Effect of all-trans-retinoic acid on the hypercoagulable state of patients with breast cancer.
To evaluate whether all-trans-retinoic acid (ATRA) is able to modulate the hemostatic system in patients with solid tumors, we studied patients with locally advanced breast cancer who were enrolled in a Phase Ib study of ATRA +/- Tamoxifen (Tam). In this study, two groups of 15 patients/each were treated for 21 days before operation with ATRA at three doses (15, 45, or 75 mg/m(2)/day on alternate days) given alone (group 1) or in combination with Tam (group 2). One additional group received Tam alone. Plasma samples were evaluated for hypercoagulation markers (FVIIa, F1+2, TAT, D-dimer), fibrinolysis proteins (t-PA, PAI-1), and coagulation inhibitors (protein C, AT). At baseline, cancer patients had FVIIa, F1+2, TAT, and PAI-1 significantly greater than control subjects. During treatment, in the patients given ATRA alone, hypercoagulation markers appeared unmodified. Instead, subjects given Tam alone had a significant elevation of FVIIa, F1+2, and TAT versus baseline. However, in the ATRA + Tam groups, hypercoagulation markers were decreased compared with Tam alone. These results suggest that in selected conditions, pre-operative ATRA may modulate the hypercoagulable state of breast cancer patients.
Falanga
Anna
A
Department of Hematology, Ospedali Riuniti, Largo Barozzi, 14128 Bergamo, Italy. annafalanga@yahoo.com
Toma
S
S
Marchetti
M
M
Palumbo
R
R
Raffo
P
P
Consonni
R
R
Marziali
S
S
Dastoli
G
G
Barbui
T
T
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use; D019851:Thrombophilia / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000097:blood; D014212:Tretinoin / Q000008:administration & dosage / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D013629:Tamoxifen; D014212:Tretinoin; D010959:Tissue Plasminogen Activator