Bevacizumab versus alkylating chemotherapy in recurrent glioblastoma
Standard
Bevacizumab versus alkylating chemotherapy in recurrent glioblastoma. / Seystahl, Katharina; Hentschel, Bettina; Loew, Sarah; Gramatzki, Dorothee; Felsberg, Jörg; Herrlinger, Ulrich; Westphal, Manfred; Schackert, Gabriele; Thon, Niklas; Tatagiba, Marcos; Pietsch, Torsten; Reifenberger, Guido; Löffler, Markus; Wick, Wolfgang; Weller, Michael; German Glioma Network.
in: J CANCER RES CLIN, Jahrgang 146, Nr. 3, 03.2020, S. 659-670.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Bevacizumab versus alkylating chemotherapy in recurrent glioblastoma
AU - Seystahl, Katharina
AU - Hentschel, Bettina
AU - Loew, Sarah
AU - Gramatzki, Dorothee
AU - Felsberg, Jörg
AU - Herrlinger, Ulrich
AU - Westphal, Manfred
AU - Schackert, Gabriele
AU - Thon, Niklas
AU - Tatagiba, Marcos
AU - Pietsch, Torsten
AU - Reifenberger, Guido
AU - Löffler, Markus
AU - Wick, Wolfgang
AU - Weller, Michael
AU - German Glioma Network
PY - 2020/3
Y1 - 2020/3
N2 - BACKGROUND: The use of alkylating chemotherapy versus bevacizumab for recurrent glioblastoma remains controversial. Here, we tested the hypothesis that the activity of alkylators, but not that of bevacizumab, would be associated with the O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status.METHODS: We analyzed a cohort of patients treated at centers of the German Glioma Network or the University Hospital Zurich with alkylating agent-based chemotherapy (n = 260) or bevacizumab without or with irinotecan (n = 84) for first recurrence of glioblastoma. Outcome was stratified for O6-methylguanine DNA methyltransferase (MGMT) status and crossover to bevacizumab or alkylators at further progression.RESULTS: Median post-recurrence survival-1 (PRS-1) for patients receiving alkylating agents at first recurrence was longer than with bevacizumab (11.1 versus 7.4 months, p < 0.001). The use of alkylators was associated with longer PRS-1 for patients with a methylated versus unmethylated MGMT promoter (p = 0.017). For patients receiving bevacizumab, PRS-1 was not different with or without MGMT promoter methylation. PRS-1 was longer in patients receiving alkylating chemotherapy compared to bevacizumab for patients with methylated (p < 0.001) or unmethylated MGMT promoter (p = 0.034). For patients with alkylators at first recurrence receiving bevacizumab at any further recurrence, PRS-1 was longer than in patients receiving bevacizumab first and alkylators thereafter (p = 0.002).CONCLUSIONS: This study confirms limited value of bevacizumab in recurrent glioblastoma independent of MGMT status. Alkylating agents have activity in recurrent glioblastoma, especially in the context of MGMT promoter methylation.
AB - BACKGROUND: The use of alkylating chemotherapy versus bevacizumab for recurrent glioblastoma remains controversial. Here, we tested the hypothesis that the activity of alkylators, but not that of bevacizumab, would be associated with the O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status.METHODS: We analyzed a cohort of patients treated at centers of the German Glioma Network or the University Hospital Zurich with alkylating agent-based chemotherapy (n = 260) or bevacizumab without or with irinotecan (n = 84) for first recurrence of glioblastoma. Outcome was stratified for O6-methylguanine DNA methyltransferase (MGMT) status and crossover to bevacizumab or alkylators at further progression.RESULTS: Median post-recurrence survival-1 (PRS-1) for patients receiving alkylating agents at first recurrence was longer than with bevacizumab (11.1 versus 7.4 months, p < 0.001). The use of alkylators was associated with longer PRS-1 for patients with a methylated versus unmethylated MGMT promoter (p = 0.017). For patients receiving bevacizumab, PRS-1 was not different with or without MGMT promoter methylation. PRS-1 was longer in patients receiving alkylating chemotherapy compared to bevacizumab for patients with methylated (p < 0.001) or unmethylated MGMT promoter (p = 0.034). For patients with alkylators at first recurrence receiving bevacizumab at any further recurrence, PRS-1 was longer than in patients receiving bevacizumab first and alkylators thereafter (p = 0.002).CONCLUSIONS: This study confirms limited value of bevacizumab in recurrent glioblastoma independent of MGMT status. Alkylating agents have activity in recurrent glioblastoma, especially in the context of MGMT promoter methylation.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antineoplastic Agents, Alkylating/therapeutic use
KW - Antineoplastic Agents, Immunological/therapeutic use
KW - Bevacizumab/therapeutic use
KW - Brain Neoplasms/drug therapy
KW - DNA Methylation/genetics
KW - DNA Modification Methylases/genetics
KW - DNA Repair Enzymes/genetics
KW - Female
KW - Glioblastoma/drug therapy
KW - Humans
KW - Male
KW - Middle Aged
KW - Neoplasm Recurrence, Local/drug therapy
KW - Progression-Free Survival
KW - Promoter Regions, Genetic/genetics
KW - Retrospective Studies
KW - Tumor Suppressor Proteins/genetics
KW - Young Adult
U2 - 10.1007/s00432-019-03086-9
DO - 10.1007/s00432-019-03086-9
M3 - SCORING: Journal article
C2 - 31754832
VL - 146
SP - 659
EP - 670
JO - J CANCER RES CLIN
JF - J CANCER RES CLIN
SN - 0171-5216
IS - 3
ER -
