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European Journal of Clinical Pharmacology

, Volume 75, Issue 5, pp 697–706 | Cite as

Dosage adjustments in pivotal clinical trials with oral targeted therapies in solid tumors conducted in Europe

  • Ruggero LasalaEmail author
  • Fiorenzo Santoleri
  • Alessia Romagnoli
  • Felice Musicco
  • Alberto Costantini
Pharmacoepidemiology and Prescription
  • 96 Downloads

Abstract

Purpose

The aim of this study was to evaluate in what measure is dosage adjustment particularly prevalent in pivotal clinical trials of oral targeted therapy drugs approved by the European Medicine Agency as of July 31, 2018, for the treatment of solid tumors.

Methods

We performed a search on the official EMA site on human medicines, using as Keyword Search the ATC Code L01X (other antineoplastic agents); from the list of drugs results, we subsequently excluded antineoplastic drugs for hematological diseases, as well as refused and withdrawn drugs. For all analyzed drugs, we recorded full dosages, dose adjustments with relative reduction percentage, reason for the adjustments, number of patients included in the trial, percentage of patients who reduced their dosage or temporarily discontinued therapy, cause of dose reduction, and presence or absence of reference to a clinical outcome in patients who reduced their dose or discontinued therapy.

Results

We considered 74 pivotal trials on 29 target therapies, of which 56 (76%) provide information on dosage reduction, 41 (55%) on therapy suspension, and 29 (39%) on the dose taken by the sample. Trials that provide information on dosage adjustment include reduction and suspension data widely used to manage side effects; they concern, respectively, 32 and 44% of the samples considered. No trial results take account of the possible role of adjustment in clinical outcomes.

Conclusion

It would be advisable for pivotal clinical trials to give more relevance to dose management, which is a widely used tool for the management of adverse events in clinical practice. To date, such information is lacking.

Keywords

Dose intensity Data sharing Dosage adjustment 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ruggero Lasala
    • 1
    Email author
  • Fiorenzo Santoleri
    • 2
  • Alessia Romagnoli
    • 2
  • Felice Musicco
    • 3
  • Alberto Costantini
    • 2
  1. 1.Hospital Pharmacy ASL BariBariItaly
  2. 2.Hospital Pharmacy, Pescara General HospitalPescaraItaly
  3. 3.Hospital Pharmacy, IFO Regina Elena San GallicanoRomeItaly

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