What is the role of Temozolomide (generic name) in the treatment of Glioblastoma?

From the Guidelines

Temozolomide is a standard first-line treatment for glioblastoma, typically used alongside surgery and radiation therapy, and the most recent evidence supports its use in this context 1. The standard regimen involves concurrent temozolomide (75 mg/m² daily) during radiation therapy (usually 6 weeks), followed by adjuvant temozolomide (150-200 mg/m² for 5 days every 28-day cycle) for 6-12 months. This approach has been shown to improve both progression-free and overall survival compared to radiation alone, as demonstrated in a study published in the Journal of Clinical Oncology 1. Temozolomide works by alkylating DNA, which damages the genetic material of rapidly dividing cancer cells and triggers cell death. The drug's effectiveness is enhanced in patients whose tumors have methylation of the MGMT gene promoter, as these tumors are less able to repair the DNA damage caused by temozolomide. Some key points to consider when using temozolomide for glioblastoma include:

• The importance of concurrent and adjuvant temozolomide in improving overall survival and progression-free survival 1
• The role of MGMT promoter methylation in predicting response to temozolomide 1
• The potential for hypofractionated radiotherapy to be used in combination with temozolomide in certain patient populations 1 Common side effects of temozolomide include:
• Nausea
• Fatigue
• Constipation
• Myelosuppression (particularly thrombocytopenia and neutropenia) These side effects require regular blood count monitoring, and antiemetics are typically prescribed to manage nausea. While not curative, temozolomide remains a cornerstone of glioblastoma treatment as part of a multimodal approach to this aggressive brain cancer.

From the FDA Drug Label

Temozolomide capsules are an alkylating drug indicated for the treatment of adult patients with: Newly diagnosed glioblastoma multiforme (GBM) concomitantly with radiotherapy and then as maintenance treatment. Temozolomide capsules are indicated for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment.

Temozolomide is indicated for the treatment of glioblastoma, specifically for newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment 2, 2, 2.

• The recommended dosage is 75 mg/m2 for 42 days concomitant with focal radiotherapy, followed by an initial maintenance dose of 150 mg/m2 once daily for Days 1 to 5 of a 28-day cycle of temozolomide capsules for 6 cycles 2.
• Key warnings and precautions include myelosuppression, cases of myelodysplastic syndrome and secondary malignancies, pneumocystis pneumonia, hepatotoxicity, and fetal harm 2.

From the Research

Temozolomide for Glioblastoma

• Temozolomide is a first-line treatment for newly diagnosed glioblastoma, as stated in the study by 3.
• The standard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide, as mentioned in the study by 4.
• The addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma, but improved progression-free survival and maintained baseline quality of life and performance status, as reported in the study by 4.

Efficacy of Temozolomide

• Temozolomide improved survival in older patients with glioblastoma, anaplastic gliomas regardless of 1p/19q deletion status, and progressive ependymomas, as stated in the study by 3.
• Temozolomide afforded less toxicity and comparable efficacy to radiation in high-risk low-grade gliomas and to platinum-based chemotherapy in pediatric high-grade gliomas, as mentioned in the study by 3.
• Long-term therapy with temozolomide is a feasible option for newly diagnosed glioblastoma, with statistically significant data confirming that median survival correlates with MGMT promoter methylation status as well as with the number of temozolomide cycles administered, as reported in the study by 5.

Combination Therapy

• The combination of bevacizumab, radiotherapy, and temozolomide for the treatment of newly diagnosed glioblastoma showed improved progression-free survival, but not overall survival, as stated in the study by 4.
• The phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme showed improved progression-free survival without improved overall survival compared to the control group, as reported in the study by 6.

Patient Outcomes

• The median survival for patients with glioblastoma treated with temozolomide and radiotherapy was 15.8 months, with a 2-year survival rate of 35%, as mentioned in the study by 7.
• The long-term survivors, defined as patients who survived at least 12 months after diagnosis, were 51.3% of the total, as reported in the study by 5.
• Patients treated with more than 6 temozolomide cycles had overall survival and progression-free survival that was significantly longer than patients receiving standard treatment, as stated in the study by 5.