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

Eur J Cancer. 2023 Nov:194:113359. doi: 10.1016/j.ejca.2023.113359. Epub 2023 Sep 24.

Abstract

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.

Keywords: Combination therapy; Intrapatient dose escalation; Personalised medicine; Phase 1; Precision medicine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols
  • Dose-Response Relationship, Drug
  • Humans
  • Medical Oncology
  • Neoplasms* / drug therapy
  • Precision Medicine

Substances

  • Antineoplastic Agents