To Combine or Not Combine: Drug Interactions and Tools for Their Analysis. Reflections from the EORTC-PAMM Course on Preclinical and Early-phase Clinical Pharmacology.

Abstract:

:Combination therapies are used in the clinic to achieve cure, better efficacy and to circumvent resistant disease in patients. Initial assessment of the effect of such combinations, usually of two agents, is frequently performed using in vitro assays. In this review, we give a short summary of the types of analyses that were presented during the Preclinical and Early-phase Clinical Pharmacology Course of the Pharmacology and Molecular Mechanisms Group, European Organization for Research and Treatment on Cancer, that can be used to determine the efficacy of drug combinations. The effect of a combination treatment can be calculated using mathematical equations based on either the Loewe additivity or Bliss independence model, or a combination of both, such as Chou and Talalay's median-drug effect model. Interactions can be additive, synergistic (more than additive), or antagonistic (less than additive). Software packages CalcuSyn (also available as CompuSyn) and Combenefit are designed to calculate the extent of the combined effects. Interestingly, the application of machine-learning methods in the prediction of combination treatments, which can include pharmacogenomic, genetic, metabolomic and proteomic profiles, might contribute to further refinement of combination regimens. However, more research is needed to apply appropriate rules of machine learning methods to ensure correct predictive models.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

El Hassouni B,Mantini G,Li Petri G,Capula M,Boyd L,Weinstein HNW,Vallés-Marti A,Kouwenhoven MCM,Giovannetti E,Westerman BA,Peters GJ,EORTC PAMM Group.

doi

10.21873/anticanres.13472

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

3303-3309

issue

7

eissn

0250-7005

issn

1791-7530

pii

39/7/3303

journal_volume

39

pub_type

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