d,l-Methadone does not improve radio- and chemotherapy in glioblastoma in vitro

Purpose Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. Median survival of glioblastoma patients under standard therapy including radiotherapy and chemotherapy using temozolomide (TMZ) is 14.6 months. As cell culture experiments combining d,l -methadone with doxo...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 2019-06, Vol.83 (6), p.1017-1024
Main Authors: Oppermann, Henry, Matusova, Martina, Glasow, Annegret, Dietterle, Johannes, Baran-Schmidt, Rainer, Neumann, Karsten, Meixensberger, Jürgen, Gaunitz, Frank
Format: Article
Language:English
Subjects:
Adult
Aged
Analgesics, Opioid - administration & dosage
Analgesics, Opioid - pharmacology
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Biotechnology
Brain cancer
Brain Neoplasms - therapy
Cancer Research
Cell culture
Cell Survival - drug effects
Cell viability
Central nervous system
Chemotherapy
Doxorubicin
Doxorubicin - administration & dosage
Female
Fibroblasts
Glioblastoma
Glioblastoma - therapy
Glioblastoma cells
Humans
In Vitro Techniques
Irradiation
Lysates
Male
Medicine
Medicine & Public Health
Methadone
Methadone - administration & dosage
Methadone - pharmacology
Middle Aged
Narcotics
Oncology
Opioids
Original Article
Patients
Pharmacology/Toxicology
Radiation therapy
Temozolomide
Temozolomide - administration & dosage
Tumors
X-rays
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Summary:Purpose Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. Median survival of glioblastoma patients under standard therapy including radiotherapy and chemotherapy using temozolomide (TMZ) is 14.6 months. As cell culture experiments combining d,l -methadone with doxorubicin demonstrated an increased reduction of cell viability of glioblastoma cells, the opioid has been discussed as a drug for the treatment of GBM. Despite lack of clinical and experimental evidence that d,l -methadone in combination with standard therapy will be beneficial, an increasing number of tumor patients medicating themselves with d,l -methadone present to the hospitals in Germany. Methods As a first step towards understanding whether d,l -methadone may increase the efficacy of standard therapy, we used a cell culture model of primary GBM and fibroblast cell cultures derived from GBM patients. The cultures were treated with different concentrations of d,l -methadone in combination with X-irradiation, TMZ or both. Cell viability was determined by measuring ATP in cell lysates and dehydrogenase activity in living cells. Results When only treated with d,l -methadone, 1 µM of the opioid was sufficient to reduce viability of fibroblasts, whereas 10 µM was needed to significantly reduce glioblastoma cell viability. In addition, d,l -methadone did not improve the anti-neoplastic effects of X-irradiation, temozolomide or both. Conclusions As d,l -methadone reduces glioblastoma cell viability only when concentrations are used that had been reported to be toxic to patients and as there were no interactions observable combining it with standard therapy, a recommendation for the use of d,l -methadone in glioblastoma therapy cannot be given.
ISSN:0344-5704
1432-0843
DOI:10.1007/s00280-019-03816-3