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

Ruggero Lasala, Fiorenzo Santoleri, Alessia Romagnoli, Felice Musicco, Alberto Costantini

Research output: Contribution to journalArticlepeer-review


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list of drugs results, we subsequently excluded antineoplastic drugs for hematological diseases, as well as refused and withdrawn drugs.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.

Original languageEnglish
Pages (from-to)697-706
Number of pages10
JournalEuropean Journal of Clinical Pharmacology
Issue number5
Publication statusPublished - May 1 2019
Externally publishedYes


  • Data sharing
  • Dosage adjustment
  • Dose intensity

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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