A Systematic Review of Pediatric Phase I Trials in Oncology: Toxicity and Outcomes in the Era of Targeted Therapies

The oncologist

article

Julia W. Cohen¹  Srivandana Akshintala¹  Eli Kane¹  Helen Gnanapragasam¹  Brigitte C. Widemann¹  Seth M. Steinberg²  Nirali N. Shah¹ 

[1] Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health;Biostatistics and Data Management Section, National Cancer Institute

关键词: Phase I;    Pediatric oncology;    Targeted therapy;    Systematic review;    Toxicity;    Outcome;   

DOI  :  10.1634/theoncologist.2019-0615

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background Pediatric phase I oncology trials have historically focused on safety and toxicity, with objective response rates (ORRs) 25%, of which 11 were targeted trials and 8 were combination cytotoxic trials. Targeted trials demonstrated a lower DLT rate compared with cytotoxic trials (10.6% vs. 14.7%; p = .003) with similar ORRs (15.0% vs. 15.9%; p = .58). Conclusion Pediatric oncology phase I trials in the current treatment era have an acceptable DLT rate and a pooled ORR of 15.3%. A subset of trials with target-specific enrollment or combination cytotoxic therapies showed high response rates, highlighting the importance of these strategies in early phase trials. Implications for Practice Enrollment in phase I oncology trials is crucial for development of novel therapies. This systematic review of phase I pediatric oncology trials provides an assessment of outcomes of phase I trials in children, with a specific focus on the impact of targeted therapies. These data may aid in evaluating the landscape of current phase I options for patients and enable more informed communication regarding risk and benefit of phase I clinical trial participation. The results also suggest that, in the current treatment era, there is a rationale to increase earlier access to targeted therapy trials for this refractory patient population.

【 授权许可】

CC BY|CC BY-NC