consolidation therapy involving autologous hematopoietic stem cell transplantation or six cycles of vorinostat maintenance. QoL was assessed using EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) every 2 cycles. Results: Data from a total of 20 patients were collected for an interim analysis. The median age was 67 years (range 49-75), and 14 or the patients (70 %) were male. The full course of V-FND induction treatment was completed in 11 patients, but only three completed all six cycles of maintenance therapy. Response to V-FND was not available in two patients. Among the other 18 patients, the objective response rate was 77.8 % (complete response in five patients + partial response in nine patients). Median progression-free survival was 9.3 months [95 % confidence interval (CI) 4.0-12.3]. Fifteen patients (75 %) experienced grade 3/4 toxicities. Analysis of QoL demonstrated significant deterioration of social functioning (p = 0.01), and significant aggravation of fatigue and nausea/vomiting (p = 0.04 and 0.01, respectively) after two cycles of V-FND induction. Conclusions: V-FND is effective in patients with relapsed or refractory MCL. However, significant toxicities were hurdles to sustained V-FND therapy.

Original languageEnglish
Pages (from-to)865-873
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume77
Issue number4
DOIs
Publication statusPublished - 2016 Apr 1

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Mantle-Cell Lymphoma
Mitoxantrone
Refractory materials
Dexamethasone
Toxicity
Stem cells
Consolidation
Deterioration
Labels
Fatigue of materials
Quality of Life
Therapeutics
fludarabine
vorinostat
Hematopoietic Stem Cell Transplantation
Nausea
Disease-Free Survival
Vomiting
Fatigue
Appointments and Schedules

Keywords

  • Mantle cell lymphoma
  • Phase II
  • Relapsed lymphoma
  • Vorinostat

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Results of a phase II study of vorinostat in combination with intravenous fludarabine, mitoxantrone, and dexamethasone in patients with relapsed or refractory mantle cell lymphoma : An interim analysis. / Shin, Dong Yeop; Kim, Seok Jin; Yoon, Dok Hyun; Park, Yong; Kong, Jee Hyun; Kim, Jeong A.; Kim, Byung Su; Kim, Hyo Jung; Won, Jong Ho; Park, Sung Kyu; Kim, Won Seog.

In: Cancer Chemotherapy and Pharmacology, Vol. 77, No. 4, 01.04.2016, p. 865-873.

Research output: Contribution to journalArticle

Shin, Dong Yeop ; Kim, Seok Jin ; Yoon, Dok Hyun ; Park, Yong ; Kong, Jee Hyun ; Kim, Jeong A. ; Kim, Byung Su ; Kim, Hyo Jung ; Won, Jong Ho ; Park, Sung Kyu ; Kim, Won Seog. / Results of a phase II study of vorinostat in combination with intravenous fludarabine, mitoxantrone, and dexamethasone in patients with relapsed or refractory mantle cell lymphoma : An interim analysis. In: Cancer Chemotherapy and Pharmacology. 2016 ; Vol. 77, No. 4. pp. 865-873.
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abstract = "Purpose: Mantle cell lymphoma (MCL) is a disease that frequently relapses and primarily affects elderly people. We performed an open-label, multi-center, phase II study to investigate the effect and quality of life (QoL) of treatment with vorinostat in combination with fludarabine, mitoxantrone and dexamethasone (V-FND) for relapsed or refractory MCL. Methods: The treatment schedule was composed of four cycles of induction treatment with V-FND and subsequent consolidation therapy involving autologous hematopoietic stem cell transplantation or six cycles of vorinostat maintenance. QoL was assessed using EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) every 2 cycles. Results: Data from a total of 20 patients were collected for an interim analysis. The median age was 67 years (range 49-75), and 14 or the patients (70 {\%}) were male. The full course of V-FND induction treatment was completed in 11 patients, but only three completed all six cycles of maintenance therapy. Response to V-FND was not available in two patients. Among the other 18 patients, the objective response rate was 77.8 {\%} (complete response in five patients + partial response in nine patients). Median progression-free survival was 9.3 months [95 {\%} confidence interval (CI) 4.0-12.3]. Fifteen patients (75 {\%}) experienced grade 3/4 toxicities. Analysis of QoL demonstrated significant deterioration of social functioning (p = 0.01), and significant aggravation of fatigue and nausea/vomiting (p = 0.04 and 0.01, respectively) after two cycles of V-FND induction. Conclusions: V-FND is effective in patients with relapsed or refractory MCL. However, significant toxicities were hurdles to sustained V-FND therapy.",
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T1 - Results of a phase II study of vorinostat in combination with intravenous fludarabine, mitoxantrone, and dexamethasone in patients with relapsed or refractory mantle cell lymphoma

