Dose-dense temozolomide for recurrent high-grade gliomas: a single-center retrospective study

• Published in: Medical oncology (Northwood, London, England) Vol. 35; no. 10; pp. 136 - 8
• Main Authors: Garcia, Catherine R., Slone, Stacey A., Morgan, Rachael M., Gruber, Lindsey, Kumar, Sameera S., Lightner, Donita D., Villano, John L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2018; Springer Nature B.V
• Subjects: Adult; Antineoplastic Agents, Alkylating - administration & dosage; Brain Neoplasms - diagnosis; Brain Neoplasms - drug therapy; Dose-Response Relationship, Drug; Female; Glioma; Glioma - diagnosis; Glioma - drug therapy; Hematology; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Neoplasm Grading - methods; Neoplasm Grading - trends; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - drug therapy; Oncology; Original Paper; Pathology; Retrospective Studies; Survival Rate - trends; Targeted cancer therapy; Temozolomide - administration & dosage; Recurrence; Prognosis; High-grade gliomas; Dose-dense temozolomide
• ISSN: 1357-0560; 1559-131X
• DOI: 10.1007/s12032-018-1198-0

There are limited treatment modalities after high-grade gliomas recurrence. MGMT depletion modulated by dose-dense temozolomide (ddTMZ) remains a debated therapy for initial TMZ responders. Patients were selected retrospectively from our practice with diagnosis of high-grade gliomas (WHO grade III or IV), and were followed since the start of ddTMZ until death or change of therapy. Twenty-one patients were reviewed, with a median age of 47 (25–61) years and a median of 5.8 (1.5–38.8) cycles of ddTMZ. The majority were males (71.4%). Sixty-six percent received 21 on/28 off ddTMZ schedule, 28.6% daily, and 1 patient received a 7 days on/7 days off schedule. IDH mutation status was available for 18 (85.7%) patients, with 7 (33.3%) IDH mutant and 11 (52.5%) IDH wild type. MGMT methylation was assessed in 6 (28.6%) of the patients, being MGMT methylated in 3 (14.3%) patients, and non-methylated in 3 (14.3%) patients. The majority of patients (57.1%) were receiving ddTMZ in addition to other forms of therapy, including either bevacizumab (38.1%) or tumor-treating fields (TTFields) (19.1%). Overall ddTMZ was well tolerated, with few adverse events reported. The estimated median overall survival after ddTMZ start was 11 months. Median progression-free survival (PFS) was 6 months. Outcomes did not vary between patients receiving ddTMZ alone or those using TTFields or bevacizumab as concomitant therapy, but there was a trend to longer survival with the use of concomitant TTFields. Our results demonstrate benefit of ddTMZ after previous treatment with standard TMZ dosing with no apparent increase in treatment-related toxicities. In summary, ddTMZ should be considered in TMZ responsive patients and warrants further investigation.