title: Tamoxifen and fenretinide in women with metastatic breast cancer.
abstract: BACKGROUND
  Tamoxifen and fenretinide combination therapy has been shown to be an active treatment regimen in metastatic breast cancer patients. This pilot study sought to determine whether the addition of fenretinide to tamoxifen would be associated with antitumor activity in metastatic breast cancer patients who had been previously treated with tamoxifen or who had hormone receptor negative disease. The effect of this therapy on circulating plasma transforming growth factor-beta (TGF-beta) levels and serum lipids was also examined.
  
  
  METHODS
  Thirty-one patients were treated with tamoxifen (20 mg p.o. daily), and fenretinide (400 mg p.o. daily with a 3-day drug holiday each month). Plasma TGF-beta testing was performed using isoform specific sandwich ELISA.
  
  
  RESULTS
  Twenty four of the 31 patients were evaluable for an antitumor response including 14 estrogen receptor (ER) positive patients who had failed prior tamoxifen therapy, seven ER-negative patients, and three hormone therapy naive ER-positive patients. There were no objective antitumor responses; three patients had stable disease for 8, 8, and 24 months. Five patients (16%) discontinued therapy for toxicity (one for grade 3 skin rash and four for abnormal dark adaptation). There was a statistically significant decrease in total cholesterol (median change per patient of -13.5 mg/dl; p = 0.049, a 6.5% decrease), and an increase in HDL levels (median change per patient of +18 mg/dl, p = 0.0001, a 35% increase) with tamoxifen and fenretinide therapy. TGF-beta1 plasma levels were normal in 26 of 28 patients, and no changes in these levels post-treatment were demonstrated.
  
  
  CONCLUSIONS
  Tamoxifen and fenretinide therapy is not an active combination in ER negative metastatic breast cancer or in patients whose disease has progressed on tamoxifen. This combination had a beneficial effect on total serum cholesterol and HDL levels with no associated rise in serum triglyceride levels. The 400 mg dose of fenretinide was associated with symptomatic nyctalopia in one-third of patients making it an unsuitable dose for use in breast cancer prevention studies.
authors.affiliation: Medicine Branch, National Cancer Institute, Bethesda 20892, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zujewski
authors.forename: L
authors.initials: L
authors.lastname: Pai
authors.forename: L
authors.initials: L
authors.lastname: Wakefield
authors.forename: R
authors.initials: R
authors.lastname: Giusti
authors.forename: F A
authors.initials: FA
authors.lastname: Dorr
authors.forename: C
authors.initials: C
authors.lastname: Flanders
authors.forename: R
authors.initials: R
authors.lastname: Caruso
authors.forename: M
authors.initials: M
authors.lastname: Kaiser
authors.forename: L
authors.initials: L
authors.lastname: Goodman
authors.forename: M
authors.initials: M
authors.lastname: Merino
authors.forename: M
authors.initials: M
authors.lastname: Gossard
authors.forename: M A
authors.initials: MA
authors.lastname: Noone
authors.forename: A
authors.initials: A
authors.lastname: Denicoff
authors.forename: D
authors.initials: D
authors.lastname: Venzon
authors.forename: K H
authors.initials: KH
authors.lastname: Cowan
authors.forename: J A
authors.initials: JA
authors.lastname: O'Shaughnessy
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D017313:Fenretinide / Q000008:administration & dosage; D006801:Humans; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D010865:Pilot Projects; D013629:Tamoxifen / Q000008:administration & dosage; D016212:Transforming Growth Factor beta / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D008055:Lipids; D016212:Transforming Growth Factor beta; D013629:Tamoxifen; D017313:Fenretinide