TY - JOUR
T1 - Phase I trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients with advanced multiple myeloma
AU - Richardson, Paul
AU - Mitsiades, Constantine
AU - Colson, Kathleen
AU - Reilly, Eileen
AU - McBride, Laura
AU - Chiao, Judy
AU - Sun, Linda
AU - Ricker, Justin
AU - Rizvi, Syed
AU - Oerth, Carol
AU - Atkins, Barbara
AU - Fearen, Ivy
AU - Anderson, Kenneth
AU - Siegel, David
N1 - Funding Information:
This study was supported by research funding from Merck Research Laboratories. Dr. C.S. Mitsiades has received in the past Consultant honoraria from Millennium Pharmaceuticals, Novartis Pharmaceuticals, Bristol-Myers Squibb, Merck & Co. and Pharmion and has received research funding from Amgen Pharmaceuticals, AVEO Pharma, EMD Serono and Sunesis Pharmaceuticals.
PY - 2008/3
Y1 - 2008/3
N2 - A Phase I trial (NCT00109109) of oral vorinostat 200, 250 or 300 mg twice daily for 5 days/week/4-week cycle or 200, 300, or 400 mg twice daily for 14 days/3-week cycle until progressive disease or intolerable toxicity was conducted. Patients with measurable, relapsed/refractory multiple myeloma were eligible. The objectives were to determine maximum tolerated doses (MTDs) and assess activity and safety. Thirteen patients (median age, 63 years; median prior therapies, 3) were enrolled. MTDs were not determined due to early study termination by sponsor decision. One patient (250 mg twice daily 5 days/week) developed dose-limiting toxicity (DLT; grade 3 fatigue). There were no other DLTs and the maximum administered doses were 250 mg twice daily for 5 days/week/ 4-week cycle and 200 mg twice daily for 14 days/3-week cycle. Drug-related adverse experiences included fatigue, anorexia, dehydration, diarrhea, and nausea and were mostly grade ≤2. Of 10 evaluable patients, 1 had a minimal response and 9 had stable disease, demonstrating modest single-agent activity in relapsed/refractory multiple myeloma.
AB - A Phase I trial (NCT00109109) of oral vorinostat 200, 250 or 300 mg twice daily for 5 days/week/4-week cycle or 200, 300, or 400 mg twice daily for 14 days/3-week cycle until progressive disease or intolerable toxicity was conducted. Patients with measurable, relapsed/refractory multiple myeloma were eligible. The objectives were to determine maximum tolerated doses (MTDs) and assess activity and safety. Thirteen patients (median age, 63 years; median prior therapies, 3) were enrolled. MTDs were not determined due to early study termination by sponsor decision. One patient (250 mg twice daily 5 days/week) developed dose-limiting toxicity (DLT; grade 3 fatigue). There were no other DLTs and the maximum administered doses were 250 mg twice daily for 5 days/week/ 4-week cycle and 200 mg twice daily for 14 days/3-week cycle. Drug-related adverse experiences included fatigue, anorexia, dehydration, diarrhea, and nausea and were mostly grade ≤2. Of 10 evaluable patients, 1 had a minimal response and 9 had stable disease, demonstrating modest single-agent activity in relapsed/refractory multiple myeloma.
KW - Histone deacetylase inhibitor
KW - Multiple myeloma
KW - SAHA
KW - Suberoylanilide hydroxamic acid
KW - Vorinostat
KW - Zolinza
UR - http://www.scopus.com/inward/record.url?scp=39749103428&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39749103428&partnerID=8YFLogxK
U2 - 10.1080/10428190701817258
DO - 10.1080/10428190701817258
M3 - Article
C2 - 18297527
AN - SCOPUS:39749103428
SN - 1042-8194
VL - 49
SP - 502
EP - 507
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 3
ER -