In vitro activity of oxazaphosphorines in childhood acute leukemia: preliminary report.
Glufosfamide (beta-D-glucosyl-ifosfamide mustard) is a new agent for cancer chemotherapy. Its pharmacology is similar to commonly used oxazaphosphorines, but it does not require activation by hepatic cytochrome P-450 and preclinically demonstrates lower nephrotoxicity and myelosuppression than ifosfamide. The aim of the study was a comparison of the drug resistance profiles of glufosfamide and other oxazaphosphorines in childhood acute leukemias. Leukemic cells, taken from children with ALL on diagnosis (n = 41), ALL on relapse (n = 12) and AML on diagnosis (n = 13) were analyzed by means of the MTT assay. The following drugs were tested: glufosfamide (GLU), 4-HOO-ifosfamide (IFO), 4-HOO-cyclophosphamide (CYC) and mafosfamide cyclohexylamine salt (MAF). In the group of initial ALL samples median cytotoxicity values for GLU, IFO, CYC and MAF were 15.5, 33.8, 15.7 and 7.8 microM, respectively. In comparison with initial ALL samples, the relative resistance for GLU and IFO in relapsed ALL samples was 1.9 (p = 0.049) and 1.3 (ns), and in initial AML samples 31 (p < 0.001) and 5 (p = 0.001), respectively. All oxazaphosphorines presented highly significant cross-resistance. Glufosfamide presented high activity against lymphoblasts both on diagnosis and on relapse.
Department of Pediatric Hematology and Oncology, Medical University, Bydgoszcz, Poland. jan_styczynski@kki.net.pl
Jan
J
Styczyński
Mariusz
M
Wysocki
Robert
R
Debski
Walentyna
W
Balwierz
Roma
R
Rokicka-Milewska
Michał
M
Matysiak
Anna
A
Balcerska
Jerzy
J
Kowalczyk
Jacek
J
Wachowiak
Danuta
D
Sońta-Jakimczyk
Alicja
A
Chybicka
D000293:Adolescent; 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; D066298:In Vitro Techniques; 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*; D014407:Tumor Cells, Cultured / Q000187:drug effects
C093853:4-hydroxyperoxycyclophosphamide; D010752:Phosphoramide Mustards; C092028:beta-D-glucosylisophosphoramide mustard; C037933:Asta Z 7557; D003520:Cyclophosphamide; D005947:Glucose; D007069:Ifosfamide