Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: a Hellenic Cooperative Oncology Group (HeCOG) study.
It is well known that low-dose metronomic chemotherapy has antiangiogenic             activity. The aim of the present trial was to investigate the antiangiogenic properties             of weekly docetaxel in patients with metastatic breast cancer. In total, 157 metastatic             breast cancer patients received 35 mg/m2 docetaxel weekly as a recommended treatment.             Blood samples were collected before the start of chemotherapy (baseline) and during             treatment. Nitric oxide (NO) and vascular endothelial growth factor A (VEGF-A)             plasma levels were measured at baseline and during treatment, while VEGF-A, endothelial             nitric oxide synthase (eNOS) and thrombospondin-1 (THBS-1) peripheral blood mRNA             levels were measured at baseline, in 127 patients and 39 female healthy controls.             In general, the treatment was well-tolerated. Sixty-one patients (38%) achieved             an objective response (4% complete and 34% partial response), while 52 (33%) had             stable disease and 27 (17%) progressed. At a median follow-up of 33.5 months (range             2.8-45.0), 118 patients (74%) demonstrated disease progression and 94 (59%) had             died. Median progression-free survival (PFS) was 8.8 months and median overall             survival (OS) was 27.7 months. Median baseline level of plasma NO was significantly             lower in patients than in healthy controls (p=0.010), while none of the plasma             markers significantly changed upon docetaxel treatment. In addition, the median             relative quantification value for THBS-1 mRNA was significantly higher (p<0.001)             in patients as compared to healthy controls. NO plasma levels were positively             associated with the number of organs involved (p=0.008). In multivariate analysis,             low eNOS mRNA levels showed adverse prognostic significance for OS and high THBS-1             mRNA levels were found to be associated with shorter OS and PFS, independently             from established clinical prognostic factors. Although an antiangiogenic activity             of weekly docetaxel was not demonstrated in the present study, some interesting             observations regarding the prognostic role of a number of blood angiogenic markers             could be made.
Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, University of Athens School of Medicine, Athens, Greece. pectasid@otenet.gr
Dimitrios
D
Pectasides
George
G
Papaxoinis
Vassiliki
V
Kotoula
Helen
H
Fountzilas
Ippokratis
I
Korantzis
Angelos
A
Koutras
Athanasios M
AM
Dimopoulos
Pavlos
P
Papakostas
Gerasimos
G
Aravantinos
Ioannis
I
Varthalitis
Paris
P
Kosmidis
Dimosthenis
D
Skarlos
Evangelos
E
Bournakis
Dimitrios
D
Bafaloukos
Haralabos P
HP
Kalofonos
Konstantine T
KT
Kalogeras
George
G
Fountzilas
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D000077143:Docetaxel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood*; D009569:Nitric Oxide / Q000097:blood; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids / Q000627:therapeutic use*; D019700:Thrombospondin 1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D043823:Taxoids; D019700:Thrombospondin 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077143:Docetaxel; D009569:Nitric Oxide