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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

Association of creatine kinase and skin toxicity in phase I trials of anticancer agents

V Moreno Garcia1, P Thavasu, M Blanco Codesido

  • 1Drug Development Unit, Division of Cancer Therapeutics and Division of Clinical Studies, The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, UK.

British Journal of Cancer
|October 27, 2012
PubMed
Abstract

Insights

Plasma creatine kinase (CK) elevation is linked to skin rash in patients receiving novel cancer therapies. Further research into CK isoforms is needed for improved adverse event reporting in clinical trials.

Area of Science:

  • Oncology
  • Clinical Pharmacology
  • Dermatology

Background:

  • Investigated the association between skin rash and plasma creatine kinase (CK) levels in oncology phase I trials.
  • Examined data from 295 patients across 25 phase I trials involving novel anticancer agents.

Purpose of the Study:

  • To determine the relationship between skin rash severity and plasma CK levels in cancer patients undergoing early-phase trials.
  • To explore the potential of CK as a biomarker for treatment-related skin toxicities.

Main Methods:

  • Analyzed CK measurements from 278 patients in phase I trials targeting various pathways (EGFR, m-TOR, VEGFR, etc.).
  • Correlated plasma CK levels with the grade of skin rash (Grade 0, 1, 2/3).
  • Assessed CK level changes after rash resolution and conducted in vitro studies on keratinocytes exposed to targeted inhibitors.

Main Results:

  • Patients with Grade 2/3 rash exhibited significantly higher plasma CK levels (median 249 U/L) compared to those with Grade 1 (81 U/L) or no rash (55 U/L).
  • A significant reduction in CK levels was observed after rash resolution (264.2 vs 100.1).
  • In vitro, EGFR, MEK, and PI3Kinase/m-TOR inhibitors increased CK-brain expression in keratinocytes.

Conclusions:

  • Elevated plasma CK is associated with skin rash induced by novel anticancer drugs.
  • Further investigation into specific CK isoforms is warranted to refine adverse event reporting in oncology phase I trials.

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