Cytotoxic combination of loxoribine with fludarabine and mafosfamide on freshly isolated B-chronic lymphocytic leukemia cells.

Abstract	Fludarabine has shown a definite clinical activity in B-cell chronic lymphocytic leukemia (B-CLL). Recently it has been demonstrated that loxoribine, a guanine ribonucleotide derivative, is able to increase the cytotoxicity of fludarabine in B-CLL cells, in vitro. We have here extended these findings by testing the activity of loxoribine in combination with fludarabine and mafosfamide. As we have previously demonstrated, loxoribine enhances the activity of fludarabine at all concentrations, while only lower doses of mafosfamide seem to be positively affected by loxoribine. The combination of fludarabine and mafosfamide is synergistic on CLL cells, and the cytotoxic activity is increased by the addition of loxoribine. We have also evaluated the pro-apoptotic activity of each drug, both alone and in combination; these results are concordant with the cytotoxicity data, thus demonstrating that, even though loxoribine is more active in combination with fludarabine than with mafosfamide, the efficacy of the triple combination is higher than that obtained with any other agent alone or in double combination.
Authors	A Pellacani, P Tosi, P L Zinzani, E Ottaviani, P Albertini, M Magagnoli, S Tura
Journal	Leukemia & lymphoma (Leuk Lymphoma) Vol. 33 Issue 1-2 Pg. 147-53 (Mar 1999) ISSN: 1042-8194 [Print] United States
PMID	10194132 (Publication Type: Journal Article)
Chemical References	Adjuvants, Immunologic Guanosine mafosfamide Cyclophosphamide loxoribine Vidarabine fludarabine
Topics	Adjuvants, Immunologic (administration & dosage, toxicity) Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols (administration & dosage, toxicity) Apoptosis Cell Division (drug effects) Cyclophosphamide (administration & dosage, analogs & derivatives, toxicity) Drug Screening Assays, Antitumor Drug Therapy, Combination Female Guanosine (administration & dosage, analogs & derivatives, toxicity) Humans Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, pathology) Male Middle Aged Tumor Cells, Cultured Vidarabine (administration & dosage, analogs & derivatives, toxicity)

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