Efficacy
In the NRG CC001 phase III study, 518 patients with brain metastases were randomised to hippocampal avoidance whole brain radiation therapy (HA-WBRT) plus memantine, or whole brain radiation therapy (WBRT) plus memantine.r The prescribed WBRT dose was 30 Gy in 10 fractions for both arms. Follow-up for living patients was a median of 7.9 months. The primary endpoint was “cognitive failure” defined as cognitive decline determined by the reliable change index on at least one cognitive test. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted HR = 0.74, 95% CI:0.58-0.95, p = 0.02). This study found less deterioration in executive function at four months (23.3% versus 40.4%, p = 0.01), learning at six months (11.5% versus 24.7%, p = 0.049) and memory at six months (16.4% versus 33.3%, p = 0.02). Treatment arms did not differ significantly in overall survival, intracranial progression-free survival, or toxicity.
The RTOG 0933 phase II prospective study suggested a reduced risk of cognitive dysfunction in patients with brain metastases receiving HA-WBRT.r Patients received 30 Gy in 10 fractions. Four months after treatment, only 7% of patients receiving HA-WBRT had a decline in Hopkins verbal learning test delayed recall, compared to 30% in a historical control group.