Enhancing the clinical activity of sorafenib through dose escalation: Rationale and current experience

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Abstract

Sorafenib is an oral multitargeted tyrosine and serine/threonine kinase inhibitor approved for the treatment of advanced renal cell and hepatocellular carcinoma. An understanding of its dose-toxicity relationship has paved the way for trials seeking to enhance its clinical activity through the exploration of alternative dosing strategies. In this article, we review the dose-toxicity relationship of sorafenib observed during its phase I and early phase II testing, explore its toxicity profile at the recommended dose and schedule, discuss the evidence for dose escalation to higher levels, and examine the preliminary evidence for clinical activity of this strategy. Owing to a temporal relationship between toxicity and dose, it may be possible in select patients to escalate sorafenib to doses beyond those currently employed. However, because of the potential for increased toxicity, sorafenib dose escalation should currently be performed only in the context of a clinical trial.

Original languageEnglish (US)
Pages (from-to)95-100
Number of pages6
JournalTherapeutic Advances in Medical Oncology
Volume3
Issue number2
DOIs
StatePublished - Mar 2011

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Keywords

  • Dose-response relationship
  • Drug
  • Maximum tolerated dose
  • Sorafenib
  • Toxicity

ASJC Scopus subject areas

  • Oncology

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