OBJECTIVES: Malignant gliomas are highly proliferative, invasive tumors that are resistant to conventional treatment and are typically accompanied by progressive physical and mental debilitation. We evaluated neurocognitive functioning (NCF) and quality of life (QOL) as part of a prospective Phase Ib dose-escalation study of topotecan by CED in patients with recurrent gliomas. METHODS: Secondary data analysis was conducted on the 16 patients enrolled on the Phase Ib study. Independent-sample t-tests were used to explore differences. Patients received serial assessments at baseline, 1-, 2-, 3-, and 4-months post-treatment. NCF and QOL were assessed using the HeadMinder Cognitive Stability Index and the SF-36, respectively.  RESULTS: Patients were predominantly male (68.7%) with a median age of 50 years (Range=22-71 years).  Tumor volume and total infused dose of topotecan were not associated with any of the outcome variables. NCF was better for early responders (ERs) than patients with progressive disease (PD) or pseudoprogression (PP). Processing speed for ERs (n=4) averaged over the follow-up period was significantly higher (z=1.95 SD) than patients with PD (n=5; z=-0.61 SD) (p=0.006).  Similarly, change in response time was better for ERs compared to those with PD (z=4.40 SD; z=-0.52, respectively; p=0.04).  At baseline, SF-36 results for physical and mental QOL were within normal limits.  Relative to baseline, average change in SF-36 scores post-treatment suggest that overall mental QOL was significantly higher for ERs (MCS change score=5.04) than patients with PD (MCS change score=-6.48) (p=0.02), reflecting better emotional well-being. Average change in physical QOL was not significantly different between ERs, PD or PP. CONCLUSIONS: These results provide the beginning framework to better understand NCF/QOL outcomes in patients with recurrent malignant gliomas treated with topotecan by CED.  Continued monitoring of these outcomes will be important in the phase II trial to assess treatment efficacy and impact on NCF and QOL.