Pharmaceutical Medicine

, Volume 22, Issue 2, pp 85–97

Challenges in Combinational Oncology Studies

Review Article

DOI: 10.1007/BF03256688

Cite this article as:
Macpherson, I.R.J. & Cassidy, J. Pharm Med (2008) 22: 85. doi:10.1007/BF03256688


The majority of effective systemic therapies in oncology are based on combinations of two or more drugs. The clinical benefits of combination over single-agent therapy may derive from enhanced cytotoxicity, abrogation of drug resistance or modulation of the tumour microenvironment. Previously, combinational oncology drug development focused on cytotoxic agents, which were selected on the basis of non-overlapping mechanisms of action and resistance, and preclinical evidence of synergy. Advances in basic science and drug discovery have led a shift towards the development of molecularly targeted agents that are combined with either cytotoxic chemotherapy or other targeted agents. The development of a novel drug combination presents significant scientific and regulatory challenges and requires integration of preclinical, clinical and correlative science to guide a series of go/no go decisions. Given the large number of potential drug combinations, the use of preclinical models that can identify the most promising combinations to advance to clinical testing is advocated. The majority of new combinations involve targeted agents for which an understanding of the mechanisms of efficacy and resistance, together with the validation of biomarkers predictive of response, will aid decision making at all stages of clinical development. This paper looks at the biological rationales and preclinical data that support combinational drug development and discusses the application of alternative trial designs, which may be necessary for successful development of combinational regimens, particularly those incorporating targeted agents.

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Department of Medical OncologyThe Beatson West of Scotland Cancer CentreGlasgowUK
  2. 2.Centre for Oncology and Applied Pharmacology, University of GlasgowCancer Research UK, Beatson LaboratoriesGlasgowScotland

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