Hypertension as a biomarker in patients with recurrent glioblastoma treated with antiangiogenic drugs:  a single-center experience and a critical review of the literature.
Treatment with angiogenesis inhibitors is becoming a cornerstone of modern anticancer therapy. Hypertension (HTN) is a common adverse event during antiangiogenic treatment and might represent a cancer biomarker in patients with recurrent glioblastoma treated with angiogenesis inhibitors. In a retrospective study, we analyzed 53 patients with recurrent glioblastoma treated with antiangiogenic drugs. Thirty patients were treated with sorafenib and 23 patients were treated with bevacizumab. All patients underwent brain gadolinium-enhanced MRI assessments according to the Radiologic Assessment in Neuro-Oncology criteria every 2 months or when clinically indicated. Blood pressure was measured before and during the treatment. We investigated whether treatment-related HTN may be associated with outcome in patients treated with antiangiogenic drugs. After 2 months of treatment, 24 patients (45%) achieved disease control: stable disease (17 patients) or a partial response (seven patients). The median overall survival from the start of antiangiogenic treatment was 7.3 months [95% confidence interval (CI) 6.02-8.5]; the median progression-free survival (PFS) was 2.7 months (95% CI 1.5-3.5); and the 6-month PFS was 32%. Twenty patients (38%) developed grades 2-3 HTN within 2 months of treatment. A significant association was found between HTN and disease control rate, and HTN and 6-month PFS; no significant association was found between HTN and the median PFS. According to univariate and multivariate analyses, HTN was related to a longer survival from antiangiogenic drug administration: 9.8 versus 4.8 months (P=0.001; hazard ratio=3.5, 95% CI 1.6-7.6). Our data indicate that HTN may be an effective biomarker in patients with recurrent glioblastoma treated with antiangiogenic drugs; in particular, it may be associated with a favorable effect on disease control, 6-month PFS, and the median overall survival.
Departments of Medical Oncologyl, Venetian Oncology Institute - IRCCS, Padua, Italy. giuseppe.lombardi@ioveneto.it
Giuseppe
G
Lombardi
Fable
F
Zustovich
Patrizia
P
Farina
Pasquale
P
Fiduccia
Alessandro
A
Della Puppa
Valentina
V
Polo
Roberta
R
Bertorelle
Marina P
MP
Gardiman
Alberto
A
Banzato
Pietro
P
Ciccarino
Luca
L
Denaro
Vittorina
V
Zagonel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D000068258:Bevacizumab; D001794:Blood Pressure / Q000187:drug effects; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D000077157:Sorafenib; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D010671:Phenylurea Compounds; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib