Time course of fenretinide-induced modulation of circulating insulin-like growth factor (IGF)-I, IGF-II and IGFBP-3 in a bladder cancer chemoprevention trial

Rosalba Torrisi, Maura Mezzetti, Harriet Johansson, Antonina Barreca, Francesca Pigatto, Chris Robertson, Andrea Decensi

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Abstract

The insulin-like growth factor (IGF) system is widely involved in human carcinogenesis. A significant association between high circulating IGF-I concentrations and an increased risk of lung, colon, prostate and pre-menopausal breast cancer has recently been reported. Lowering plasma IGF-I may thus represent an attractive strategy to be pursued for chemopreventive purposes. We have previously shown that the synthetic retinoid fenretinide (4-HPR) lowers plasma IGF-I in pre-menopausal breast cancer patients. We investigated the effect of fenretinide on circulating IGF-I, IGF-II and IGFBP-3 measured at yearly intervals during the 2-year treatment period and one year after treatment discontinuation in a predominantly male population of patients with superficial bladder cancer. Repeated measures analysis, after adjustment for age, body mass index (BMI) and year of study, showed a significant effect of fenretinide on IGF-I levels, which were further lowered after the second year of treatment and only partially recovered after drug discontinuation. Differently from breast cancer patients, the effect of fenretinide was not modified by age. No significant effect was evident on IGFBP-3, IGF-II and the IGF-I+IGF-II/IGFBP-3 molar ratio, expressing the tissue availability of the mitogenic peptides, although IGF-II and the molar ratio were lowered by treatment by an overall mean of 16% and 15%, respectively. Given the increasingly recognized importance of circulating IGFs in the pathogenesis of different solid tumors, our findings strengthen the rationale for studying fenretinide as a chemopreventive agent. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)601-605
Number of pages5
JournalInternational Journal of Cancer
Volume87
Issue number4
DOIs
Publication statusPublished - 2000

Fingerprint

Fenretinide
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor II
Chemoprevention
Insulin-Like Growth Factor I
Urinary Bladder Neoplasms
Breast Neoplasms
Retinoids
Somatomedins
Therapeutics
Prostate
Colon
Carcinogenesis
Body Mass Index
Lung
Peptides
Pharmaceutical Preparations
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Time course of fenretinide-induced modulation of circulating insulin-like growth factor (IGF)-I, IGF-II and IGFBP-3 in a bladder cancer chemoprevention trial. / Torrisi, Rosalba; Mezzetti, Maura; Johansson, Harriet; Barreca, Antonina; Pigatto, Francesca; Robertson, Chris; Decensi, Andrea.

In: International Journal of Cancer, Vol. 87, No. 4, 2000, p. 601-605.

Research output: Contribution to journalArticle

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