In vitro testing of chemotherapeutic drug combinations in acute myelocytic leukaemia using the fluorometric microculture cytotoxicity assay (FMCA).

Abstract:

:The fluorometric microculture cytotoxicity assay (FMCA) was employed for analysing the effect of different chemotherapeutic drug combinations and their single constituents in 44 cases of acute myelocytic leukaemia (AML). A large heterogeneity with respect to cell kill was observed for all combinations tested, the interactions ranging from antagonistic to synergistic in terms of the multiplicative concept for drug interactions. However, an 'additive' model provided a significantly better fit of the data compared to the effect of the most active single agent of the combination (Dmax) for several common antileukaemic drug combinations. When the two interaction models were related to treatment outcome 38% of the non-responders showed preference for the additive model whereas the corresponding figure for responders was 80%. Overall, in 248 of 290 (85%) tests performed with drug combinations, there was an agreement between the effect of the combination and that of the most active single component. Direct comparison of Dmax and the combination for correlation with clinical outcome demonstrated only minor differences in the ability to predict drug resistance. The results show that FMCA appear to report drug interactions in samples from patients with AML in accordance with clinical experience. Furthermore, testing single agents as a substitute for drug combinations may be adequate for detection of clinical drug resistance to combination therapy in AML.

journal_name

Br J Cancer

authors

Larsson R,Fridborg H,Kristensen J,Sundström C,Nygren P

doi

10.1038/bjc.1993.178

subject

Has Abstract

pub_date

1993-05-01 00:00:00

pages

969-74

issue

5

eissn

0007-0920

issn

1532-1827

journal_volume

67

pub_type

临床试验,杂志文章
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    pub_type: 杂志文章

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    pub_type: 杂志文章

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    pub_type: 杂志文章,随机对照试验

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    pub_type: 杂志文章

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    pub_type: 临床试验,杂志文章,多中心研究

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  • DNA damage and repair in tumour and non-tumour tissues of mice induced by nicotinamide.

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    pub_type: 杂志文章

    doi:10.1038/bjc.1996.367

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    pub_type: 杂志文章

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    pub_type: 杂志文章

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  • Isolation and characterisation of a human anti-idiotypic scFv used as a surrogate tumour antigen to elicit an anti-HER-2/neu humoral response in mice.

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