Phase I/II study of idarubicin given with continuous infusion fludarabine followed by continuous infusion cytarabine in children with acute leukemia: a report from the Children's Cancer Group.

Abstract

This combination is active in patients with relapsed or refractory AML. The major toxicity encountered is hematologic. This regimen may be useful therapy for AML and should be compared with standard induction therapy in children with newly diagnosed AML.

In vitro cytotoxic effects of fludarabine (2-F-ara-A) in combination with commonly used antileukemic agents by isobologram analysis

“…Clinical studies of fludarabine phosphate with topo-II inhibitors have been carried out against leukemia and lymphoma. [19][20][21][22] In our study, 2-F-ara-A in combination with doxorubicin showed additive effects for three cell lines and Leukemia synergistic/additive effects for one cell line, while 2-F-ara-A in combination with etoposide showed additive effects in all four cell lines. These findings suggest that the simultaneous administration of fludarabine phosphate with doxorubicin or etoposide would have the expected activity.…”

“…The clinical study of the fludarabine phosphate/cytarabine sequence produced a high response rate. 16,17,21 The decreased cellular deoxynucleotide concentration due to the inhibition of ribonucleotide reductase by 2-F-ara-ATP is associated with an increase in the rate of cytarabine phosphorylation by deoxycytidine kinase. 16,27 This is considered to be the major mechanism of the synergistic interaction of sequential exposure to 2-F-ara-A or fludarabine phosphate followed by cytarabine.…”

“…7,8 Fludarabine phosphate has promising therapeutic effects in the treatment of chronic lymphocytic leukemia, lymphoma, and acute leukemia. [9][10][11][12][13][14] Most clinical regimens incorporate two or more drugs in combination, and fludarabine phosphate has been combined with a variety of agents. [15][16][17][18][19][20][21][22][23][24][25] Although 2-F-ara-A has been reported to show synergistic effects with cytarabine and cisplatin, there are few experimental data available about the combination of 2-F-ara-A and other anticancer agents which are active against leukemia and lymphoma.…”

“…[9][10][11][12][13][14] Most clinical regimens incorporate two or more drugs in combination, and fludarabine phosphate has been combined with a variety of agents. [15][16][17][18][19][20][21][22][23][24][25] Although 2-F-ara-A has been reported to show synergistic effects with cytarabine and cisplatin, there are few experimental data available about the combination of 2-F-ara-A and other anticancer agents which are active against leukemia and lymphoma. [26][27][28][29][30][31][32][33] In the present study, we investigated the in vitro effects of 2-F-ara-A in combination with cytarabine, doxorubicin, etoposide, 4-hydroperoxy-cyclophosphamide, hydroxyurea, methotrexate, and vincristine against four human leukemia cell lines.…”

Modulation of ara-CTP levels by fludarabine and hydroxyurea in leukemic cells

“…[11][12][13][14][15] Since in vitro studies have shown a two-to three-fold increase of ara-CTP levels in AML and CLL blasts, 16 and ALL in adults and children. [18][19][20][21][22][23] Data on intracellular ara-C metabolism under these regimens are rare. 18 Notwithstanding the large number of in vitro studies, F-ara-A has never been tested systematically as a modifier of ara-C toxification in different subtypes of acute leukemia, especially in lymphoblastic cells.…”