A comparison of safety and efficacy of cytotoxic versus molecularly targeted drugs in pediatric phase I solid tumor oncology trials
Until now there was no direct comparison of toxicity and efficacy data between cytotoxic and targeted agents in paediatric oncology clinical trials. This systematic review collected safety and response data for classes of anticancer agents based on a review of past clinical trial results to help guide future phase I/II clinical trial designs for novel targeted drugs.
Systematic review of pediatric phase I recurrent/refractory solid tumor trials. Published reports were evaluated for patient characteristics, toxicity information, and response rates. 143 phase I paediatric solid tumor clinical trials were identified, enrolling 3,896 children. 61 trials investigated 53 targeted drugs and 82 trials evaluated 48 cytotoxic agents.
Cytotoxic drugs had a higher objective response rate but also higher dose limiting toxicities and hematologic toxicities. There was no difference between cytotoxic and targeted agents in non-hematologic toxicities and progression free survival.
The biggest limitation is that meta-analyses of small underpowered trials are likely to result in false positives and negatives. This was a high degree of heterogeneity amongst the included articles. For example, there was no universally accepted method of reporting toxicities.