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Effects of treatment with megestrol acetate on the insulin-like growth factor system: time and dose dependency
S I Helle1, S Lundgren, S Geisler
1Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Abstract:
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.
Insights
Megestrol acetate (MA) treatment significantly increases total insulin-like growth factor-I (IGF-I) and moderately increases free IGF-I in breast cancer patients. This suggests anabolic effects, not direct anti-tumor action via the IGF-system.
Area of Science:
- Endocrinology
- Oncology
- Pharmacology
Background:
- Megestrol acetate (MA) is used to treat breast cancer and cachexia.
- The insulin-like growth factor (IGF) system plays roles in cancer and metabolism.
- Understanding MA's effects on the IGF system is crucial for its clinical application.
Purpose of the Study:
- To investigate the time and dose-dependent effects of MA on IGF-I, free IGF-I, and IGFBP-3 in breast cancer patients.
- To explore the relationship between MA treatment and alterations in the IGF system.
Main Methods:
- Patients received MA at fixed (160 mg/day) or escalating doses (40-800 mg/day).
- Plasma levels of total IGF-I and free IGF-I were measured.
- IGF-binding protein 3 (IGFBP-3) functional status was assessed using Western ligand blotting (WLB).
Main Results:
- Total IGF-I levels increased significantly within days and up to 2.66-fold over months of MA treatment.
- Free IGF-I levels showed a smaller increase (1.23-2.15-fold).
- A dose-dependent increase in IGF-I was observed up to 120 mg MA daily, with increased intact IGFBP-3 potentially explaining the discrepancy.
Conclusions:
- MA treatment profoundly increases total IGF-I and moderately increases free IGF-I.
- These IGF-system changes may contribute to MA's anabolic effects in cachexia.
- The findings do not support a direct anti-tumor effect of MA through IGF-system modulation in breast cancer.