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Trends, Outcomes, and Characteristics of Pediatric Oncology Phase I and II Studies: A Systematic Review

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Abstract

Introduction

Tremendous improvement in the overall survival of pediatric cancer patients has occurred over the past 40 years, but this may be slowing down. Continued progress depends on the development of new drugs and their prompt evaluation in clinical trials.

Objective

Because of a perceived increase due to a greater number of drugs in development in adult oncology clinical trials, we examined recent trends and outcomes of early-phase clinical trials conducted in pediatric oncology.

Methods

We conducted a literature review using PubMed and examined articles between January 2005 and December 2010. Inclusion criteria consisted of (1) reports published in English, (2) trials conducted exclusively in the United States or Canada, and (3) enrollment of patients under the age of 22 years. Excluded were trials evaluating radiation therapy, stem cell transplantation, supportive care, and therapies for non-oncologic diseases.

Results

We identified 75 early-phase trials, 64 drug and 11 immunotherapy, involving 2,286 patients below the age of 22 years. Complete or partial responses were observed for 5 % (phase I) and 19 % (phase II) of patients. Study-associated deaths occurred in 5 % (phase I) and 20 % (phase II) of patients. Progressive disease accounted for the vast majority of these deaths, followed by infection. Only two of the 43 phase I and none of the 11 phase II studies were sponsored solely by industry. Time to complete enrollment was 29 ± 14 and 49 ± 20 months for pediatric phase I and II drug studies, respectively. Pediatric early-phase drug trials demonstrated efficacy with low toxic death rates. Pediatric trials, including immunotherapy trials, showed less industrial support and longer phase II enrollment times than adult trials. Between 1990 and 2010, adult trials increased linearly, while growth in pediatric trials was flat. Only three of the drugs approved by the FDA between 2000 and 2010 were also approved for pediatrics.

Conclusions

Published pediatric oncology early-phase trials have not shown the same linear increase as adult trials. We have identified differences in sponsorship and longer enrollment times for phase II trials.

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Acknowledgments

The authors declare no competing financial interests. The authors declare no conflict of interest. H.L., J.B., and S.J.C. contributed to the conception and design of the study, the writing and analysis of results, and the final approval of the manuscript. No sources of funding were received for the conduct of the study or the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Pediatrics, Lurie Children’s Hospital of Chicago, Chicago, USA

    Hannah Lu & Seth J. Corey

  2. Lurie 5-107, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 303 E. Superior Street, Chicago, IL, 60611, USA

    Hannah Lu & Seth J. Corey

  3. Department of Pediatrics and the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    Julie Blatt

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  1. Hannah Lu
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  2. Julie Blatt
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  3. Seth J. Corey
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Correspondence to Seth J. Corey.

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Lu, H., Blatt, J. & Corey, S.J. Trends, Outcomes, and Characteristics of Pediatric Oncology Phase I and II Studies: A Systematic Review. Pharm Med 27, 235–244 (2013). https://doi.org/10.1007/s40290-013-0021-7

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  • DOI: https://doi.org/10.1007/s40290-013-0021-7

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