Safety and Tolerance of D,L-Methadone in Combination with Chemotherapy in Patients with Glioma.
D,L-Methadone increases sensitivity toward chemotherapy of different tumor cell populations. We evaluated the safety and tolerance of additional use of D,L-methadone in patients with glioma in combination with chemotherapy.



The dosage, duration of therapy and side-effects related to D,L-methadone were recorded in 27 patients. Toxicity was assessed accordingly to the Common Toxicity Criteria (CTC) of the National Cancer Institute. Progression-free survival at 6 months (PFS-6) was assessed.



A total of 13 patients reported grade 1-3 nausea at the beginning of the D,L-methadone therapy. Four patients reported persistent side-effects of nausea (CTC Grade 2, n=1) and obstipation (CTC grade 2-3, n=3). PFS-6 of patients with glioblastoma was 80% in those with non-methylated O6-methylguanine-DNA methyltransferase (MGMT) (n=5) and 100% in those with MGMT methylation (n=7).



D,L-methadone can be safely combined with standard glioma chemotherapy without increasing the risk of toxicity or vegetative symptoms such as tachycardia, sweating and restlessness. PFS-6 in patients with primary glioblastoma treated this way seems to be at least comparable to that of historic controls.
Department of Neurosurgery, Charité University of Berlin, Berlin, Germany julia.onken@charite.de.|Berlin Institute of Health, Berlin, Germany.
Julia
J
Onken
Center of Biomedical Research, University of Ulm, Ulm, Germany.|Institute for Legal Medicine, University of Ulm, Ulm, Germany.
Claudia
C
Friesen
Department of Neurosurgery, Charité University of Berlin, Berlin, Germany.
Peter
P
Vajkoczy
Department of Neurosurgery, Charité University of Berlin, Berlin, Germany.
Martin
M
Misch
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002986:Clinical Trials as Topic; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage*; D008875:Middle Aged; D061214:Patient Safety; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics
D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D008691:Methadone
D,L-Methadone; chemotherapy; efficiency; malignant glioma; safety