Modern Dose-Finding Designs for Cancer Phase I Trials: Drug Combinations and Molecularly Targeted Agents

  • Akihiro Hirakawa
  • Hiroyuki Sato
  • Takashi Daimon
  • Shigeyuki Matsui

Part of the SpringerBriefs in Statistics book series (BRIEFSSTATIST)

Also part of the JSS Research Series in Statistics book sub series (JSSRES)

Table of contents

  1. Front Matter
    Pages i-xiii
  2. Akihiro Hirakawa, Hiroyuki Sato, Takashi Daimon, Shigeyuki Matsui
    Pages 1-7
  3. Akihiro Hirakawa, Hiroyuki Sato, Takashi Daimon, Shigeyuki Matsui
    Pages 9-40
  4. Akihiro Hirakawa, Hiroyuki Sato, Takashi Daimon, Shigeyuki Matsui
    Pages 41-58
  5. Akihiro Hirakawa, Hiroyuki Sato, Takashi Daimon, Shigeyuki Matsui
    Pages 59-80
  6. Akihiro Hirakawa, Hiroyuki Sato, Takashi Daimon, Shigeyuki Matsui
    Pages 81-89

About this book


This book deals with advanced methods for adaptive phase I dose-finding clinical trials for combination of two agents and molecularly targeted agents (MTAs) in oncology. It provides not only methodological aspects of the dose-finding methods, but also software implementations and practical considerations in applying these complex methods to real cancer clinical trials. Thus, the book aims to furnish researchers in biostatistics and statistical science with a good summary of recent developments of adaptive dose-finding methods as well as providing practitioners in biostatistics and clinical investigators with advanced materials for designing, conducting, monitoring, and analyzing adaptive dose-finding trials. The topics in the book are mainly related to cancer clinical trials, but many of those topics are potentially applicable or can be extended to trials for other diseases. The focus is mainly on model-based dose-finding methods for two kinds of phase I trials. One is clinical trials with combinations of two agents. Development of dose-finding methods for two-agent combination trials requires reasonable models that can adequately capture joint toxicity probabilities for two agents, taking into consideration possible interactions of the two agents on toxicity probability such as synergistic or antagonistic effects. Another is clinical trials for evaluating both efficacy and toxicity outcomes in single- and two-agent combination trials. These methods are often applied to the phase I trials including MTAs because the toxicity and efficacy for a MTA does not monotonically increase with dose, but the efficacy often increases initially with the dose and then plateaus. Successful software implementations for several dose-finding methods are introduced in the book, and their operating characteristics in practice are discussed. Recent advance of the adaptive dose-finding methods in drug developments are also provided.


Adaptive Design Cancer Dose Finding Phase I Phase I/II

Authors and affiliations

  • Akihiro Hirakawa
    • 1
  • Hiroyuki Sato
    • 2
  • Takashi Daimon
    • 3
  • Shigeyuki Matsui
    • 4
  1. 1.Department of Biostatistics and Bioinformatics, Graduate School of MedicineThe University of TokyoTokyoJapan
  2. 2.Pharmaceuticals and Medical Devices AgencyTokyoJapan
  3. 3.Division of BiostatisticsHyogo College of Medicine Division of BiostatisticsHyogoJapan
  4. 4.Depart Biostatis, Graduate Scl MedNagoya University Depart Biostatis, Graduate Scl MedNagoyaJapan

Bibliographic information

  • DOI
  • Copyright Information The Author(s) 2018
  • Publisher Name Springer, Tokyo
  • eBook Packages Mathematics and Statistics
  • Print ISBN 978-4-431-55572-8
  • Online ISBN 978-4-431-55573-5
  • Series Print ISSN 2191-544X
  • Series Online ISSN 2191-5458
  • Buy this book on publisher's site
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