Bevacizumab and temozolomide versus temozolomide alone as neoadjuvant treatment in unresected glioblastoma: the GENOM 009 randomized phase II trial
Por:
Balana, C, De Las Penas, R, Sepulveda, JM, Gil-Gil, MJ, Luque, R, Gallego, O, Carrato, C, Sanz, C, Reynes, G, Herrero, A, Ramirez, JL, Perez-Segura, P, Berrocal, A, Vieitez, JM, Garcia, A, Vazquez-Estevez, S, Peralta, S, Fernandez, I, Henriquez, I, Martinez-Garcia, M, De la Cruz, JJ, Capellades, J, Giner, P, Villa, S
Publicada:
1 may 2016
Resumen:
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.
Filiaciones:
Balana, C:
Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Med Oncol Serv, Carretera Canyet S-N, Badalona 08916, Spain
De Las Penas, R:
Hosp Prov Castellon, Med Oncol Serv, Castellon de La Plana, Spain
Sepulveda, JM:
Univ Hosp, Med Oncol Serv, Octubre 12, Madrid, Spain
Gil-Gil, MJ:
Hosp Llobregat, IDIBELL, Inst Catala Oncol, Med Oncol Serv, Barcelona, Spain
Luque, R:
Hosp Univ Virgen Nieves, Med Oncol Serv, Granada, Spain
Gallego, O:
Hosp Santa Creu & Sant Pau, Med Oncol Serv, Barcelona, Spain
Carrato, C:
Hosp Badalona Germans Trias & Pujol, Pathol Serv, Badalona, Spain
Sanz, C:
Hosp Badalona Germans Trias & Pujol, Pathol Serv, Badalona, Spain
Reynes, G:
Hosp Univ La Fe, Med Oncol Serv, Valencia, Spain
Herrero, A:
Hosp Miguel Servet, Med Oncol Serv, Zaragoza, Spain
Ramirez, JL:
Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Lab Mol Canc Biol, Badalona, Spain
Perez-Segura, P:
Hosp Univ Clin San Carlos, Med Oncol Serv, Madrid, Spain
Berrocal, A:
Hosp Gen Univ Valencia, Med Oncol Serv, Valencia, Spain
Vieitez, JM:
Hosp Univ Cent Asturias, Med Oncol Serv, Oviedo, Spain
Garcia, A:
Hosp Marques Valdecilla, Med Oncol Serv, Santander, Spain
Vazquez-Estevez, S:
Hosp Univ Lucus Augusti, Med Oncol Serv, Lugo, Spain
Peralta, S:
Hosp St Joan Reus, Med Oncol Serv, Reus, Spain
Fernandez, I:
Hosp Xeral Cies, Med Oncol Serv, Vigo, Spain
Henriquez, I:
Hosp St Joan Reus, Radiat Oncol Serv, Reus, Spain
Martinez-Garcia, M:
Hosp Mar, Med Oncol Serv, Barcelona, Spain
De la Cruz, JJ:
Autonomous Univ Madrid, Sch Med, Dept Prevent Med & Publ Hlth, E-28049 Madrid, Spain
Capellades, J:
Hosp Mar, Serv Radiol, Barcelona, Spain
Giner, P:
Hosp Badalona Germans Trias & Pujol, Dept Pharm, Badalona, Spain
Villa, S:
Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Radiat Oncol Serv, Badalona, Spain
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