{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:50:45Z","timestamp":1783633845340,"version":"3.55.0"},"reference-count":44,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2000,1,1]]},"abstract":"<jats:p>PURPOSE: N-(4-hydroxyphenyl) retinamide ([4-HPR], Fenretinide; R.W. Johnson Pharmaceutical Research Institute, Springhouse, PA) and tamoxifen (TAM) have synergistic antitumor and chemopreventive activity against mammary cancer in preclinical studies. We performed a pilot study of this combination in women at high risk for developing breast cancer.<\/jats:p><jats:p>PATIENTS AND METHODS: Thirty-two women were treated with four cycles of 4-HPR, 200 mg orally (PO) for 25 days of each 28-day cycle, and TAM, 20 mg PO once daily for 23 months beginning after 1 month of 4-HPR alone. Tolerability, dark adaptometry, tissue biopsies, and retinoid plasma concentrations (Cp) were evaluated.<\/jats:p><jats:p>RESULTS: Symptomatic reversible nyctalopia developed in two patients (6%) on 4-HPR, but 16 (73%) of 22 patients had reversible changes in dark adaptation, which correlated with relative decrease in Cp retinol (P \u2264 .01). Four patients stopped treatment for side effects, and 84% of patients had hot flashes. Other commonly reported (grade \u2264 2) reversible toxicities included skin and ocular dryness, fatigue, and mood changes. Serum high-density lipoprotein increased and cholesterol decreased from baseline to month 4. Baseline mean \u00b1 SD Cp retinol was 708 \u00b1 280 ng\/mL. Mean \u00b1 SD Cp of 4-HPR, N-(4-methoxyphenyl) retinamide (4-MPR), and retinol after 1 month of 4-HPR were 0.34 \u00b1 0.21 \u03bcmol\/L, 0.28 \u00b1 0.21 \u03bcmol\/L, and 282 \u00b1 127 ng\/mL, respectively. Mean retinoid Cps did not change after 3 months of 4-HPR + TAM.<\/jats:p><jats:p>CONCLUSIONS: TAM administration did not affect Cp 4-HPR or 4-MPR. Reversible nyctalopia correlated with relative decrease in Cp retinol but was not symptomatic for most patients. TAM + 4-HPR has acceptable tolerability for this high-risk cohort.<\/jats:p>","DOI":"10.1200\/jco.2000.18.2.275","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T09:32:46Z","timestamp":1487928766000},"page":"275-275","source":"Crossref","is-referenced-by-count":58,"title":["Pilot Trial of the Safety, Tolerability, and Retinoid Levels of N-(4-hydroxyphenyl) Retinamide in Combination With Tamoxifen in Patients at High Risk for Developing Invasive Breast Cancer"],"prefix":"10.1200","volume":"18","author":[{"given":"Barbara","family":"Conley","sequence":"first","affiliation":[{"name":"From the Greenebaum Cancer CenterDivisions of Hematology and Oncology, and Department of Medicine, University of Maryland School of Medicine, Baltimore; Medicine Branch, Laboratory of Pathology, and Surgery Branch, Division of Clinical Sciences, National Cancer Institute (NCI); Pharmacy Department, Department of Radiology, Warren Grant Magnusen Clinical Center; and National Eye Institute, National Institutes of Health, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"O\u2019Shaughnessy","sequence":"additional","affiliation":[{"name":"From the Greenebaum Cancer CenterDivisions of Hematology and Oncology, and Department of Medicine, University of Maryland School of Medicine, Baltimore; Medicine Branch, Laboratory of Pathology, and Surgery Branch, Division of Clinical Sciences, National Cancer Institute (NCI); Pharmacy Department, Department of Radiology, Warren Grant Magnusen Clinical Center; and National Eye Institute, National Institutes of Health, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Prindiville","sequence":"additional","affiliation":[{"name":"From the Greenebaum Cancer CenterDivisions of Hematology and Oncology, and Department of Medicine, University of Maryland School of Medicine, Baltimore; Medicine Branch, Laboratory of Pathology, and Surgery Branch, Division of Clinical Sciences, National Cancer Institute (NCI); Pharmacy Department, Department of Radiology, Warren Grant Magnusen Clinical Center; and National Eye Institute, National Institutes of Health, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Lawrence","sequence":"additional","affiliation":[{"name":"From the Greenebaum Cancer CenterDivisions of Hematology and Oncology, and Department of Medicine, University of Maryland School of Medicine, Baltimore; 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