Journal article
APPLICATION OF A NEW APPROACH FOR THE QUANTITATION OF DRUG SYNERGISM TO THE COMBINATION OF CIS-DIAMMINEDICHLOROPLATINUM AND 1-BETA-D-ARABINOFURANOSYLCYTOSINE
Cancer research (Chicago, Ill.), Vol.50(17), pp.5318-5327
09/01/1990
PMID: 2386940
Abstract
This report describes the application of a new approach, the universal response surface approach, to the quantitative assessment of drug interaction, i.e., the determination of synergism, antagonism, additivity, potentiation, inhibition, and coalitive action. The specific drug combination and experimental growth system for this introductory application was that of 1-beta-D-arabinofuranosylcytosine (ara-C) and cisplatin with simultaneous drug exposure (1, 3, 6, 12, or 48 h) against L1210 leukemia in vitro. To quantitate the type and degree of drug interaction, a model was fitted using nonlinear regression to the data from each separate experiment, and parameters were estimated (K. C. Syracuse and W. R. Greco, Proc. Biopharm. Sect. Am. Stat. Assoc., 127-132, 1986). The parameters included the maximum cell density over background in absence of drug, the background cell density in presence of infinite drug, the 50% inhibitory concentrations and concentration-effect slopes for each drug, and a synergism-antagonism parameter, alpha. A positive alpha indicates synergism, a negative alpha, antagonism, and a zero alpha, additivity. Maximal synergy was found with a 3-h exposure of ara-C + cisplatin, with alpha = 3.08 +/- 0.96 (SE) and 2.44 +/- 0.70 in two separate experiments. Four different graphic representations of the raw data and fitted curves provide visual indications of goodness of fit of the estimated dose-response surface to the data and visual indications of the intensity of drug interaction. The universal response surface approach is mathematically consistent with the traditional isobologram approach but is more objective, is more quantitative, and is more easily automated. Although specifically developed for in vitro cancer chemotherapy applications, the universal response surface approach should prove to be useful in the fields of pharmacology, toxicology, epidemiology, and biomedical science in general.
Details
- Title: Subtitle
- APPLICATION OF A NEW APPROACH FOR THE QUANTITATION OF DRUG SYNERGISM TO THE COMBINATION OF CIS-DIAMMINEDICHLOROPLATINUM AND 1-BETA-D-ARABINOFURANOSYLCYTOSINE
- Creators
- W R GrecoH S ParkY M Rustum
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.50(17), pp.5318-5327
- Publisher
- Amer Assoc Cancer Research
- PMID
- 2386940
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Number of pages
- 10
- Grant note
- CA184202; CA46732; CA50456 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01CA046732 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Comment
- Has Comment: Berenbaum MC. Re: W. R. Greco et al., Application of a new approach for the quantitation of drug synergism to the combination of cis-diamminedichloroplatinum and 1-beta-D-arabinofuranosylcytosine. Cancer Res. 1992 Aug 15;52(16):4558-60; PMID: 1643648.
- Language
- English
- Date published
- 09/01/1990
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984360039602771
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