Design and Analysis of Phase I Trials in Clinical Oncology

  • Axel Benner
  • Lutz Edler
  • Gernot Hartung


In oncology the Phase I trial is the first occasion to treat cancer patients experimentally with a new drug with the aim of determining the drug treatment’s toxic properties, characterizing its dose-limiting toxicity (DLT), and estimating a maximum tolerable dose (MTD) as a benchmark dose for further clinical trials. Phase I trials are usually accompanied by an elaborate clinical pharmacology and the determination of individual pharmacokinetic parameters. Additionally, there is high interest in screening the drug for early signs of antitumor activity (Von Hoff et al., 1984). At this stage of drug development, a safe and efficacious dose in humans is unknown and information is available only from pre-clinical in vitro and in vivo studies. Therefore, patients are treated successively and in small groups, beginning at a low dose very likely to be safe (starting dose), and escalating progressively to higher doses until drug-related toxicity manifests and reaches DLT. Doses which induce a predetermined frequency of DLT among the patients treated, define the MTD (Bodey and Legha, 1987).


Dose Level Maximum Tolerable Dose Toxicity Data Common Toxicity Criterion Population Pharmacokinetic Analysis 
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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Axel Benner
    • 1
  • Lutz Edler
    • 1
  • Gernot Hartung
    • 2
  1. 1.Biostatistics UnitGerman Cancer Research CenterHeidelbergGermany
  2. 2.Oncological CenterMannheim Medical SchoolHeidelbergGermany

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