Feasibility and tolerability of trofosfamide and etoposide in progressive glioblastoma

Teresa Schmidt; Sarina Agkatsev; Jonas Feldheim; Christoph Oster; Tobias Blau; Ulrich Sure; Kathy Keyvani; Christoph Kleinschnitz; Martin Stuschke; Ken Herrmann; Cornelius Deuschl; Björn Scheffler; Sied Kebir; Martin Glas; Lazaros Lazaridis

doi:10.1093/noajnl/vdad090

Feasibility and tolerability of trofosfamide and etoposide in progressive glioblastoma

Teresa Schmidt, Sarina Agkatsev, Jonas Feldheim, Christoph Oster, Tobias Blau, Ulrich Sure, Kathy Keyvani, Christoph Kleinschnitz, Martin Stuschke, Ken Herrmann, Cornelius Deuschl, Björn Scheffler, Sied Kebir, Martin Glas, Lazaros Lazaridis

Research output: Contribution to journal › Original Article › peer-review

Abstract

BACKGROUND: Standard of care treatment options at glioblastoma relapse are still not well defined. Few studies indicate that the combination of trofosfamide plus etoposide may be feasible in pediatric glioblastoma patients. In this retrospective analysis, we determined tolerability and feasibility of combined trofosfamide plus etoposide treatment at disease recurrence of adult glioblastoma patients.

METHODS: We collected clinicopathological data from adult progressive glioblastoma patients treated with the combination of trofosfamide and etoposide for more than four weeks (one course). A cohort of patients receiving empiric treatment at the investigators' discretion balanced for tumor entity and canonical prognostic factors served as control.

RESULTS: A total of n = 22 progressive glioblastoma patients were eligible for this analysis. Median progression-free survival (3.1 vs 2.3 months, HR: 1.961, 95% CI: 0.9724-3.9560, P = .0274) and median overall survival (9.0 vs 5.7 months, HR: 4.687, 95% CI: 2.034-10.800, P = .0003) were significantly prolonged compared to the control cohort (n = 17). In a multivariable Cox regression analysis, treatment with trofosfamide plus etoposide emerged as a significant prognostic marker regarding progression-free and overall survival. We observed high-grade adverse events in n = 16/22 (73%) patients with hematotoxicity comprising the majority of adverse events (n = 15/16, 94%). Lymphopenia was by far the most commonly observed hematotoxic adverse event (n = 11/15, 73%).

CONCLUSIONS: This study provides first indication that the combination of trofosfamide plus etoposide is safe in adult glioblastoma patients. The observed survival outcomes might suggest potential beneficial effects. Our data provide a reasonable rationale for follow-up of a larger cohort in a prospective trial.

Original language	English
Pages (from-to)	vdad090
Journal	NEURO-ONCOLOGY ADVANCES
Volume	5
Issue number	1
DOIs	https://doi.org/10.1093/noajnl/vdad090
Publication status	Published - 2023
Externally published	Yes

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10.1093/noajnl/vdad090

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Schmidt, T., Agkatsev, S., Feldheim, J., Oster, C., Blau, T., Sure, U., Keyvani, K., Kleinschnitz, C., Stuschke, M., Herrmann, K., Deuschl, C., Scheffler, B., Kebir, S., Glas, M., & Lazaridis, L. (2023). Feasibility and tolerability of trofosfamide and etoposide in progressive glioblastoma. NEURO-ONCOLOGY ADVANCES, 5(1), vdad090. https://doi.org/10.1093/noajnl/vdad090

@article{ff00ff8946d04a65b36282f1bbfcaab3,

title = "Feasibility and tolerability of trofosfamide and etoposide in progressive glioblastoma",

abstract = "BACKGROUND: Standard of care treatment options at glioblastoma relapse are still not well defined. Few studies indicate that the combination of trofosfamide plus etoposide may be feasible in pediatric glioblastoma patients. In this retrospective analysis, we determined tolerability and feasibility of combined trofosfamide plus etoposide treatment at disease recurrence of adult glioblastoma patients.METHODS: We collected clinicopathological data from adult progressive glioblastoma patients treated with the combination of trofosfamide and etoposide for more than four weeks (one course). A cohort of patients receiving empiric treatment at the investigators' discretion balanced for tumor entity and canonical prognostic factors served as control.RESULTS: A total of n = 22 progressive glioblastoma patients were eligible for this analysis. Median progression-free survival (3.1 vs 2.3 months, HR: 1.961, 95% CI: 0.9724-3.9560, P = .0274) and median overall survival (9.0 vs 5.7 months, HR: 4.687, 95% CI: 2.034-10.800, P = .0003) were significantly prolonged compared to the control cohort (n = 17). In a multivariable Cox regression analysis, treatment with trofosfamide plus etoposide emerged as a significant prognostic marker regarding progression-free and overall survival. We observed high-grade adverse events in n = 16/22 (73%) patients with hematotoxicity comprising the majority of adverse events (n = 15/16, 94%). Lymphopenia was by far the most commonly observed hematotoxic adverse event (n = 11/15, 73%).CONCLUSIONS: This study provides first indication that the combination of trofosfamide plus etoposide is safe in adult glioblastoma patients. The observed survival outcomes might suggest potential beneficial effects. Our data provide a reasonable rationale for follow-up of a larger cohort in a prospective trial.",

