At the right dose: personalised (N-of-1) dosing for precision oncology.

The objective of oncology therapeutics, especially in the age of precision medicine, is to give the right drug(s) to the right patient at the right time. Yet, a major challenge is finding the right dose for each patient. Determining safe and efficacious doses of oncology treatments, especially for novel combination therapies, can be challenging. Moreover, traditionally, dosing cancer drugs is based on giving each patient the same dose (a flat dose) or a dose based on surface area/weight. But patients' ability to tolerate drugs is influenced by additional factors including, but not limited to age, gender, race, comorbidities, organ function, and metabolism. Herein, we present evidence that, in the era of targeted drugs, individualised drug dosing determined by starting at reduced doses and using intrapatient dose escalation can yield safe and effective personalised dosing of novel combinations of approved drugs that have not previously undergone formal phase I trials and can also optimise dosing of tested drug regimens.
Competing Interests: Declaration of Competing Interest Dr. Razelle Kurzrock has received research funding from Boehringer Ingelheim, Debiopharm, Foundation Medicine, Genentech, Grifols, Guardant, Incyte, Konica Minolta, Medimmune, Merck Serono, Omniseq, Pfizer, Sequenom, Takeda, and TopAlliance and from the NCI; as well as consultant and/or speaker fees and/or advisory board/consultant for Actuate Therapeutics, AstraZeneca, Bicara Therapeutics, Inc., Biological Dynamics, Caris, Datar Cancer Genetics, Daiichi, EISAI, EOM Pharmaceuticals, Iylon, LabCorp, Merck, NeoGenomics, Neomed, Pfizer, Prosperdtx, Regeneron, Roche, TD2/Volastra, Turning Point Therapeutics, X-Biotech; has an equity interest in CureMatch Inc. and IDbyDNA; serves on the Board of CureMatch and CureMetrix; and is a cofounder of CureMatch. Dr. Jason Sicklick receives consultant fees from Deciphera, Aadi, and Grand Rounds; serves as a consultant for CureMatch, received speakers fees from Deciphera, La-Hoffman Roche, Foundation Medicine, Merck, QED, and Daiichi Sankyo; and owns stock in Personalis. Dr. Shumei Kato serves as a consultant for Medpace, Foundation Medicine, NeoGenomics, and CureMatch. He receives speaker’s fees from Chugai, Roche/Genentech, and Bayer, and advisory board for Pfizer. He has research funding from ACT Genomics, Sysmex, Konica Minolta, OmniSeq, Personalis, and Function Oncology. Dr. Mina Nikanjam has no conflicts of interest to declare.
(Published by Elsevier Ltd.)