TY - JOUR
T1 - A phase II study of continuous infusion of trimetrexate in patients with refractory acute leukemia
AU - Kheradpour, Albert
AU - Berman, Ellin
AU - Göker, Erdem
AU - Lin, James T.
AU - Tong, William P.
AU - Bertino, Joseph R.
N1 - Funding Information:
This work was supported by a grant from the American Cancer Society (ACS-DHP 181).
PY - 1995
Y1 - 1995
N2 - Trimetrexate, a second-generation folate antagonist, is a potent inhibitor of dihydrofolate reductase with a broader spectrum of activity and different mechanism of entry and intracellular accumulation than methotrexate. Six patients with refractory or relapsed acute leukemia were treated with a 5-day continuous infusion of trimetrexate of 8 mg/m2 /day after an initial loading dose of 4 mg/m2 to achieve a target plasma concentration of 0.2-0.5 μM. In 4 patients with peripheral blasts at study entry, transient decrease or disappearance of blasts was observed, although no decrease of bone marrow blasts occurred. Mucositis was dose-limiting and severe in 4 patients. Neutrophil and platelet nadirs occurred on day 5-12 postinfusion. Because of dose-limiting mucositis, this dose schedule of trimetrexate is not recommended for further studies in refractory acute leukemia. However, other dose schedules (24- to 72-hr infusions) and its use as a modulating agent with thiopurines or leucovorin in patients that are resistant to methotrexate should be explored.
AB - Trimetrexate, a second-generation folate antagonist, is a potent inhibitor of dihydrofolate reductase with a broader spectrum of activity and different mechanism of entry and intracellular accumulation than methotrexate. Six patients with refractory or relapsed acute leukemia were treated with a 5-day continuous infusion of trimetrexate of 8 mg/m2 /day after an initial loading dose of 4 mg/m2 to achieve a target plasma concentration of 0.2-0.5 μM. In 4 patients with peripheral blasts at study entry, transient decrease or disappearance of blasts was observed, although no decrease of bone marrow blasts occurred. Mucositis was dose-limiting and severe in 4 patients. Neutrophil and platelet nadirs occurred on day 5-12 postinfusion. Because of dose-limiting mucositis, this dose schedule of trimetrexate is not recommended for further studies in refractory acute leukemia. However, other dose schedules (24- to 72-hr infusions) and its use as a modulating agent with thiopurines or leucovorin in patients that are resistant to methotrexate should be explored.
UR - https://www.scopus.com/pages/publications/0028800680
UR - https://www.scopus.com/pages/publications/0028800680#tab=citedBy
U2 - 10.3109/07357909509024893
DO - 10.3109/07357909509024893
M3 - Article
C2 - 7834472
SN - 0735-7907
VL - 13
SP - 36
EP - 40
JO - Cancer Investigation
JF - Cancer Investigation
IS - 1
ER -