New targeted cancer therapies can have huge benefits over traditional cytotoxics in terms of reducing side effects, according to a new study.
Researchers at the UK Institute of Cancer Research and the Royal Marsden NHS Foundation Trust found that drugs which target specific molecular targets were seven times less likely to cause the most serious side effects than non-specific cancer drugs.
They examined 36 phase I trials enrolling more than 680 patients and found that the overall risk to patients of suffering a grade 4, life-threatening, side effect was 1.9 per cent, compared with 14 per cent found in an analysis of trials from 1991 to 2002 involving older cancer drugs.
Similarly, the risk of a grade 3 severe side effect was 14.1 per cent, compared to 10-36 per cent found across two previous analyses of phase I trials of cytotoxic agents. The mortality rate was also low, at around 0.4 per cent.
“The theory behind targeted drugs is that they should affect only cancer cells that have a specific fault and spare healthy cells, which we hoped would lead to higher rates of efficacy and lower rates of side effects,” said the paper’s lead author Dr Rhoda Molife.
“It’s very pleasing that our study seems to back this up, at least in the context of phase I trials,” she added, noting that recent studies show that patient responses in phase I trials of targeted cancer drugs are around two-fold higher than with older agents.
The team found that the types of side effects experienced by patients were also different between the two groups. While old-style cytotoxics tended to cause haematological or cardiovascular effects, targeted therapies were most commonly linked to gastrointestinal reactions – such as loss of appetite, diarrhoea and vomiting – and fatigue.
The authors also profiled the patients in the studies to see if they could find ways to predict those that would develop adverse reactions.
They found that side effects were more common in those given higher doses of targeted drugs – as might be expected – and also in those who were sicker at enrolment.
The study is published in the August edition of Annals of Oncology.