Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma.
OBJECTIVE
To evaluate the activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in persistent, progressive, or recurrent mycosis fungoides or Sézary syndrome (MF/SS) cutaneous t-cell lymphoma (CTCL) subtypes.


METHODS
Patients with stage IB-IVA MF/SS were treated with 400 mg of oral vorinostat daily until disease progression or intolerable toxicity in this open-label phase IIb trial (NCT00091559). Patients must have received at least two prior systemic therapies at least one of which included bexarotene unless intolerable. The primary end point was the objective response rate (ORR) measured by the modified severity weighted assessment tool and secondary end points were time to response (TTR), time to progression (TTP), duration of response (DOR), and pruritus relief ( > or = 3-point improvement on a 10-point visual analog scale). Safety and tolerability were also evaluated.


RESULTS
Seventy-four patients were enrolled, including 61 with at least stage IIB disease. The ORR was 29.7% overall; 29.5% in stage IIB or higher patients. Median TTR in stage IIB or higher patients was 56 days. Median DOR was not reached but estimated to be >or = 185 days (34+ to 441+). Median TTP was 4.9 months overall, and 9.8 months for stage IIB or higher responders. Overall, 32% of patients had pruritus relief. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%), and anorexia (26%); most were grade 2 or lower but those grade 3 or higher included fatigue (5%), pulmonary embolism (5%), thrombocytopenia (5%), and nausea (4%). Eleven patients required dose modification and nine discontinued due to AE.


CONCLUSIONS
Oral vorinostat was effective in treatment refractory MF/SS with an acceptable safety profile.
Olsen
Elise A
EA
Duke University, Durham, NC, USA. olsen001@mc.duke.edu
Kim
Youn H
YH
Kuzel
Timothy M
TM
Pacheco
Theresa R
TR
Foss
Francine M
FM
Parker
Sareeta
S
Frankel
Stanley R
SR
Chen
Cong
C
Ricker
Justin L
JL
Arduino
Jean Marie
JM
Duvic
Madeleine
M
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011336:Probability; D016879:Salvage Therapy; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D000077337:Vorinostat
D006877:Hydroxamic Acids; D000077337:Vorinostat