title: In vitro activity of glufosfamide in childhood acute leukemia.
abstract: Glufosfamide is a new agent for cancer chemotherapy. The objective of the study was the comparison of the in vitro drug resistance profile of glufosfamide with other oxazaphosphorines in 106 samples of childhood acute leukemia by means of the MTT assay. The following drugs were tested: glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide, mafosfamide cyclohexylamine salt, prednisolone, vincristine, L-asparaginase, daunorubicin and cytarabine. In the group of initial Acute Lymphoblastic Leukemia (ALL) samples, equivalent cytotoxicity values for glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide and mafosfamide were 5.95, 9.92, 4.60 and 3.90 microg/ml, respectively. In comparison to initial ALL samples, the relative resistance for glufosfamide and 4-HOO-ifosfamide in relapsed ALL samples were 1.9 (p=0.049) and 1.3 (ns), and in initial Acute Myeloblastic Leukemia (AML) samples, respectively, 31 (p<0.001) and 5 (p=0.001). All oxazaphosphorines showed highly significant cross-resistance. In conclusion, in vitro activity of glufosfamide is comparable to ifosfamide. Glufosfamide shows high activity against lymphoblasts both on diagnosis and on relapse, however it cannot circumvent resistance to other oxazaphosphorines.
authors.affiliation: Katedra i Klinika Pediatrii, Hematologii i Onkologii, Bydgoszcz, Poland. jan_styczynski@kki.net.pl
authors.forename: Jan
authors.initials: J
authors.lastname: Styczynski
authors.forename: Mariusz
authors.initials: M
authors.lastname: Wysocki
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kurylak
authors.forename: Edyta
authors.initials: E
authors.lastname: Juraszewska
authors.forename: Iwona
authors.initials: I
authors.lastname: Malinowska
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Stanczak
authors.forename: Anna
authors.initials: A
authors.lastname: Płoszynska
authors.forename: Jolanta
authors.initials: J
authors.lastname: Stefaniak
authors.forename: Benigna
authors.initials: B
authors.lastname: Mazur
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szczepanski
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Ras
mesh_terms: D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000031:analogs & derivatives; D006801:Humans; D007069:Ifosfamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D010752:Phosphoramide Mustards / Q000494:pharmacology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D018906:Antineoplastic Agents, Alkylating; D010752:Phosphoramide Mustards; D013778:Tetrazolium Salts; D013844:Thiazoles; C092028:beta-D-glucosylisophosphoramide mustard; C048341:mafosfamide; D003520:Cyclophosphamide; C039771:4-hydroxyifosfamide; C022616:thiazolyl blue; D005947:Glucose; D007069:Ifosfamide