Overall, the response rate among all trials was 10.29% (95% CI 8.33 to 12.25) but the rate was significantly different for solid tumors (3.17, 95% CI 2.62 to 3.72) compared to hematological malignancies (27.90, 95% CI 20.53 to 35.27). The overall rate of fatal grade 5 adverse events was 2.09% (95% CI 1.45 to 2.72) and there was an average of 1.32 grade 3 and 4 drug-related adverse events per person. On the whole, adverse event and response rates were similar to those seen in adult phase I cancer trials.
The authors note several limitations to their study, including heterogeneity in the types of cancer and treatment in the included trials, reliance on published data only, and low-quality or incomplete reporting of some trial outcomes.
"Our data, coupled with careful ethical analysis, provide an empirical basis for further discussions about the therapeutic status of phase I trials in children," the authors say. "In particular, they provide evidence for refining risk/benefit in phase I trials and identifying those studies that present greater challenges for meeting standards of acceptable risk in children."
Waligora M, Bala MM, Koperny M, Wasylewski MT, Strzebonska K, Jaeschke RR, Wozniak A, Piasecki J, Sliwka A, Mitus JW, Polak M, Nowis D, Fergusson D, Kimmelman J.
Risk and surrogate benefit for pediatric Phase I trials in oncology: A systematic review with meta-analysis.
PLoS Med. 2018 Feb 20;15(2):e1002505. doi: 10.1371/journal.pmed.1002505.