title: Bevacizumab and temozolomide versus temozolomide alone as neoadjuvant treatment in unresected glioblastoma: the GENOM 009 randomized phase II trial.
abstract: We sought to determine the impact of bevacizumab on reduction of tumor size prior to chemoradiotherapy in unresected glioblastoma patients. Patients were randomized 1:1 to receive temozolomide (TMZ arm) or temozolomide plus bevacizumab (TMZ + BEV arm). In both arms, neoadjuvant treatment was temozolomide (85 mg/m(2), days 1-21, two 28-day cycles), concurrent radiation plus temozolomide, and six cycles of adjuvant temozolomide. In the TMZ + BEV arm, bevacizumab (10 mg/kg) was added on days 1 and 15 of each neoadjuvant cycle and on days 1, 15 and 30 of concurrent treatment. The primary endpoint was investigator-assessed response to neoadjuvant treatment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the impact on outcome of MGMT methylation in tumor and serum. One hundred and two patients were included; 43 in the TMZ arm and 44 in the TMZ + BEV arm were evaluable for response. Results favored the TMZ + BEV arm in terms of objective response (3 [6.7 %] vs. 11 [22.9 %]; odds ratio 4.2; P = 0.04). PFS and OS were longer in the TMZ + BEV arm, though the difference did not reach statistical significance. MGMT methylation in tumor, but not in serum, was associated with outcome. More patients experienced toxicities in the TMZ + BEV than in the TMZ arm (P = 0.06). The combination of bevacizumab plus temozolomide is more active than temozolomide alone and may well confer benefit in terms of tumor shrinkage in unresected patients albeit at the expense of greater toxicity.
authors: Medical Oncology Service, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Carretera Canyet, s/n, 08916, Badalona, Spain. cbalana@iconcologia.net.
authors: Carmen
authors: C
authors: Balana
authors: Medical Oncology Service, Hospital Provincial de Castellón, Castellón, Spain.
authors: Ramon
authors: R
authors: De Las Penas
authors: Medical Oncology Service, Hospital Universitario, 12 de Octubre, Madrid, Spain.
authors: Juan Manuel
authors: JM
authors: Sepúlveda
authors: Medical Oncology Service, Institut Català d'Oncologia-IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
authors: Miguel J
authors: MJ
authors: Gil-Gil
authors: Medical Oncology Service, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors: Raquel
authors: R
authors: Luque
authors: Medical Oncology Service, Hospital de Sant Pau, Barcelona, Spain.
authors: Oscar
authors: O
authors: Gallego
authors: Pathology Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors: Cristina
authors: C
authors: Carrato
authors: Pathology Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors: Carolina
authors: C
authors: Sanz
authors: Medical Oncology Service, Hospital Universitario La Fe, Valencia, Spain.
authors: Gaspar
authors: G
authors: Reynes
authors: Medical Oncology Service, Hospital Miguel Servet, Zaragoza, Spain.
authors: Ana
authors: A
authors: Herrero
authors: Cancer Molecular Biology Laboratory, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors: Jose Luis
authors: JL
authors: Ramirez
authors: Medical Oncology Service, Hospital Universitario Clínico San Carlos, Madrid, Spain.
authors: Pedro
authors: P
authors: Pérez-Segura
authors: Medical Oncology Service, Hospital General Universitario de Valencia, Valencia, Spain.
authors: Alfonso
authors: A
authors: Berrocal
authors: Medical Oncology Service, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors: Jose Maria
authors: JM
authors: Vieitez
authors: Medical Oncology Service, Hospital Marqués de Valdecilla, Santander, Spain.
authors: Almudena
authors: A
authors: Garcia
authors: Medical Oncology Service, Hospital Universitario Lucus Augusti, Lugo, Spain.
authors: Sergio
authors: S
authors: Vazquez-Estevez
authors: Medical Oncology Service, Hospital Sant Joan de Reus, Reus, Spain.
authors: Sergi
authors: S
authors: Peralta
authors: Medical Oncology Service, Hospital Xeral-Cies, Vigo, Spain.
authors: Isaura
authors: I
authors: Fernandez
authors: Radiation Oncology Service, Hospital Sant Joan de Reus, Reus, Spain.
authors: Ivan
authors: I
authors: Henriquez
authors: Medical Oncology Service, Hospital del Mar, Barcelona, Spain.
authors: Maria
authors: M
authors: Martinez-Garcia
authors: Department of Preventive Medicine and Public Health, School of Medicine, Autonomous University of Madrid, Madrid, Spain.
authors: Juan Jose
authors: JJ
authors: De la Cruz
authors: Radiology Service, Hospital del Mar, Barcelona, Spain.
authors: Jaume
authors: J
authors: Capellades
authors: Pharmacy Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors: Pilar
authors: P
authors: Giner
authors: Radiation Oncology Service, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors: Salvador
authors: S
authors: Villà
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D000077204:Temozolomide
chemical_list: D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Bevacizumab; Glioblastoma; MGMT; Neoadjuvant; Serum MGMT; Temozolomide