A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma

Gately, L.; Mesía, C.; Sepúlveda, J. M.; del Barco, S.; Pineda, E.; Gironés, R.; Fuster, J.; Hong, W.; Dumas, M.; Gill, S.; Navarro, L. M.; Herrero, A.; Dowling, A.; de las Peñas, R.; Vaz, M. A.; Alonso, M.; Lwin, Z.; Harrup, R.; Peralta, S.; Long, A.; Perez-Segura, P.; Ahern, E.; Garate, C. O.; Wong, M.; Campbell, R.; Cuff, K.; Jennens, R.; Gallego, O.; Underhill, C.; Martinez-Garcia, M.; Covela, M.; Cooper, A.; Brown, S.; Rosenthal, M.; Torres, J.; Collins, I. M.; Gibbs, P.; Balana, C.

doi:10.1007/s11060-023-04513-1

Cited by 2 publications

(1 citation statement)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Radiotherapy has been shown to upregulate MGMT, whereas prolonged exposure to alkylating agents may suppress MGMT activity making the cells more susceptible to TMZ [ 257 ]. Nevertheless, several trials ( Table 2 ) evidence that extending post-radiation TMZ from 6 to 12 months does not improve PFS6 and is associated with greater toxicity, functional deterioration, and poorer quality of life [ 257 , 258 ].…”

Section: Present Therapy and Challengesmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

View full text Add to dashboard Cite

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood–brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.

show abstract

Section: Present Therapy and Challengesmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

Extended cycles of adjuvant temozolomide improves survival outcomes in glioblastoma: a retrospective analysis

Xu,

Yu,

Wang

et al. 2024

J Cancer Metastasis Treat

View full text Add to dashboard Cite

Aim: Standard treatment includes post-surgical chemoradiotherapy and adjuvant temozolomide (TMZ) for glioblastoma (GBM). There is no consensus on the optimal duration for adjuvant TMZ. This study assessed whether prolonging adjuvant TMZ improved survival outcomes. Methods: We retrospectively analyzed data of GBM patients who met inclusion criteria at our institute from September 2013 to December 2022. Patients who received 6 cycles of maintenance TMZ constituted the standard group, whereas those who underwent > 6 cycles were classified into the extended group. Kaplan-Meier method was used to estimate the median progression-free survival (PFS) and overall survival (OS). Independent predictors of OS and PFS were explored by Cox regression analyses. Results: 100 patients were enrolled. Extended adjuvant TMZ significantly improved OS (28.0 vs. 10.0 months, P < 0.001) and PFS (22.0 vs. 8.0 months, P < 0.001) in newly diagnosed GBM patients. Subgroup analysis showed that patients with MGMT promoter methylation who received > 6 cycles of adjuvant TMZ experienced a significant increase in OS (34.0 vs. 9.0 months, P < 0.001) and PFS (26.0 vs. 9.0 months, P = 0.008). Additionally, in the extended group, patients with MGMT promoter methylation had better survival outcomes compared to MGMT promoter unmethylated patients (OS: 34.0 vs. 17.0 months, P = 0.013; PFS: 26.0 vs. 12.0 months, P = 0.025). In patients with solitary GBM, extended adjuvant TMZ resulted in better OS (11.0 vs. 32 months, P = 0.007) and PFS (9.0 vs. 24.0 months, P < 0.001). For patients with multiple GBM, undergoing six or more cycles of adjuvant TMZ did not significantly impact OS (P = 0.100) and PFS (P = 0.067). The Karnofsky Performance Status (KPS) is employed to assess the health condition of surgical patients. Patients with KPS > 70 exhibited better survival outcomes in the extended group. Nausea and vomiting were the main adverse events reported in both cohorts. However, fatigue emerged as the most severe side effect, specifically within the extended group. Conclusion: This study indicated that prolonged adjuvant TMZ significantly enhanced OS and PFS in GBM, and the adverse events were acceptable. The benefits were particularly notable in those with MGMT promoter methylation, solitary GBM, and high KPS. The optimal cycles of adjuvant TMZ require large prospective studies to further validate and identify which patient groups benefit the most based on molecular subtyping and clinical characteristics.

show abstract

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma

Cited by 2 publications

References 27 publications

Glioblastoma Therapy: Past, Present and Future

Glioblastoma Therapy: Past, Present and Future

Extended cycles of adjuvant temozolomide improves survival outcomes in glioblastoma: a retrospective analysis

Contact Info

Product

Resources

About