Artesunate in glioblastoma therapy: Case reports and review of clinical studies.
Artesunate
Cancer therapy
Glioblastoma
Temozolomide
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
12 Dec 2023
12 Dec 2023
Historique:
received:
12
09
2023
revised:
22
11
2023
accepted:
10
12
2023
medline:
25
12
2023
pubmed:
25
12
2023
entrez:
24
12
2023
Statut:
aheadofprint
Résumé
Artesunate, a derivative of the active ingredient artemisinin from Artemisia annua L. used for centuries in the traditional Chinese medicine, is being applied as front-line drug in malaria treatment. As it is cytotoxic for cancer cells, trials are ongoing to include this drug as supplement in cancer therapy. In glioblastoma cells, artesunate was shown to induce oxidative stress, DNA base damage and double-strand breaks (DSBs), apoptosis, and necroptosis. It also inhibits DNA repair functions and bears senolytic activity. Compared to ionizing radiation, DNA damages accumulate over the whole exposure period, which makes the agent unique in its genotoxic profile. Artesunate has been used in adjuvant therapy of various cancers. As artesunate has been used in adjuvant therapy of different types of cancer and clinical trials are lacking in brain cancer, we investigated its activity in glioma patients with focus on possible side effects. Between 2014 and 2020, twelve patients were treated with artesunate for relapsing glioma and analyzed retrospectively: 8 males and 4 females, median age 45 years. 4 glioblastomas WHO grade 4, 5 astrocytomas WHO grade 3, 3 oligodendrogliomas grade 2 or 3. All patients were pretreated with radiation and temozolomide-based chemotherapy. Artesunate 100 mg was applied twice daily p.o. combined with dose-dense temozolomide alone (100 mg/m Apart from one transient grade 3 hematological toxicity, artesunate was well tolerated. No liver toxicity was observed. While 8 patients with late stage of the disease had a median survival of 5 months after initiation of artesunate treatment, 4 patients with treatment for remission maintenance showed a median survival of 46 months. We also review clinical trials that have been performed in other cancers where artesunate was included in the treatment regimen. Artesunate administered at a dose of 2 × 100 mg/day was without harmful side effects, even if combined with alkylating agents used in glioma therapy. Thus, the phytochemical, which is also utilized as food supplement, is an interesting, well tolerated supportive agent useful for long-term maintenance treatment. Being itself cytotoxic on glioblastoma cells and enhancing the cytotoxicity of temozolomide as well as in view of its senolytic activity, artesunate has clearly a potential to enhance the efficacy of malignant brain cancer therapy.
Sections du résumé
BACKGROUND
BACKGROUND
Artesunate, a derivative of the active ingredient artemisinin from Artemisia annua L. used for centuries in the traditional Chinese medicine, is being applied as front-line drug in malaria treatment. As it is cytotoxic for cancer cells, trials are ongoing to include this drug as supplement in cancer therapy. In glioblastoma cells, artesunate was shown to induce oxidative stress, DNA base damage and double-strand breaks (DSBs), apoptosis, and necroptosis. It also inhibits DNA repair functions and bears senolytic activity. Compared to ionizing radiation, DNA damages accumulate over the whole exposure period, which makes the agent unique in its genotoxic profile. Artesunate has been used in adjuvant therapy of various cancers.
PURPOSE
OBJECTIVE
As artesunate has been used in adjuvant therapy of different types of cancer and clinical trials are lacking in brain cancer, we investigated its activity in glioma patients with focus on possible side effects.
STUDY DESIGN
METHODS
Between 2014 and 2020, twelve patients were treated with artesunate for relapsing glioma and analyzed retrospectively: 8 males and 4 females, median age 45 years.
HISTOLOGY
RESULTS
4 glioblastomas WHO grade 4, 5 astrocytomas WHO grade 3, 3 oligodendrogliomas grade 2 or 3. All patients were pretreated with radiation and temozolomide-based chemotherapy. Artesunate 100 mg was applied twice daily p.o. combined with dose-dense temozolomide alone (100 mg/m
RESULTS
RESULTS
Apart from one transient grade 3 hematological toxicity, artesunate was well tolerated. No liver toxicity was observed. While 8 patients with late stage of the disease had a median survival of 5 months after initiation of artesunate treatment, 4 patients with treatment for remission maintenance showed a median survival of 46 months. We also review clinical trials that have been performed in other cancers where artesunate was included in the treatment regimen.
CONCLUSIONS
CONCLUSIONS
Artesunate administered at a dose of 2 × 100 mg/day was without harmful side effects, even if combined with alkylating agents used in glioma therapy. Thus, the phytochemical, which is also utilized as food supplement, is an interesting, well tolerated supportive agent useful for long-term maintenance treatment. Being itself cytotoxic on glioblastoma cells and enhancing the cytotoxicity of temozolomide as well as in view of its senolytic activity, artesunate has clearly a potential to enhance the efficacy of malignant brain cancer therapy.
Identifiants
pubmed: 38142662
pii: S0944-7113(23)00632-3
doi: 10.1016/j.phymed.2023.155274
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
155274Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Authors declare there is no conflict of interes