Safety and Tolerance of D,L-Methadone in Combination with Chemotherapy in Patients with Glioma.

BACKGROUND/AIM: 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.

PATIENTS AND METHODS: 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.

RESULTS: 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).

CONCLUSION: 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.