Potential efficacy of the oral histone deacetylase inhibitor vorinostat in a phase I trial in follicular and mantle cell lymphoma.
Vorinostat (suberoylanilide hydroxamic acid, SAHA, Zolinza) is a histone deacetylase inhibitor with clinical activity in cutaneous T-cell lymphoma (CTCL). A phase I trial of oral vorinostat was conducted in Japanese patients with malignant lymphoma. Vorinostat 100 or 200 mg was administered twice daily for 14 consecutive days followed by a 1-week rest interval. Of 10 patients enrolled, four had follicular lymphoma (FL), two mantle cell lymphoma (MCL), two diffuse large B-cell lymphoma, and two CTCL (median age, 60 years; median number of prior regimens, 3). Vorinostat was well tolerated up to 200 mg with only one of six patients developing a dose-limiting toxicity (DLT; Grade 3 anorexia/hypokalemia). Common Grade 3 events were reversible neutropenia (30%), thrombocytopenia, and hypermagnesemia (20% each). The median number of treatment cycles was five (range, 1-36); two patients were continuing treatment. The overall response rate was 40%, with two complete responses/unconfirmed (CRu) and one partial response among FL patients and one CRu among MCL patients. One FL patient maintained CRu for 18.0 months. The median time to achieve CRu among the three patients was 8 months. These data suggest that further investigations of vorinostat in non-Hodgkin lymphoma, focusing on FL and MCL, are warranted.
Watanabe
Takashi
T
Hematology and Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan. takawata@ncc.go.jp
Kato
Harumi
H
Kobayashi
Yukio
Y
Yamasaki
Satoshi
S
Morita-Hoshi
Yuriko
Y
Yokoyama
Hiroki
H
Morishima
Yasuo
Y
Ricker
Justin L
JL
Otsuki
Tetsuya
T
Miyagi-Maesima
Akiko
A
Matsuno
Yoshihiro
Y
Tobinai
Kensei
K
D000284:Administration, Oral; D000368:Aged; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000077337:Vorinostat
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat