Effects of treatment with megestrol acetate on the insulin-like growth factor system: time and dose dependency

This study was designed to evaluate time and dose dependency of alterations in insulin-like growth factor (IGF)-I, free IGF-I and the functional status of IGF-binding protein (IGFBP)-3 in breast cancer patients during treatment with megestrol acetate (MA). In 16 patients receiving MA 160 mg daily, t...

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Bibliographic Details
Published in:European journal of cancer (1990) 1999-07, Vol.35 (7), p.1070-1075
Main Authors: Helle, S.I, Lundgren, S, Geisler, S, Ekse, D, Holly, J.M.P, Lønning, P.E
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Antineoplastic agents
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Blotting, Western
breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - metabolism
Chemotherapy
Dose-Response Relationship, Drug
endocrine effects
Female
Humans
Insulin-Like Growth Factor Binding Proteins - metabolism
Insulin-Like Growth Factor I - metabolism
Medical sciences
Megestrol Acetate - therapeutic use
Middle Aged
Pharmacology. Drug treatments
Postmenopause
progestin
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Summary:This study was designed to evaluate time and dose dependency of alterations in insulin-like growth factor (IGF)-I, free IGF-I and the functional status of IGF-binding protein (IGFBP)-3 in breast cancer patients during treatment with megestrol acetate (MA). In 16 patients receiving MA 160 mg daily, total IGF-I levels increased gradually (significant after 3 days on treatment) by a maximum of 2.66-fold after 5–6 months on treatment. However, free (readily dissociable) IGF-I levels increased to a smaller extent (1.23–2.15-fold). This discrepancy may be due to an increase in intact IGFBP-3 determined by Western ligand blotting (WLB). Similar findings were observed in 12 patients treated with MA in escalating doses from 40–800 mg daily. A dose-dependent increase in IGF-I was observed up to a dose level of 120 mg daily. We conclude that treatment with MA caused a profound increase in plasma levels of total IGF-I accompanied by a moderate increase in free IGF-I. This may explain the anabolic effects of MA in patients suffering from cachexia, but refute the hypothesis that alterations in the IGF-system may contribute to the antitumour effects of MA in breast cancer patients.
ISSN:0959-8049
1879-0852
DOI:10.1016/S0959-8049(99)00055-6