T2 - An interim analysis

AU - Shin, Dong Yeop

AU - Kim, Seok Jin

AU - Yoon, Dok Hyun

AU - Park, Yong

AU - Kong, Jee Hyun

AU - Kim, Jeong A.

AU - Kim, Byung Su

AU - Kim, Hyo Jung

AU - Won, Jong Ho

AU - Park, Sung Kyu

AU - Kim, Won Seog

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Purpose: Mantle cell lymphoma (MCL) is a disease that frequently relapses and primarily affects elderly people. We performed an open-label, multi-center, phase II study to investigate the effect and quality of life (QoL) of treatment with vorinostat in combination with fludarabine, mitoxantrone and dexamethasone (V-FND) for relapsed or refractory MCL. Methods: The treatment schedule was composed of four cycles of induction treatment with V-FND and subsequent consolidation therapy involving autologous hematopoietic stem cell transplantation or six cycles of vorinostat maintenance. QoL was assessed using EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) every 2 cycles. Results: Data from a total of 20 patients were collected for an interim analysis. The median age was 67 years (range 49-75), and 14 or the patients (70 %) were male. The full course of V-FND induction treatment was completed in 11 patients, but only three completed all six cycles of maintenance therapy. Response to V-FND was not available in two patients. Among the other 18 patients, the objective response rate was 77.8 % (complete response in five patients + partial response in nine patients). Median progression-free survival was 9.3 months [95 % confidence interval (CI) 4.0-12.3]. Fifteen patients (75 %) experienced grade 3/4 toxicities. Analysis of QoL demonstrated significant deterioration of social functioning (p = 0.01), and significant aggravation of fatigue and nausea/vomiting (p = 0.04 and 0.01, respectively) after two cycles of V-FND induction. Conclusions: V-FND is effective in patients with relapsed or refractory MCL. However, significant toxicities were hurdles to sustained V-FND therapy.

AB - Purpose: Mantle cell lymphoma (MCL) is a disease that frequently relapses and primarily affects elderly people. We performed an open-label, multi-center, phase II study to investigate the effect and quality of life (QoL) of treatment with vorinostat in combination with fludarabine, mitoxantrone and dexamethasone (V-FND) for relapsed or refractory MCL. Methods: The treatment schedule was composed of four cycles of induction treatment with V-FND and subsequent consolidation therapy involving autologous hematopoietic stem cell transplantation or six cycles of vorinostat maintenance. QoL was assessed using EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) every 2 cycles. Results: Data from a total of 20 patients were collected for an interim analysis. The median age was 67 years (range 49-75), and 14 or the patients (70 %) were male. The full course of V-FND induction treatment was completed in 11 patients, but only three completed all six cycles of maintenance therapy. Response to V-FND was not available in two patients. Among the other 18 patients, the objective response rate was 77.8 % (complete response in five patients + partial response in nine patients). Median progression-free survival was 9.3 months [95 % confidence interval (CI) 4.0-12.3]. Fifteen patients (75 %) experienced grade 3/4 toxicities. Analysis of QoL demonstrated significant deterioration of social functioning (p = 0.01), and significant aggravation of fatigue and nausea/vomiting (p = 0.04 and 0.01, respectively) after two cycles of V-FND induction. Conclusions: V-FND is effective in patients with relapsed or refractory MCL. However, significant toxicities were hurdles to sustained V-FND therapy.

KW - Mantle cell lymphoma

KW - Phase II

KW - Relapsed lymphoma

KW - Vorinostat

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