Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL).
The activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) were evaluated in patients with refractory cutaneous T-cell lymphoma (CTCL). Group 1 received vorinostat 400 mg daily, group 2 received vorinostat 300 mg twice daily for 3 days with 4 days rest, and group 3 received vorinostat 300 mg twice daily for 14 days with 7 days rest followed by 200 mg twice daily. Treatment continued until disease progression or intolerable toxicity. The primary objective was to determine the complete and partial response (PR) rate. Time to response (TTR), time to progressive disease (TTP), response duration (DOR), pruritus relief, and safety were determined. Thirty-three patients who had received a median of 5 prior therapies were enrolled. Eight patients achieved a PR, including 7 with advanced disease and 4 with Sézary syndrome. The median TTR, DOR, and TTP for responders were 11.9, 15.1, and 30.2 weeks, respectively. Fourteen of 31 evaluable patients had pruritus relief. The most common drug-related AEs were fatigue, thrombocytopenia, diarrhea, and nausea. The most common grade 3 or 4 drug-related AEs were thrombocytopenia and dehydration. Vorinostat demonstrated activity in heavily pretreated patients with CTCL. The 400 mg daily regimen had the most favorable safety profile and is being further evaluated.
Duvic
Madeleine
M
Department of Dermatology, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 434, Houston, TX 77030-4409, USA. mduvic@mdanderson.org
Talpur
Rakshandra
R
Ni
Xiao
X
Zhang
Chunlei
C
Hazarika
Parul
P
Kelly
Cecilia
C
Chiao
Judy H
JH
Reilly
John F
JF
Ricker
Justin L
JL
Richon
Victoria M
VM
Frankel
Stanley R
SR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003681:Dehydration / Q000139:chemically induced; D018450:Disease Progression; D018572:Disease-Free Survival; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008214:Lymphocytes / Q000473:pathology; D016410:Lymphoma, T-Cell, Cutaneous / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011537:Pruritus / Q000188:drug therapy / Q000209:etiology; D012074:Remission Induction; D016879:Salvage Therapy; D012751:Sezary Syndrome / Q000150:complications / Q000188:drug therapy; D012867:Skin / Q000098:blood supply / Q000473:pathology; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D000077337:Vorinostat
D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D000077337:Vorinostat