Thrombocytopenia limits the feasibility of salvage lomustine chemotherapy in recurrent glioblastoma: a secondary analysis of EORTC 26101

Emilie Le Rhun*, Felix Boakye Oppong, Martin van den Bent, Wolfgang Wick, Alba A. Brandes, Martin JB Taphoorn, Michael Platten, Ahmed Idbaih, Paul M. Clement, Matthias Preusser, Vassilis Golfinopoulos, Thierry Gorlia, Michael Weller

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background: Thrombocytopenia represents the main cause of stopping alkylating chemotherapy for toxicity. Here, we explored the incidence, and the consequences for treatment exposure and survival, of thrombocytopenia induced by lomustine in recurrent glioblastoma. Methods: We performed a retrospective analysis of the associations of thrombocytopenia with treatment delivery and outcome in EORTC 26101, a randomised trial designed to define the role of lomustine versus bevacizumab versus their combination in recurrent glioblastoma. Results: A total of 225 patients were treated with lomustine alone (median 1 cycle) (group 1) and 283 patients were treated with lomustine plus bevacizumab (median 3 lomustine cycles) (group 2). Among cycle delays and dose reductions of lomustine for toxicity, thrombocytopenia was the leading cause. Among 129 patients (57%) of group 1 and 187 patients (66%) of group 2 experiencing at least one episode of thrombocytopenia, 36 patients (16%) in group 1 and 93 (33%) in group 2 had their treatment modified because of thrombocytopenia. Lomustine was discontinued for thrombocytopenia in 16 patients (7.1%) in group 1 and in 38 patients (13.4%) in group 2. On adjusted analysis accounting for major prognostic factors, dose modification induced by thrombocytopenia was associated with inferior progression-free survival in patients with MGMT promoter-methylated tumours in groups 1 and 2. This effect was noted for overall survival, too, but only for group 2 patients. Conclusion: Drug-induced thrombocytopenia is a major limitation to adequate exposure to lomustine chemotherapy in recurrent glioblastoma. Mitigating thrombocytopenia to enhance lomustine exposure might improve outcome in patients with MGMT promoter-methylated tumours.

Original languageEnglish
Pages (from-to)13-22
Number of pages10
JournalEuropean Journal of Cancer
Volume178
Early online date12 Nov 2022
DOIs
Publication statusPublished - 1 Jan 2023

Bibliographical note

Funding Information:
This publication was supported by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group. We are grateful to F. Hoffmann - La Roche from Switzerland for supporting the independent EORTC Study 26101. Felix B. Oppong's work as Fellow at EORTC Headquarters was supported by a grant from the EORTC Brain Tumor Group.


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