1.Local interstitial chemotherapy with sustained release bucladesine in de novo glioblastoma Long survival results with sequential biochemotherapy (local bucladesine polymer [bcl-SR] with fotémustine) in patients with de novo glioblastoma.This clinical study was designed to evaluate the impact ofbiochemotherapy on the time of recurrence of the de novo GBM in patients.In a randomized prospective manner, 50 patients who were diagnosed with the de novo GBM were included in this study.Five different therapy protocols were used.The first group of 10 patients had tumor resection only.The second group assessed had only systemic chemotherapy as 6 intravenous (Ⅳ) infusions of fotémustine after tumor resection.The third group had implantation of bcl-SR pellets.The fourth group received 6 Ⅳ infusions of systemic fotémustine as in the second group in addition to local implantation of bcl-SR pellets.Finally, the fifth group assessed had stereotactic biopsy and implantation ofbcl-SR rods under local anesthesia repeated in 6-month intervals.All groups received irradiation.In this trial of local interstitial biologic therapy with long-acting (4-5 months of release time) bcl-SR, bcl-SR polymers did show a statistically significant delay of recurrence in the treatment of patients with GBM.Best treatment results were obtained from the local bcl-SR with systemic fotémustinetreated group in which survival rate estimated by Kaplan-Meier method was 100% in de novo GBM at 12 months.Moreover, in the last group, mean survival rate was 89.8±25.9 weeks, and 1-,2-,and 3-year survival rates were 100%, 40%, and 10%, respectively.Median survival times of 28, 32, 37,63, and 86 weeks were achieved for the control, fotémustine, bcl-SR, fotémustine with bcl-SR, and repeated stereotactic bcl-SR with fotémustine groups, respectively.In this prospective clinical study conducted on primary GBM cases, although the number of patients was small, there is a significant benefit of local bcl-SR when used in combination with systemic fotémustine therapy (Biochemotherapy) with no adverse effects.2.Efficacy of controlled-release papaverine pellets in preventing symptomatic cerebral vasospasm Vasospasm as a complication of subarachnoid hemorrhage is a major concern in clinical practice.The systemic drugs in current use are of limited value.Topical, intrathecal, or intraarterial papaverine administered during surgical or angiographic procedures is a potent vasodilating drug;however, hypotension limits its systemic application.Local application of papaverine in a biodegradable controlled-or sustained-release matrix is proposed for vasospasm prophylaxis to be used in patients scheduled for aneurysm surgery.Controlled-release papaverine (PapaCR) drug pellets were prepared using the biodegradable aliphatic polymer ester poly(DL-lactide-co-gylcolide) as the carrier matrix.In vitro tests were performed to determine drug kinetics.One hundred seventeen patients, 73 assigned to the control group and 44 assigned to the Papa-CR-treated group, participate in the study.During aneurysm surgery, drug pellets were placed in cisterns over arterial segments.In two patients, cerebrospinal fluid was sampled every 6 hours for the first 5 days through a lumbar catheter that had been inserted at the begininig of aneurysm surgery.The incidence of clinical vasospasm and Glasgow Outcome Scale scores in the patients were evaluated statistically.The results of in vitro studies showed that effective local concentrations ofpapaverine could be maintained for more than 10 days.The first-degree drug-release profile was demonstrated using this design.In clinical vasospasm, and outcome scores were significantly better in patients in the treated group.Local application of controlled-or sustained-release papaverine can be safely used used in preventing vasospasm.