title: Neoadjuvant cisplatin plus temozolomide versus standard treatment in patients with unresectable glioblastoma or anaplastic astrocytoma: a differential effect of MGMT methylation.
abstract: Patients with unresectable glioblastoma or anaplastic astrocytoma have a dismal prognosis. The role of neoadjuvant chemotherapy prior to irradiation in these patients has been studied primarily in non-randomized studies. We have compared the effect of neoadjuvant chemotherapy plus radiotherapy versus concomitant radiotherapy plus temozolomide in a retrospective analysis of two consecutive series of patients in whom surgery consisted of biopsy only. From 2003 to 2005, 23 patients received two cycles of temozolomide plus cisplatin followed by radiotherapy (Cohort 1), and from 2006 to 2010, 23 additional patients received concomitant radiotherapy and temozolomide followed by adjuvant temozolomide (Cohort 2). In Cohort 1, 91.3 % of patients received all planned chemotherapy cycles. Progression-free and overall survival were 3.3 and 8.5 months, respectively. In Cohort 2, progression-free and overall survival were 5.1 and 11.2 months, respectively. No differences between the two groups were observed in rate of completion of radiotherapy, progression-free or overall survival. MGMT methylation was assessed in 91.3 % of patients. In Cohort 1, patients without MGMT methylation showed a trend towards shorter progression-free survival (P = 0.09), while in Cohort 2, patients without MGMT methylation had longer progression-free survival (P = 0.04). In the overall patient population, neoadjuvant temozolomide plus cisplatin had neither a positive nor negative influence on outcome. However, our findings indicate that patients with methylated MGMT may derive greater benefit from neoadjuvant temozolomide than those with unmethylated MGMT.
authors.affiliation: Medical Oncology, Catalan Institute of Oncology (ICO), University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Capdevila
authors.forename: Sara
authors.initials: S
authors.lastname: Cros
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Ramirez
authors.forename: Carolina
authors.initials: C
authors.lastname: Sanz
authors.forename: Cristina
authors.initials: C
authors.lastname: Carrato
authors.forename: Margarita
authors.initials: M
authors.lastname: Romeo
authors.forename: Olatz
authors.initials: O
authors.lastname: Etxaniz
authors.forename: Cristina
authors.initials: C
authors.lastname: Hostalot
authors.forename: Ana
authors.initials: A
authors.lastname: Massuet
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Cuadra
authors.forename: Salvador
authors.initials: S
authors.lastname: Villà
authors.forename: Carmen
authors.initials: C
authors.lastname: Balañà
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D001254:Astrocytoma / Q000378:metabolism / Q000628:therapy*; D001932:Brain Neoplasms / Q000378:metabolism / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000628:therapy; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D011838:Radiation-Sensitizing Agents; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D002945:Cisplatin; D000077204:Temozolomide