Combination of paclitaxel thermal gel depot with temozolomide and radiotherapy significantly prolongs survival in an experimental rodent glioma model.

OncoGel™ incorporates paclitaxel, a mitotic inhibitor, into ReGel™, a thermosensitive gel depot system to provide local delivery, enhance efficacy and limit systemic toxicity. In previous studies the alkylating agent temozolomide (TMZ) incorporated into a polymer, pCPP:SA, also for local delivery, and OncoGel were individually shown to increase efficacy in a rat glioma model. We investigated the effects of OncoGel with oral TMZ or locally delivered TMZ polymer, with and without radiotherapy (XRT) in rats with intracranial gliosarcoma. Eighty-nine animals were intracranially implanted with a 9L gliosarcoma tumor and divided into 12 groups that received various combinations of 4 treatment options; OncoGel 6.3 mg/ml (Day 0), 20 Gy XRT (Day 5), 50 % TMZ-pCPP:SA (Day 5), or oral TMZ (50 mg/kg, qd, Days 5-9). Animals were followed for survival for 120 days. Median survival for untreated controls, XRT alone or oral TMZ alone was 15, 19 and 28 days, respectively. OncoGel 6.3 or TMZ polymer alone extended median survival to 33 and 35 days, respectively (p = 0.0005; p < 0.0001, vs. untreated controls) with 50 % living greater than 120 days (LTS) in both groups. Oral TMZ/XRT extended median survival to 36 days (p = 0.0002), with no LTS. The group that received OncoGel and Oral TMZ did not reach median survival with 57 % LTS (p = 0.0002). All other combination groups [OncoGel/XRT], [TMZ polymer/XRT], [OncoGel/TMZ polymer], [OncoGel/TMZ polymer/XRT], and [OncoGel/oral TMZ/XRT] yielded greater than 50 % LTS (p < 0.0001 for each combination as compared to controls), therefore median survival was not reached. OncoGel/TMZ polymer and OncoGel/oral TMZ/XRT had 100 % LTS (p < 0.0001 and p = 0.0001 vs. oral TMZ/XRT, respectively). These results indicate that OncoGel given locally with oral or locally delivered TMZ and/or XRT significantly increased the number of LTS and improved median survival compared to oral TMZ and XRT given alone or in combination in a rodent intracranial gliosarcoma model.

Planning extent of resection in epilepsy: limited versus large resections.

Aggressive versus limited resection is an often-debated topic in epilepsy surgery. There are two inherent questions within this debate: (1) Can a more limited resection yield seizure freedom rates similar to those afforded by wider/more aggressive resection, with lower rates of neurological complications? (2) Does wider/more aggressive resection increase seizure freedom rates, with tolerable neurological complications rates? Further, if more limited resection has a lower seizure freedom rate, but fewer complications, is quality of life better or worse than that following a wider/more aggressive resection that increases seizure freedom rate but yields a higher complication rate? Here, we review the literature to address these questions. Because most studies are retrospective observational studies, with limited statistical power to draw strong conclusions, there is a need for more randomized prospective multicenter clinical trials incorporating advances in technique for identifying the seizure onset zone (e.g., subtractive ictal SPECT) and tissue at risk (e.g., diffusion tensor imaging) to inform this discussion.