Lower risk of serious side-effects in trials of new targeted drugs

Patients in early clinical trials of new-style targeted cancer therapies appear to have a much lower risk of the most serious side-effects than with traditional chemotherapy, according to a new analysis.

Researchers in the ICR and The Royal Marsden’s joint Drug Development Unit analysed data from 36 Phase I trials of molecularly targeted drugs carried out between January 2005 and December 2009. The study included 687 patients with a range of cancer types.

The study, led by Dr Rhoda Molife, a medical oncologist and senior investigator in Phase I clinical trials in the Drug Development Unit, found the overall risk to patients of suffering a life-threatening side-effect was around seven times less than for traditional cytotoxic agents.

The risk of a Grade 4, life-threatening, side-effect in this study was 1.9 per cent, compared with 14 per cent found in an analysis of trials from 1991 to 2002. The risk of a Grade 3, severe, side-effect in this study was 14.1 per cent, compared to 10-36 per cent found across two previous analyses of Phase I trials of cytotoxic agents.

Recent studies have shown that patient response rates in Phase I trials of new-generation targeted drugs are approximately two-fold higher than for old-style drugs. But until now, the risk of side-effects to patients taking part in early stage trials of new-style drugs has been unclear.

The team also found characteristics that put patients at higher risk of toxicity, including if they were sicker when joining the trial or were given a higher dose than that which the trial later found to be optimal. The findings should help guide researchers in selecting patients for trials and improving trial design.

The results were published in the journal Annals of Oncology.