title: Gliadel wafer implantation combined with standard radiotherapy and concurrent followed by adjuvant temozolomide for treatment of newly diagnosed high-grade glioma: a systematic literature review.
abstract: Since 2003, only two chemotherapeutic agents, evaluated in phase III trials, have been approved by the US Food and Drug Administration for treatment of newly diagnosed high-grade glioma (HGG): Gliadel wafers (intracranially implanted local chemotherapy) and temozolomide (TMZ) (systemic chemotherapy). Neither agent is curative, but each has been shown to improve median overall survival (OS) compared to radiotherapy (RT) alone. To date, no phase III trial has tested these agents when used in sequential combination; however, a number of smaller trials have reported favorable results. We performed a systematic literature review to evaluate the combination of Gliadel wafers with standard RT (60 Gy) plus concurrent and adjuvant TMZ (RT/TMZ) for newly diagnosed HGG. A literature search was conducted for the period of January 1995 to September 2015. Data were extracted and categorized, and means and ranges were determined. A total of 11 publications met criteria, three prospective trials and eight retrospective studies, representing 411 patients who received Gliadel plus standard RT/TMZ. Patients were similar in age, gender, and performance status. The weighted mean of median OS was 18.2 months (ten trials, n = 379, range 12.7 to 21.3 months), and the weighted mean of median progression-free survival was 9.7 months (seven trials, n = 287, range 7 to 12.9 months). The most commonly reported grade 3 and 4 adverse events were myelosuppression (10.22 %), neurologic deficit (7.8 %), and healing abnormalities (4.3 %). Adverse events reflected the distinct independent safety profiles of Gliadel wafers and RT/TMZ, with little evidence of enhanced toxicity from their use in sequential combination. In the 11 identified trials, an increased benefit from sequentially combining Gliadel wafers with RT/TMZ was strongly suggested. Median OS tended to be improved by 3 to 4 months beyond that observed for Gliadel wafers or TMZ when used alone in the respective phase III trials. Larger prospective trials of Gliadel plus RT/TMZ are warranted.
authors.affiliation: Department of Neurology, Barrow Neurological Institute, 500 W. Thomas Rd, Suite 300, Phoenix, AZ, 85013, USA. lynn.ashby@dignityhealth.org.
authors.forename: Lynn S
authors.initials: LS
authors.lastname: Ashby
authors.affiliation: Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, 85013, USA.
authors.forename: Kris A
authors.initials: KA
authors.lastname: Smith
authors.affiliation: Department of Radiation Oncology, Arizona Cancer Center, University of Arizona, Tucson, AZ, 85724, USA.
authors.forename: Baldassarre
authors.initials: B
authors.lastname: Stea
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy / Q000379:methods; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003652:Decanoic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004343:Drug Implants; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D011091:Polyesters / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077204:Temozolomide; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003652:Decanoic Acids; D004343:Drug Implants; D011091:Polyesters; C574855:carmustine, poliferprosan 20 drug combination; D003606:Dacarbazine; D002330:Carmustine; D000077204:Temozolomide
keywords: Efficacy; Gliadel wafers; Glioblastoma multiforme (GBM); High-grade glioma (HGG); Radiotherapy (RT); Safety; Systematic review; Temozolomide (TMZ)