Optimizing the doses of cancer drugs after usual dose finding.

Autor:	Strohbehn GW; Veterans Affairs Center for Clinical Management Research, Ann Arbor, MI, USA.; Division of Medical Oncology, Lieutenant Colonel Charles S. Kettles VA Medical Center, Ann Arbor, MI, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.; Institute for Health Policy and Innovation, University of Michigan, Ann Arbor, MI, USA., Stadler WM; Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA., Boonstra PS; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA., Ratain MJ; Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.; Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL, USA.; Center for Personalized Therapeutics, The University of Chicago, Chicago, IL, USA.
Jazyk:	angličtina
Zdroj:	Clinical trials (London, England) [Clin Trials] 2024 Jun; Vol. 21 (3), pp. 340-349. Date of Electronic Publication: 2023 Dec 27.
DOI:	10.1177/17407745231213882
Abstrakt:	Since the middle of the 20th century, oncology's dose-finding paradigm has been oriented toward identifying a drug's maximum tolerated dose, which is then carried forward into phase 2 and 3 trials and clinical practice. For most modern precision medicines, however, maximum tolerated dose is far greater than the minimum dose needed to achieve maximal benefit, leading to unnecessary side effects. Regulatory change may decrease maximum tolerated dose's predominance by enforcing dose optimization of new drugs. Dozens of already approved cancer drugs require re-evaluation, however, introducing a new methodologic and ethical challenge in cancer clinical trials. In this article, we assess the history and current landscape of cancer drug dose finding. We provide a set of strategic priorities for postapproval dose optimization trials of the future. We discuss ethical considerations for postapproval dose optimization trial design and review three major design strategies for these unique trials that would both adhere to ethical standards and benefit patients and funders. We close with a discussion of financial and reporting considerations in the realm of dose optimization. Taken together, we provide a comprehensive, bird's eye view of the postapproval dose optimization trial landscape and offer our thoughts on the next steps required of methodologies and regulatory and funding regimes. Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All authors meet ICMJE criteria for authorship in the presented work. MJR and GWS are Directors of the Optimal Cancer Care Alliance, a 501(c)3 organization. GWS is an employee of the US Federal Government; the views expressed in this article do not reflect the views of the US Federal Government and are his personal views. GWS and MJR are co-inventors of intellectual property covering the use of low-dose tocilizumab in treating viral infections, outside of the submitted work. GWS and PSB are co-inventors of a filed provisional patent held by the University of Michigan and the US Department of Veterans Affairs covering methods of postapproval dose optimization. No royalties or licensing fees are generated by either patent. GWS reports consulting fees from VIVIO Health.
Databáze:	MEDLINE
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