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Temozolomide for treating brain metastases
1Department of Neurology at Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Abstract:
The metastasis of solid tumors to the brain is associated with a poor prognosis despite aggressive treatment. Available treatment options are limited, as many chemotherapeutic agents do not penetrate the blood-brain barrier. Temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) is a novel chemotherapeutic agent with a good safety profile that crosses the blood-brain barrier and has shown activity against many human solid tumors. In two phase II trials of temozolomide in heavily pretreated patients with various solid tumor brain metastases, temozolomide was safe and generally well tolerated and showed clinical activity, with three partial responses and 19 disease stabilizations. Results of a third randomized phase II trial of concurrent administration of temozolomide and radiation therapy followed by adjuvant temozolomide therapy compared with radiation alone showed a higher rate of complete and partial responses (objective response of 96% v 67%) and significantly more complete responses (38% v 33%, P =.017), primarily in patients with newly diagnosed brain and lung metastases.
Insights
Temozolomide effectively crosses the blood-brain barrier, showing promise for brain metastases. Clinical trials indicate it is safe and well-tolerated, with significant response rates when combined with radiation therapy.
Area of Science:
- Oncology
- Neuro-oncology
- Pharmacology
Background:
- Brain metastases from solid tumors have a poor prognosis.
- Limited treatment options exist due to the blood-brain barrier (BBB).
- Chemotherapeutic agents often fail to penetrate the BBB.
Observation:
- Temozolomide is a novel chemotherapeutic agent.
- Temozolomide demonstrates a good safety profile.
- Temozolomide effectively crosses the BBB and shows activity against solid tumors.
Findings:
- In Phase II trials, temozolomide was safe and well-tolerated in patients with brain metastases.
- Clinical activity was observed, including partial responses and disease stabilization.
- A randomized Phase II trial showed higher objective response rates (96% vs. 67%) with concurrent temozolomide and radiation therapy compared to radiation alone.
Implications:
- Temozolomide represents a viable treatment option for brain metastases.
- Combination therapy with radiation may improve treatment outcomes.
- Further research into temozolomide for brain metastases is warranted.