A phase 1b/2 study of vosaroxin in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia.
Vosaroxin is a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II. This study assessed the safety and tolerability of vosaroxin plus cytarabine in patients with relapsed/refractory acute myeloid leukemia. Escalating vosaroxin doses (10-minute infusion; 10-90 mg/m(2); days 1, 4) were given in combination with cytarabine on one of two schedules: schedule A (24-hour continuous intravenous infusion, 400 mg/m(2)/day, days 1-5) or schedule B (2-hour intravenous infusion, 1 g/m(2)/day, days 1-5). Following dose escalation, enrollment was expanded at the maximum tolerated dose. Of 110 patients enrolled, 108 received treatment. The maximum tolerated dose of vosaroxin was 80 mg/m(2) for schedule A (dose-limiting toxicities: grade 3 bowel obstruction and stomatitis) and was not reached for schedule B (recommended phase 2 dose: 90 mg/m(2)). In the efficacy population (all patients in first relapse or with primary refractory disease treated with vosaroxin 80-90 mg/m(2); n=69), the complete remission rate was 25% and the complete remission/complete remission with incomplete blood count recovery rate was 28%. The 30-day all-cause mortality rate was 2.5% among all patients treated at a dose of 80-90 mg/m(2). Based upon these results, a phase 3 trial of vosaroxin plus cytarabine was initiated in patients with relapsed/refractory acute myeloid leukemia. (Clinicaltrials.gov identifier: NCT00541866).
Moffitt Cancer Center, Tampa, FL jeffrey.lancet@moffitt.org.
Jeffrey E
JE
Lancet
Cornell University/New York Presbyterian Hospital, New York, NY.
Gail J
GJ
Roboz
Indiana University Cancer Center, Indianapolis, IN.
Larry D
LD
Cripe
Sunesis Pharmaceuticals, Inc., South San Francisco, CA.
Glenn C
GC
Michelson
Sunesis Pharmaceuticals, Inc., South San Francisco, CA.
Judith A
JA
Fox
PharmaPacific, Inc., Woodside, CA.
Richard D
RD
Leavitt
Sunesis Pharmaceuticals, Inc., South San Francisco, CA.
Tianling
T
Chen
Sunesis Pharmaceuticals, Inc., South San Francisco, CA.
Rachael
R
Hawtin
Sunesis Pharmaceuticals, Inc., South San Francisco, CA.
Adam R
AR
Craig
MD Anderson Cancer Center, Houston, TX.
Farhad
F
Ravandi
Rocky Mountain Blood and Marrow Transplant Center, Denver, CO.
Michael B
MB
Maris
Medical University of South Carolina, Charleston, SC.
Robert K
RK
Stuart
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
Judith E
JE
Karp
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D003561:Cytarabine / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009287:Naphthyridines / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D013844:Thiazoles / Q000008:administration & dosage; D055815:Young Adult
D009287:Naphthyridines; D013844:Thiazoles; D003561:Cytarabine; C485113:vosaroxin