Recent developments in adaptive designs for Phase I/II dose-finding studies.
Cancer dose-finding trials aim at assessing the maximum tolerated dose (MTD) of a new treatment or combination. Owing to ethical constraint, they are based on adaptive designs, sequentially allocating patients to increased doses on the basis of previous responses. More recently, the concept of MTD has been extended to the largest concept of most successful or most desirable dose, based on efficacy criterion under toxicity restrictions. The aim of this paper is to present three main approaches proposed to estimate such a dose, in the setting of Phase I/II trials. Two case-studies allow to illustrate these new approaches.
Zohar
Sarah
S
Inserm U717, Département de Biostatistique et Informatique Médicale, Hôpital Saint-Louis, Paris, France.
Chevret
Sylvie
S
D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D006248:Harringtonines / Q000009:adverse effects / Q000627:therapeutic use; D000077863:Homoharringtonine; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy; D011994:Recombinant Proteins; D012107:Research Design
D006248:Harringtonines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000077863:Homoharringtonine