Abstract | BACKGROUND AND OBJECTIVE: DESIGN AND METHODS: In the in vivo part of our study, mice bearing L1210 or P388 leukemia were treated with dFdC and Ara-C. The drugs were administered alone and in combination according to the following schedules: Ara-C and dFdC at the same time, dFdC before Ara-C, and Ara-C before dFdC. The efficacy of the therapy against leukemia (defined as the increase in lifespan, ILS) was assessed as the percentage of the median survival time (MST) of the treated group (T) in relationship to that of the control group (C): ILS=[(MST(C)/MST(T)) -1]x100. In the in vitro part of our study, normal granulocyte-macrophage colony-forming unit (CFU-GM) cells as well as CFU-GM cells obtained from patients with chronic myeloid leukemia (CML) were incubated either with dFdC or Ara-C alone or with adequate concentrations of a combination of these drugs. RESULTS: The in vivo experiment revealed that in both leukemias tested, combined therapy with dFdC given before Ara-C and dFdC given at the same time with Ara-C were more effective than monotherapy with either dFdC or Ara-C. The other treatment schedule ( Ara-C before dFdC) did not significantly prolong the survival time of the treated mice bearing L1210 or P388 leukemia as compared with the treatment with dFdC alone. The in vitro experiments showed that dFdC used together with Ara-C acted additively on normal as well as CML CFU-GM cells. Furthermore, the drugs used jointly inhibited the growth of colonies formed by CML CFU-GM cells to a significantly higher degree than normal CFU-GM and the differences were statistically significant in the case of the combination of highest concentrations. INTERPRETATION AND CONCLUSIONS:
Gemcitabine increased the activity of Ara-C. As these agents incorporate into DNA blocking chain elongation, and moreover, dFdC influences the cytotoxicity of Ara-C, our results could be explained by the drugs acting at these levels. dFdC used jointly with Ara-C may have an important clinical implication in the treatment of CML and other hematologic malignancies in future.
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Authors | E Lech-Maranda, A Korycka, T Robak |
Journal | Haematologica
(Haematologica)
Vol. 85
Issue 6
Pg. 588-94
(Jun 2000)
ISSN: 0390-6078 [Print] Italy |
PMID | 10870114
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antimetabolites, Antineoplastic
- Cytarabine
- Deoxycytidine
- Gemcitabine
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Topics |
- Animals
- Antimetabolites, Antineoplastic
(pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology)
- Cell Culture Techniques
- Cytarabine
(pharmacology)
- Deoxycytidine
(analogs & derivatives, pharmacology)
- Humans
- Leukemia, Experimental
(drug therapy)
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
(pathology)
- Male
- Mice
- Mice, Inbred Strains
- Stem Cells
(drug effects)
- Tumor Cells, Cultured
(transplantation)
- Gemcitabine
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