title: Stereotactic injection of DTI-015 into recurrent malignant gliomas: phase I/II trial.
abstract: DTI-015 (BCNU in 100% ethanol) utilizes solvent facilitated perfusion for the intratumoral treatment of gliomas. The ethanol solvent vehicle facilitates a rapid and thorough saturation of the tumor with the dissolved anticancer agent BCNU. We conducted a phase I/II dose escalation study of DTI-015 in 40 heavily pretreated patients with inoperable recurrent malignant glioma. The study goals were to establish a maximally tolerated dose (MTD) for DTI-015 and assess its safety and activity. Patients received stereotactic intratumoral injection of DTI-015 under magnetic resonance imaging guidance. Dose escalation was performed in two phases. First, DTI-015 volume was escalated at a set BCNU concentration of 12.5 mg/ml; second, BCNU mg dose was escalated by increasing BCNU concentration to 30, 45, 60, and 75 mg/ml. A MTD of 5 ml and 240 mg was established. Twenty-five of 28 DTI-015 treatments (89%) using </=MTD were administered safely without producing high-grade drug-related adverse events. Median survival for GBM patients administered DTI-015 at </=MTD was 55 weeks. Magnetic resonance imaging demonstrated stable disease in 72% of evaluable patients with a median of 10.5 weeks. The results suggest that DTI-015 administered at </=MTD is well tolerated and active in patients with inoperable recurrent GBM.
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Hassenbusch
authors.forename: Emilio M
authors.initials: EM
authors.lastname: Nardone
authors.forename: Victor A
authors.initials: VA
authors.lastname: Levin
authors.forename: Norman
authors.initials: N
authors.lastname: Leeds
authors.forename: Dennis
authors.initials: D
authors.lastname: Pietronigro
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D002330:Carmustine / Q000008:administration & dosage*; D000431:Ethanol; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D015552:Injections, Intralesional; D008279:Magnetic Resonance Imaging; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000601:surgery; D013238:Stereotaxic Techniques; D015996:Survival Rate
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000431:Ethanol; D002330:Carmustine