Paclitaxel chemotherapy and vascular toxicity as assessed by flow-mediated and nitrate-mediated vasodilatation.
BACKGROUND
Antitumor activity of paclitaxel is based on promotion of abnormal microtubule (MT) assembly but it is also considered to have significant pro-inflammatory and anti-angiogenic effects in vivo and thus may cause vascular dysfunction.


METHODS
We studied 27 women treated with paclitaxel-containing combinations for breast or ovarian cancer. The control group was represented by 10 women with carcinoma of the uterine cervix who received low doses of weekly cisplatin as radiation sensitizer. We measured endothelial-dependent flow-mediated dilatation (FMD) and nitrate-mediated dilatation (NMD) of the right brachial artery by ultrasonography, as well as levels of the inflammatory cytokines TNF-alpha and IL-6 before and after chemotherapy.


RESULTS
Patients who received paclitaxel and an anthracycline had the most marked reduction in both FMD (p=0.005) and NMD (p=0.027). A significant reduction in FMD was also observed in patients treated with weekly paclitaxel (p=0.045), whereas NMD was not affected (p=0.421). Although TNF-alpha and IL-6 levels were different among chemotherapy groups after treatment, no significant differences were observed between levels of both markers before and after chemotherapy.


CONCLUSIONS
Treatment with paclitaxel-containing combinations impairs endothelial function in vivo but endothelial function deterioration is not related to the serum levels of inflammation markers.
Vassilakopoulou
M
M
Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra Hospital, Athens, Greece.
Mountzios
G
G
Papamechael
C
C
Protogerou
A D
AD
Aznaouridis
K
K
Katsichti
P
P
Venetsanou
K
K
Dimopoulos
M-A
MA
Ikonomidis
I
I
Papadimitriou
C A
CA
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D001943:Breast Neoplasms / Q000188:drug therapy; D016022:Case-Control Studies; D002945:Cisplatin / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*
D018943:Anthracyclines; D000972:Antineoplastic Agents, Phytogenic; D015415:Biomarkers; D015850:Interleukin-6; D011838:Radiation-Sensitizing Agents; D014409:Tumor Necrosis Factor-alpha; D017239:Paclitaxel; D002945:Cisplatin