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Hepatotoxicity by combination treatment of temozolomide, artesunate and Chinese herbs in a glioblastoma multiforme patient: case report review of the literature

  • Organ Toxicity and Mechanisms
  • Published:
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Abstract

Glioblastoma multiforme (GBM) represents an aggressive tumor type with poor prognosis. The majority of GBM patients cannot be cured. There is high willingness among patients for the compassionate use of non-approved medications, which might occasionally lead to profound toxicity. A 65-year-old patient with glioblastoma multiforme (GBM) has been treated with radiochemotherapy including temozolomide (TMZ) after surgery. The treatment outcome was evaluated as stable disease with a tendency to slow tumor progression. In addition to standard medication (ondansetron, valproic acid, levetiracetam, lorazepam, clobazam), the patient took the antimalarial drug artesunate (ART) and a decoction of Chinese herbs (Coptis chinensis, Siegesbeckia orientalis, Artemisia scoparia, Dictamnus dasycarpus). In consequence, the clinical status deteriorated. Elevated liver enzymes were noted with peak values of 238 U/L (GPT/ALAT), 226 U/L (GOT/ASAT), and 347 U/L (γ-GT), respectively. After cessation of ART and Chinese herbs, the values returned back to normal and the patient felt well again. In the literature, hepatotoxicity is well documented for TMZ, but is very rare for ART. Among the Chinese herbs used, Dictamnus dasycarpus has been reported to induce liver injury. Additional medication included valproic acid and levetiracetam, which are also reported to exert hepatotoxicity. While all drugs alone may bear a minor risk for hepatotoxicity, the combination treatment might have caused increased liver enzyme activities. It can be speculated that the combination of these drugs caused liver injury. We conclude that the compassionate use of ART and Chinese herbs is not recommended during standard radiochemotherapy with TMZ for GBM.

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Abbreviations

AGT:

O6-alkylguanine-DNA alkyltransferase

ARS:

Artemisinin

ART:

Artesunate

BER:

DNA base excision repair

CNS:

Central nervous system

DEX:

Dexamethasone

DSB:

Double-strand break

GBM:

Glioblastoma multiforme

GM-CSF:

Granulocyte–monocyte colony-stimulating factor

GST:

Glutathione S-transferase

INF:

Interferon

HR:

Homologous recombination

MGMT:

Methylguanine methyltransferase

MMR, DNA:

Mismatch repair

MTX:

Methotrexate

NHEJ:

Non-homologous end joining

TMZ:

Temozolomide

VCR:

Vincristine

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Authors and Affiliations

  1. Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Staudinger Weg 5, 55128, Mainz, Germany

    Thomas Efferth & Ursula Schöttler

  2. Institute for Infection and Immunity, St. George’s, University of London, London, UK

    Sanjeev Krishna

  3. Department of Radiation Oncology, University Medical Center Mannheim, Mannheim, Germany

    Peter Schmiedek, Frederik Wenz & Frank A. Giordano

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  1. Thomas Efferth
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  2. Ursula Schöttler
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  3. Sanjeev Krishna
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Correspondence to Thomas Efferth.

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Efferth, T., Schöttler, U., Krishna, S. et al. Hepatotoxicity by combination treatment of temozolomide, artesunate and Chinese herbs in a glioblastoma multiforme patient: case report review of the literature. Arch Toxicol 91, 1833–1846 (2017). https://doi.org/10.1007/s00204-016-1810-z

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