Chemosensitized radiosurgery for recurrent brain metastases

Area of Science:

• Neuro-oncology
• Radiation oncology
• Clinical pharmacology

Background:

• Temozolomide (TMZ) penetrates the blood-brain barrier and sensitizes brain tumors to radiation.
• Limited prospective data exist on TMZ safety with stereotactic radiosurgery (SRS) for brain metastases.

Purpose of the Study:

• To evaluate the safety and tolerability of escalating doses of temozolomide administered prior to SRS.
• To assess local control and survival outcomes in patients with recurrent brain metastases.

Main Methods:

• Phase I trial enrolling patients with recurrent brain metastases and Karnofsky performance scale score ≥60 %.
• Sequential cohorts received temozolomide (100, 150, or 200 mg/(m(2) day) for 5 days) followed by SRS on day 5.
• SRS dose varied based on target lesion diameter (15-21 Gy).

Main Results:

• 26 subjects and 49 lesions were treated; median metastases 1.5, median diameter 21 mm.
• Most common adverse events were nausea and vomiting (23%); no Grade 3-4 toxicities observed.
• Median overall survival was 10.2 months; crude local control was 87.5%.

Conclusions:

• Temozolomide up to 200 mg/(m(2) day) × 5 days prior to SRS is well-tolerated in patients with recurrent brain metastases.
• No dose-limiting toxicities were identified.
• High local control rates (>80%) were achieved.