A phase II study of topical ceramides for cutaneous breast cancer.
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.
Jatoi
Aminah
A
Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. jatoi.aminah@mayo.edu
Suman
Vera J
VJ
Schaefer
Paul
P
Block
Margaret
M
Loprinzi
Charles
C
Roche
Patrick
P
Garneau
Stuart
S
Morton
Roscoe
R
Stella
Philip J
PJ
Alberts
Steven R
SR
Pittelkow
Mark
M
Sloan
Jeff
J
Pagano
Richard
R
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
D000970:Antineoplastic Agents; D002518:Ceramides