open access: BJC - Functional imaging: what evidence is there for its utility in clinical trials of targeted therapies?

Functional imaging: what evidence is there for its utility in clinical trials of targeted therapies?

"An increasing knowledge about the major pathways dysregulated in cancer has resulted in a large array of targeted pathway inhibitors submitted for phase I trials. Recent figures suggest that <10% of new molecules reach the market primarily because of a lack of demonstrable clinical activity (Kola and Landis, 2004). Other contributing factors include lack of appropriate quantitative imaging methods to guide both preclinical and clinical development. The standard imaging assessment of tumour response relies on size measurements, which, with predominantly cytostatic targeted agents, may not reflect the drug effect. The wide therapeutic index of targeted agents, non-linear relationship between dose and effect and non-mechanism related toxicity may require definition of an optimal biological dose rather than a maximal tolerated dose (MTD). Also, many of these agents may prove to be more effective in combination therapy either with synergistic targeted agents or with chemotherapy and the minimum biologically active dose needs also to be determined. Moreover, because targeted agents are approved for cancer treatment largely based on marginal benefits shown in clinical trials, it means that a large percentage of patients may merely suffer toxicity without therapeutic benefit........