Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome.
Triapine, an iron chelator and a potent inhibitor of ribonucleotide reductase, has significant anti-leukemia activity. A phase I study of Triapine in combination with ara-C was conducted in 32 patients with refractory acute leukemia and high-risk MDS. Triapine (105 mg/m2/day 6-h infusion) was followed immediately by ara-C [100 (n=4), 200 (n=6), 400 (n=7), or 800 (n=8)mg/m2/day] as an 18-h infusion for 5 consecutive days. Dose-limiting toxicities (DLTs) were observed at the 800 mg/m2 ara-C dose level (one patient each with grade 4 mucositis; grade 4 neutropenic colitis, sepsis; grade 4 neuropathy; and grade 4 hyperbilirubinemia). Therefore, the study was amended to include an ara-C dose level of 600 mg/m2/day, no DLTs occurred in seven patients treated at this dose level. Mean Triapine C(max) and AUC were 1.13 microg/mL and 251.5 minmicrog/mL. Of 31 evaluable patients, 4 (13%) (3 AML, 1 Ph+ALL) achieved a CR (1 at a dose of 800 mg/m2; 2 at 600 mg/m2; 1 at 200mg/m2). The recommended phase II regimen is Triapine 105 mg/m2/day followed by ara-C 600 mg/m2/day for 5 consecutive days every 3-6 weeks.
Department of Leukemia, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 428, Houston, TX 77030, USA.
Karen W L
KW
Yee
Jorge
J
Cortes
Alessandra
A
Ferrajoli
Guillermo
G
Garcia-Manero
Srdan
S
Verstovsek
William
W
Wierda
Deborah
D
Thomas
Stefan
S
Faderl
Ivan
I
King
Susan M
SM
O'brien
Sima
S
Jeha
Michael
M
Andreeff
Ann
A
Cahill
Mario
M
Sznol
Francis J
FJ
Giles
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy*; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D012008:Recurrence; D012307:Risk Factors; D013882:Thiosemicarbazones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
D004338:Drug Combinations; D011725:Pyridines; D013882:Thiosemicarbazones; D003561:Cytarabine; C078157:3-aminopyridine-2-carboxaldehyde thiosemicarbazone