title: Phase I trial of fenretinide lym-x-sorb oral powder in adults with solid tumors and lymphomas.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Cancer Institute, Building 31, Room 3A44, 31 Center Drive, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Shivaani
authors.initials: S
authors.lastname: Kummar
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gutierrez
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Maurer
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Reynolds
authors.forename: Min
authors.initials: M
authors.lastname: Kang
authors.forename: Hardeep
authors.initials: H
authors.lastname: Singh
authors.forename: Sonja
authors.initials: S
authors.lastname: Crandon
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Murgo
authors.forename: James H
authors.initials: JH
authors.lastname: Doroshow
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D017313:Fenretinide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008223:Lymphoma / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011208:Powders
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D011208:Powders; D017313:Fenretinide