TY - JOUR
T1 - Five-year administration of fenretinide
T2 - Pharmacokinetics and effects on plasma retinol concentrations
AU - Formelli, Franca
AU - Clerici, Monica
AU - Campa, Tiziana
AU - Mauro, Maria Gaetana Di
AU - Magni, Andrea
AU - Mascotti, Gustavo
AU - Moglia, Daniele
AU - De Palo, Giuseppe
AU - Costa, Alberto
AU - Veronesi, Umberto
PY - 1993
Y1 - 1993
N2 - Purpose: Monitoring of fenretinide (4HPR) levels, kinetics, and effects on retinal was performed in patients who participated in a phase I trial and who continued to be treated for 5 years as phase III trial patients. Accumulation of 4HPR in the breast was also assessed. Patients and Methods: Plasma concentrations of 4HPR, of its main metabolite N-(4-methoxyphenyl)retinamide (4MPR), and of retinal were assayed by high-performance liquid chromatography (HPLC) in breast cancer patients treated orally with 4HPR 200 mg/d for 5 years with a 3-day drug interruption at the end of each month. Results: 4HPR, at 200 mg/d, resulted in average 4HPR plasma levels of approximately 1 μmol/L, which remained steady and caused steady retinal level reduction; 4MPR levels, similar to those of 4HPR, slightly but significantly increased during the first 35 months, but at 5 years they were similar to those at 5 months. During daily treatment, baseline retinal concentrations were reduced by 71 %; after a 3-day drug interruption, all pa-tients recovered and the mean reduction was 38%. After discontinuation of 5-year treatment, 4HPR and 4MPR half-lives (t1/2 β) were 27 and 54 hours, respectively, similar to those reported after 28 daily treatments. After 6 and 1 2 months, the concentrations of 4HPR were at the limit of detectability (0.01 μmol/L), whereas those of 4MPR were five times higher. Baseline retinal concentrations were already recovered after 1 month. Accumulation of this retinoid in the breast was evidenced by concentrations of 4HPR and 4MPR in nipple discharge and in breast biopsies that were 10 and 20 times higher, respectively, than those found in plasma. Conclusion: 4HPR, at 200 mg/d for 5 years, resulted in constant drug plasma levels and constant retinal level reduction. After treatment interruption, 4HPR plasma concentrations decreased at the limit of detectability at 6 months and baseline retinal plasma concentrations were recovered after 1 month.
AB - Purpose: Monitoring of fenretinide (4HPR) levels, kinetics, and effects on retinal was performed in patients who participated in a phase I trial and who continued to be treated for 5 years as phase III trial patients. Accumulation of 4HPR in the breast was also assessed. Patients and Methods: Plasma concentrations of 4HPR, of its main metabolite N-(4-methoxyphenyl)retinamide (4MPR), and of retinal were assayed by high-performance liquid chromatography (HPLC) in breast cancer patients treated orally with 4HPR 200 mg/d for 5 years with a 3-day drug interruption at the end of each month. Results: 4HPR, at 200 mg/d, resulted in average 4HPR plasma levels of approximately 1 μmol/L, which remained steady and caused steady retinal level reduction; 4MPR levels, similar to those of 4HPR, slightly but significantly increased during the first 35 months, but at 5 years they were similar to those at 5 months. During daily treatment, baseline retinal concentrations were reduced by 71 %; after a 3-day drug interruption, all pa-tients recovered and the mean reduction was 38%. After discontinuation of 5-year treatment, 4HPR and 4MPR half-lives (t1/2 β) were 27 and 54 hours, respectively, similar to those reported after 28 daily treatments. After 6 and 1 2 months, the concentrations of 4HPR were at the limit of detectability (0.01 μmol/L), whereas those of 4MPR were five times higher. Baseline retinal concentrations were already recovered after 1 month. Accumulation of this retinoid in the breast was evidenced by concentrations of 4HPR and 4MPR in nipple discharge and in breast biopsies that were 10 and 20 times higher, respectively, than those found in plasma. Conclusion: 4HPR, at 200 mg/d for 5 years, resulted in constant drug plasma levels and constant retinal level reduction. After treatment interruption, 4HPR plasma concentrations decreased at the limit of detectability at 6 months and baseline retinal plasma concentrations were recovered after 1 month.
UR - http://www.scopus.com/inward/record.url?scp=0027360292&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027360292&partnerID=8YFLogxK
M3 - Article
C2 - 8410127
AN - SCOPUS:0027360292
VL - 11
SP - 2036
EP - 2042
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 10
ER -