Effects of tamoxifen and octreotide LAR on the IGF-system compared with tamoxifen monotherapy.
The insulin-like growth factor (IGF)-system was evaluated in 150 breast cancer patients participating in a randomised phase III trial comparing octreotide pamoate and tamoxifen with tamoxifen+placebo. Alterations in the IGF-system in the two treatment arms and individual changes with respect to outcome were compared. Serum IGF-I and -II, free IGF-I, and insulin-like growth factor binding protein 1-3 (IGFBP1-3) were measured by radioimmmunoassay (RIA)/immunoradiometric assay (IRMA) and IGFBPs by Western ligand blots (WLB) before and during treatment. Combined treatment caused a higher increase in IGFBP-1 and larger suppression of total and free IGF-I, IGF-II, and IGFBP-3 (P<0.01 for all), but less suppression of IGFBP-2 (P<0.05) compared with tamoxifen monotherapy. An increase in IGFBP-2 25% was associated with decreased progression-free survival (PFS) in the total patient population and combined treatment group. Similar response rates and time to progression in the treatment arms suggests moderate suppression of circulating IGF-I has no influence on clinical outcome.
Helle
S I
SI
Department of Medicine, Section of Oncology, Haukeland University Hospital, N-5021 Bergen, Norway.
Mietlowski
W
W
Guastalla
J P
JP
Szakolczai
I
I
Bajetta
E
E
Sommer
H
H
Baltali
E
E
Pinter
T
T
Csepreghy
M
M
Ottestad
L
L
Boni
C
C
Bryce
C
C
Klijn
J G M
JG
Lønning
P E
PE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000187:drug effects*; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage; D016016:Proportional Hazards Models; D013002:Somatomedins / Q000032:analysis / Q000187:drug effects*; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D013629:Tamoxifen; D015282:Octreotide