Abstract
Background: The synthetic retinoid fenretinide (N-(4-hydroxyphenyl) retinamide, 4-HPR) has shown promising anticancer activity in preclinical studies, but its limited oral bioavailability has hindered clinical assessment. A novel lipid matrix, Lym-X-Sorb (LXS), was evaluated to improve fenretinide bioavailability and attain higher plasma concentrations. Patients and Methods: Adults with refractory malignancies were administered fenretinide/LXS oral powder in 2 divided doses over 24 h for 7 consecutive days every 21 days in a standard phase I dose-escalation study with pharmacokinetic analysis. Results: The principal toxicities observed were diarrhea, reversible night blindness, and allergic reaction. The maximum tolerated dose regimens were 1,000 mg/m 2/day divided into 2 daily doses for 7 days, every 21 days, and 800 mg/m 2/day divided into 3 daily doses for 7 consecutive days, every 21 days. Conclusion: Better fenretinide formulations are needed to improve adult patient acceptability and compliance and to achieve the consistent systemic exposures associated with activity in preclinical models.
Original language | English (US) |
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Pages (from-to) | 961-966 |
Number of pages | 6 |
Journal | Anticancer research |
Volume | 31 |
Issue number | 3 |
State | Published - Mar 2011 |
Externally published | Yes |
Keywords
- Clinical trial
- Fenretinide
- LXS oral powder
- Phase I
ASJC Scopus subject areas
- Oncology
- Cancer Research