title: A phase II study of topical ceramides for cutaneous breast cancer.
abstract: OBJECTIVE
  Short chain ceramides induce tumor cell apoptosis in preclinical models. Limited therapeutic options for patients with cutaneous breast cancer prompted the testing of these sphingolipids in patients with this disease.
  
  
  METHODS
  Twenty-five patients with refractory, cutaneous breast cancer were treated twice a day with a 1% mixture of topical C2 and C6 ceramides administered in a 1:1 ratio. For the first 8 weeks, patients were not allowed to receive other antineoplastic therapy. In addition to tumor status and toxicity assessment throughout the trial, skin biopsies for evidence of apoptosis and quality of life questionnaires (FACT-BR) were completed at baseline and 1 month.
  
  
  RESULTS
  Only one patient manifested a partial response with topical ceramides, yielding a response rate of 4% (90% confidence interval 0, 17.6%). Median cutaneous progression-free survival was 2 months. The topical ceramides were also well tolerated, with no grade 3 or 4 toxicity reported. None of the six patients who underwent serial skin biopsies showed increased tumor cell apoptosis morphologically or by the modified TUNEL assay.
  
  
  CONCLUSIONS
  To our knowledge, this trial is one of the first clinical investigations of short chain ceramides. This trial's results are not promising enough to merit further study of ceramides in the manner prescribed.
authors.affiliation: Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. jatoi.aminah@mayo.edu
authors.forename: Aminah
authors.initials: A
authors.lastname: Jatoi
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.forename: Paul
authors.initials: P
authors.lastname: Schaefer
authors.forename: Margaret
authors.initials: M
authors.lastname: Block
authors.forename: Charles
authors.initials: C
authors.lastname: Loprinzi
authors.forename: Patrick
authors.initials: P
authors.lastname: Roche
authors.forename: Stuart
authors.initials: S
authors.lastname: Garneau
authors.forename: Roscoe
authors.initials: R
authors.lastname: Morton
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stella
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.forename: Mark
authors.initials: M
authors.lastname: Pittelkow
authors.forename: Jeff
authors.initials: J
authors.lastname: Sloan
authors.forename: Richard
authors.initials: R
authors.lastname: Pagano
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D002518:Ceramides / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D018579:Patient Selection; D011446:Prospective Studies; D011788:Quality of Life; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D002518:Ceramides