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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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Enhancing the clinical activity of sorafenib through dose escalation: rationale and current experience

Thomas J Semrad1, David R Gandara, Primo N Lara

  • 1University of California, Davis - Hematology/Oncology, Sacramento, CA, USA.

Therapeutic Advances in Medical Oncology
|July 27, 2011
PubMed

Insights

Sorafenib dose escalation may improve cancer treatment outcomes. However, increased toxicity necessitates careful monitoring within clinical trials for advanced renal cell and hepatocellular carcinoma.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Sorafenib is an oral kinase inhibitor used for advanced renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC).
  • Understanding the sorafenib dose-toxicity relationship is crucial for optimizing treatment strategies.
  • Previous research has explored alternative dosing to enhance clinical activity.

Purpose of the Study:

  • To review the dose-toxicity relationship of sorafenib during early clinical trials.
  • To analyze sorafenib's toxicity profile at recommended doses.
  • To examine evidence for and clinical activity of dose escalation strategies.

Main Methods:

  • Review of Phase I and early Phase II clinical trial data for sorafenib.
  • Analysis of toxicity profiles and dose-response relationships.
  • Evaluation of preliminary data on sorafenib dose escalation.

Main Results:

  • A temporal relationship exists between sorafenib toxicity and dose.
  • Sorafenib exhibits a defined toxicity profile at standard doses.
  • Preliminary evidence suggests potential clinical activity with dose escalation.

Conclusions:

  • Dose escalation of sorafenib may be feasible in select patients.
  • Increased toxicity is a significant concern with higher sorafenib doses.
  • Sorafenib dose escalation should be confined to clinical trial settings.
Keywords:
dose–response relationshipdrugmaximum tolerated dosesorafenibtoxicity

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