Skip to Main content Skip to Navigation
Journal articles

Optimal biological dose: a systematic review in cancer phase I clinical trials

Abstract : Background: Classical phase 1 dose-finding designs based on a single toxicity endpoint to assess the maximum tolerated dose were initially developed in the context of cytotoxic drugs. With the emergence of molecular targeted agents and immunotherapies, the concept of optimal biological dose (OBD) was subsequently introduced to account for efficacy in addition to toxicity. The objective was therefore to provide an overview of published phase 1 cancer clinical trials relying on the concept of OBD. Methods: We performed a systematic review through a computerized search of the MEDLINE database to identify early phase cancer clinical trials that relied on OBD. Relevant publications were selected based on a two-step process by two independent readers. Relevant information (phase, type of therapeutic agents, objectives, endpoints and dose-finding design) were collected. Results: We retrieved 37 articles. OBD was clearly mentioned as a trial objective (primary or secondary) for 22 articles and was traditionally defined as the smallest dose maximizing an efficacy criterion such as biological target: biological response, immune cells count for immunotherapies, or biological cell count for targeted therapies. Most trials considered a binary toxicity endpoint defined in terms of the proportion of patients who experienced a doselimiting toxicity. Only two articles relied on an adaptive dose escalation design. Conclusions: In practice, OBD should be a primary objective for the assessment of the recommended phase 2 dose (RP2D) for a targeted therapy or immunotherapy phase I cancer trial. Dose escalation designs have to be adapted accordingly to account for both efficacy and toxicity.
Document type :
Journal articles
Complete list of metadata

https://www.hal.inserm.fr/inserm-03217931
Contributor : Odile Malbec <>
Submitted on : Wednesday, May 5, 2021 - 11:12:50 AM
Last modification on : Thursday, May 6, 2021 - 3:12:49 AM

File

s12885-021-07782-z.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

J Fraisse, D Dinart, D Tosi, C Bellera, C Mollevi. Optimal biological dose: a systematic review in cancer phase I clinical trials. BMC Cancer, BioMed Central, 2021, 21 (1), pp.60. ⟨10.1186/s12885-021-07782-z⟩. ⟨inserm-03217931⟩

Share

Metrics

Record views

21

Files downloads

19