author = "Teresa Schmidt and Sarina Agkatsev and Jonas Feldheim and Christoph Oster and Tobias Blau and Ulrich Sure and Kathy Keyvani and Christoph Kleinschnitz and Martin Stuschke and Ken Herrmann and Cornelius Deuschl and Bj{\"o}rn Scheffler and Sied Kebir and Martin Glas and Lazaros Lazaridis",

note = "{\textcopyright} The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.",

year = "2023",

doi = "10.1093/noajnl/vdad090",

language = "English",

volume = "5",

pages = "vdad090",

journal = "NEURO-ONCOLOGY ADVANCES",

issn = "2632-2498",

number = "1",

}

TY - JOUR

T1 - Feasibility and tolerability of trofosfamide and etoposide in progressive glioblastoma

AU - Schmidt, Teresa

AU - Agkatsev, Sarina

AU - Feldheim, Jonas

AU - Oster, Christoph

AU - Blau, Tobias

AU - Sure, Ulrich

AU - Keyvani, Kathy

AU - Kleinschnitz, Christoph

AU - Stuschke, Martin

AU - Herrmann, Ken

AU - Deuschl, Cornelius

AU - Scheffler, Björn

AU - Kebir, Sied

AU - Glas, Martin

AU - Lazaridis, Lazaros

N1 - © The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

PY - 2023

Y1 - 2023

N2 - BACKGROUND: Standard of care treatment options at glioblastoma relapse are still not well defined. Few studies indicate that the combination of trofosfamide plus etoposide may be feasible in pediatric glioblastoma patients. In this retrospective analysis, we determined tolerability and feasibility of combined trofosfamide plus etoposide treatment at disease recurrence of adult glioblastoma patients.METHODS: We collected clinicopathological data from adult progressive glioblastoma patients treated with the combination of trofosfamide and etoposide for more than four weeks (one course). A cohort of patients receiving empiric treatment at the investigators' discretion balanced for tumor entity and canonical prognostic factors served as control.RESULTS: A total of n = 22 progressive glioblastoma patients were eligible for this analysis. Median progression-free survival (3.1 vs 2.3 months, HR: 1.961, 95% CI: 0.9724-3.9560, P = .0274) and median overall survival (9.0 vs 5.7 months, HR: 4.687, 95% CI: 2.034-10.800, P = .0003) were significantly prolonged compared to the control cohort (n = 17). In a multivariable Cox regression analysis, treatment with trofosfamide plus etoposide emerged as a significant prognostic marker regarding progression-free and overall survival. We observed high-grade adverse events in n = 16/22 (73%) patients with hematotoxicity comprising the majority of adverse events (n = 15/16, 94%). Lymphopenia was by far the most commonly observed hematotoxic adverse event (n = 11/15, 73%).CONCLUSIONS: This study provides first indication that the combination of trofosfamide plus etoposide is safe in adult glioblastoma patients. The observed survival outcomes might suggest potential beneficial effects. Our data provide a reasonable rationale for follow-up of a larger cohort in a prospective trial.

AB - BACKGROUND: Standard of care treatment options at glioblastoma relapse are still not well defined. Few studies indicate that the combination of trofosfamide plus etoposide may be feasible in pediatric glioblastoma patients. In this retrospective analysis, we determined tolerability and feasibility of combined trofosfamide plus etoposide treatment at disease recurrence of adult glioblastoma patients.METHODS: We collected clinicopathological data from adult progressive glioblastoma patients treated with the combination of trofosfamide and etoposide for more than four weeks (one course). A cohort of patients receiving empiric treatment at the investigators' discretion balanced for tumor entity and canonical prognostic factors served as control.RESULTS: A total of n = 22 progressive glioblastoma patients were eligible for this analysis. Median progression-free survival (3.1 vs 2.3 months, HR: 1.961, 95% CI: 0.9724-3.9560, P = .0274) and median overall survival (9.0 vs 5.7 months, HR: 4.687, 95% CI: 2.034-10.800, P = .0003) were significantly prolonged compared to the control cohort (n = 17). In a multivariable Cox regression analysis, treatment with trofosfamide plus etoposide emerged as a significant prognostic marker regarding progression-free and overall survival. We observed high-grade adverse events in n = 16/22 (73%) patients with hematotoxicity comprising the majority of adverse events (n = 15/16, 94%). Lymphopenia was by far the most commonly observed hematotoxic adverse event (n = 11/15, 73%).CONCLUSIONS: This study provides first indication that the combination of trofosfamide plus etoposide is safe in adult glioblastoma patients. The observed survival outcomes might suggest potential beneficial effects. Our data provide a reasonable rationale for follow-up of a larger cohort in a prospective trial.

U2 - 10.1093/noajnl/vdad090

DO - 10.1093/noajnl/vdad090

M3 - Original Article

C2 - 37547266

SN - 2632-2498

VL - 5

SP - vdad090

JO - NEURO-ONCOLOGY ADVANCES

JF - NEURO-ONCOLOGY ADVANCES

IS - 1

ER -

Feasibility and tolerability of trofosfamide and etoposide in progressive glioblastoma

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