Phase i trials involving radiation therapy, quantifying the risks

Introduction Over one third of cancer patients receive radiation therapy (RT) at some point. Our purpose was to quantify the risks to patients associated with enrolment onto RT-based phase I trials. Methods All phase I and phase I/II clinical trials involving RT published in English between 2001 and 2010 were identified via a PubMed search. For pragmatic reasons, we focused on trials from 2001, 2005 and 2009. For each trial we calculated a 'toxicity ratio' equal to the number of grade 3/4/5 toxic events divided by the number of patients in the trial. Linear regression was used to determine which variables were associated with higher toxicity ratios. Results There were a total of 33 treatment-related deaths, and 1812 acute grade 3/4 toxicities among the 2994 subjects in 98 trials. The median toxicity ratio over 98 trials was 0.46 (95% confidence interval (CI) 0.34 to 0.58). Multivariate regression analysis showed that toxicity ratios were significantly higher in trials with chemotherapy (P = 0.002) and in trials for cancers of the head-and-neck (P < 0.001). The median toxicity ratio in chemotherapy trials was 0.60 (95% CI: 0.48 to 0.72) compared with trials without chemotherapy 0.08 (95% CI: 0.03 to 0.13). Conclusions Although the risk of grade 5 toxicity is low, the risk of major toxicity is significant in phase I RT trials. These values are comparable to published risk estimates for phase I non-RT trials.