Influence of bicalutamide with or without tamoxifen or anastrozole on insulin-like growth factor 1 and binding proteins in prostate cancer patients.
BACKGROUND
There is growing evidence that IGF-1 and binding proteins may be involved in prostate cancer promotion and progression.


METHODS
IGF-1 and binding proteins (IGFBP-1 and 3) serum levels were measured at baseline and after 3 and 6 months of treatment in a selected group of patients with prostate cancer who were randomly assigned to treatment with bicalutamide, bicalutamide plus anastrozole or bicalutamide plus tamoxifen in a comparative study investigating the role of pharmacological medication in the development of bicalutamide-induced gynecomastia.


RESULTS
Bicalutamide monotherapy does not appear to alter the IGF-1/IGFBP system. In fact, the increase in IGF-1 levels induced by this treatment was paralleled by comparable increases in binding protein (IGFBP-3). No major changes from baseline up to month 6 either in IGF-1 or in IGFBP-1 and 3 were observed in the bicalutamide plus anastrozole arm. The addition of tamoxifen to bicalutamide produced a sharp decrease in IGF-1 levels (p<0.001) coupled with an increase in both IGFBP-1 (p=0.001) and, to a lesser extent, IGFBP-3 (p=0.5).


CONCLUSIONS
The concurrent administration of tamoxifen and bicalutamide reduces the synthesis and bioavailability of IGF-1. Moreover, increased binding protein levels might exert antiproliferative and proapoptotic effects on prostate cancer cells, independently of the IGF-1/IGF receptor-mediated survival system. Both effects might have a synergistic inhibitory influence on prostate cancer growth.
Boccardo
F
F
Department of Medical Oncology, National Cancer Research Institute and University of Genoa, Italy. f.boccardo@unige.it
Rubagotti
A
A
Battaglia
M
M
Zattoni
F
F
Bertaccini
A
A
Romagnoli
A
A
Conti
G
G
D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000813:Anilides / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000096:biosynthesis; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D013629:Tamoxifen / Q000008:administration & dosage*; D014105:Tosyl Compounds; D014230:Triazoles / Q000008:administration & dosage*
D000813:Anilides; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D009570:Nitriles; D014105:Tosyl Compounds; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole; D007334:Insulin-Like Growth Factor I; C053541:bicalutamide