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A comparative analysis of paediatric dose-finding trials of molecularly targeted agent with adults' trials

Xavier Paoletti1, Birgit Geoerger, François Doz

  • 1Biostatistics department, Institut Curie, Paris, France. xavier.paoletti@curie.net

European Journal of Cancer (Oxford, England : 1990)
|April 2, 2013
PubMed

Insights

Paediatric dose-finding trials for molecularly targeted agents (MTAs) may not always be necessary. Alternative early-phase trials can accelerate drug development in paediatric oncology while managing toxicity.

Area of Science:

  • Paediatric Oncology
  • Clinical Pharmacology
  • Drug Development

Background:

  • Dose-finding phase I trials in children typically follow adult data accumulation.
  • Investigating the role of paediatric dose-finding trials for molecularly targeted agents (MTAs).

Purpose of the Study:

  • To evaluate the necessity and role of paediatric dose-finding trials for MTAs.
  • To compare paediatric recommended phase II doses (RPIID) with adult BSA-adjusted doses.

Main Methods:

  • Reviewed phase I paediatric oncology trials of MTAs approved in adults before June 2012.
  • Compared paediatric RPIID to BSA-adjusted adult doses and analyzed toxicity profiles.

Main Results:

  • 15 MTAs were evaluated in 19 paediatric phase I trials.
  • 70% of trials had paediatric RPIIDs between 90-130% of BSA-adjusted adult doses.
  • 63% of children received suboptimal doses, with similar safety profiles to adults.

Conclusions:

  • Dose-finding studies may not be required for all MTAs in children.
  • Early-phase trials validating adult data (PK, PD, efficacy) while monitoring toxicity can accelerate paediatric drug development, especially for agents with a wide therapeutic index.
Abstract

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