Temozolomide for high grade glioma.

Area of Science:

• Neuro-oncology
• Medical Oncology
• Clinical Trials

Background:

• High-grade glioma (HGG) is an aggressive brain cancer requiring effective treatment strategies.
• Temozolomide is an oral chemotherapy agent known for brain penetration and a purportedly low adverse event profile.

Purpose of the Study:

• To evaluate the efficacy of temozolomide in treating high-grade glioma (HGG) in both primary and recurrent disease settings.
• To compare temozolomide-based treatments against standard therapies, including radiotherapy and other chemotherapies.

Main Methods:

• Systematic review of randomized controlled trials (RCTs) identified through comprehensive database searches (CENTRAL, MEDLINE, EMBASE, etc.) and handsearching.
• Included patients with histologically proven HGG of all ages, comparing temozolomide interventions with control groups (no chemotherapy, non-temozolomide chemotherapy, or different dosing).
• Outcome measures focused on overall survival (OS), progression-free survival (PFS), quality of life (QoL), and adverse events, with data extracted by two independent reviewers.

Main Results:

• For primary treatment of glioblastoma multiforme (GBM), temozolomide combined with radiotherapy significantly increased OS and PFS compared to radiotherapy alone, particularly when administered concomitantly and adjuvantly.
• In recurrent HGG, temozolomide did not improve OS versus standard chemotherapy but showed increased PFS in a subgroup of grade IV GBM tumors.
• In elderly patients, temozolomide monotherapy showed similar OS and PFS to radiotherapy alone, though with a higher incidence of adverse events.

Conclusions:

• Temozolomide is an effective primary therapy for GBM when used with radiotherapy in both concomitant and adjuvant phases, prolonging survival and delaying progression with no impact on QoL but increased early adverse events.
• In recurrent GBM, temozolomide improves time-to-progression and may benefit QoL without increasing adverse events, but does not improve overall survival compared to standard chemotherapy.
• In elderly patients, temozolomide monotherapy is comparable to radiotherapy for OS and PFS but associated with more adverse events.