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2002 | 49 | 1 | 221-225
Article title

In vitro activity of oxazaphosphorines in childhood acute leukemia: Preliminary report.

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Abstracts
EN
Glufosfamide (β-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 μM, 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.
Keywords
Publisher

Year
Volume
49
Issue
1
Pages
221-225
Physical description
Dates
published
2002
received
2001-09-10
revised
2002-01-03
accepted
2002-02-21
Contributors
  • Department of Pediatric Hematology and Oncology, Medical University, Bydgoszcz, Poland
  • Department of Pediatric Hematology and Oncology, Medical University, Bydgoszcz, Poland
  • Department of Pediatric Hematology and Oncology, Medical University, Bydgoszcz, Poland
  • Department of Pediatric Hematology, Collegium Medicum Jagiellonian University, Kraków, Poland
  • Department of Pediatric Hematology and Oncology, Medical University, Warszawa, Poland
  • Department of Pediatric Pulmonology, Alergology and Hematology, Medical University, Warszawa, Poland
  • Department of Pediatric Hematology, Oncology and Endocrinology, Medical University, Gdańsk, Poland
  • Department of Pediatric Hematology and Oncology, Medical University, Lublin, Poland
  • Department of Pediatric Hematology and Oncology, Medical University, Poznań, Poland
  • Department of Pediatric Hematology and Chemotherapy, Silesian Medical University, , Zabrze, Poland
  • Department of Pediatric Hematology and Oncology, Medical University, Wrocław, Poland
References
  • 1. Brock, N., Hilgard, P., Peukert, M., Pohl, J. & Sindermann, H. (1988) Basis and new developments in the field of oxazaphosphorines. Cancer Invest. 6, 513-532.
  • 2. Hilgard, P. & Pohl, J. (1986) Short communication: Cause and prevention of mafosfamide- induced venous pain. Invest. New Drugs 4, 373-376.
  • 3. Niemeyer, U., Engel, J., Hilgard, P., Peukert, M., Pohl, J. & Sindermann, H. (1989) Mafosfamide - a derivative of 4-hydroxycyclophosphamide. Prog. Clin. Biochem. Med. 9, 35-60.
  • 4. Pohl, J., Bertram, B., Hilgard, P., Nowrousian, M.R., Stuben, J. & Wiessler, M. (1995) D-19575 - a sugar-linked isophosphoramide mustard derivative exploiting transmembrane glucose transport. Cancer Chemother. Pharmacol. 35, 364-370.
  • 5. Stuben, J., Port, R., Bertram, B., Bollow, U., Hull, W.E., Schaper, M., Pohl, J. & Wiessler, M. (1996) Pharmacokinetics and whole-body distribution of the new chemotherapeutic agent beta-D-glucosylisophosphoramide mustard and its effects on the incorporation of [methyl-3H]-thymidine in various tissues of the rat. Cancer Chemother. Pharmacol. 38, 355-365.
  • 6. Veyhl, M., Wagner, K., Volk, C., Gorboulev, V., Baumgarten, K., Weber, W.M., Schaper, M., Bertram, B., Wiessler, M. & Koepsell, H. (1998) Transport of the new chemotherapeutic agent beta-D-glucosylisophosphoramide mustard (D-19575) into tumor cells is mediated by the Na+-D-glucose cotransporter SAAT1. Proc. Natl. Acad. Sci. U.S.A. 95, 2914-2919.
  • 7. Seker, H., Bertram, B., Burkle, A., Kaina, B., Pohl, J., Koepsell, H. & Wiesser, M. (2000) Mechanistic aspects of the cytotoxic activity of glufosfamide, a new tumour therapeutic agent. Br. J. Cancer 82, 629-634.
  • 8. Styczyński, J., Pieters, R., Huismans, D.R., Schuurhuis, G.J., Wysocki, M. & Veerman, A.J.P. (2000) In vitro drug resistance profiles in adult versus childhood acute lymphoblastic leukemia. Br. J. Haematol. 110, 813-818.
  • 9. Makrynikola, V., Kabral, A. & Bradstock, K.F. (1991) Effect of mafosfamide (ASTA-Z-7654) on the clonogenic cells in precursor-B acute lymphoblastic leukaemia: Significance for ex vivo purging of bone marrow for autologous transplantation. Bone Marrow Transplant. 8, 351-355.
Document Type
Publication order reference
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YADDA identifier
bwmeta1.element.bwnjournal-article-abpv49i1p221kz
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