title: Clinical benefit in recurrent glioblastoma from adjuvant NovoTTF-100A and TCCC after temozolomide and bevacizumab failure: a preliminary observation.
abstract: The NovoTTF-100A is a device that emits alternating electric fields and it is approved for the treatment of recurrent glioblastoma. It works by perturbing tumor cells during mitosis as they enter anaphase leading to aneuploidy, asymmetric chromosome segregation and cell death with evidence of increased immunogenicity. Clinical trial data have shown equivalent efficacy when compared to salvage chemotherapies in recurrent disease. Responders were found to have had a lower dexamethasone usage and a higher rate of prior low-grade histology. We treated a series of patients with NovoTTF-100A and bevacizumab alone (n = 34) or in combination with a regimen consisting of 6-thioguanine, lomustine, capecitabine, and celecoxib (TCCC) (n = 3). Compared to the former cohort, the latter cohort exhibited a trend for prolonged overall survival, median 4.1 (0.3-22.7) months versus 10.3 (7.7-13.6) months respectively (P = 0.0951), with one experiencing an objective response with a 50% reduction in tumor size on magnetic resonance imaging despite possessing a larger tumor size at baseline and more severe neurologic dysfunction than the median for either group. These observations illustrate the possibility of improving survival and achieving a response in patients with end-stage recurrent glioblastoma by biasing the tumor toward anti-tumor immunologic response with a combination of NovoTTF-100A and TCCC, as well as the continuation of bevacizumab in order to limit dexamethasone use due to its global immunosuppressive effect on the patient.
authors.affiliation: Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wong
authors.forename: Edwin
authors.initials: E
authors.lastname: Lok
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Swanson
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D000069287:Capecitabine / Q000008:administration & dosage; D000068579:Celecoxib / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004599:Electric Stimulation Therapy; D005260:Female; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D000077204:Temozolomide; D013866:Thioguanine / Q000008:administration & dosage; D017211:Treatment Failure
chemical_list: D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D000068258:Bevacizumab; D000069287:Capecitabine; D008130:Lomustine; D003606:Dacarbazine; D013866:Thioguanine; D000068579:Celecoxib; D000077204:Temozolomide
keywords: Bevacizumab; NovoTTF-100A; chemotherapy; glioblastoma