Phase II study of gefitinib adaptive dose escalation to skin toxicity in recurrent or metastatic squamous cell carcinoma of the head and neck

Oral Oncol. 2012 Sep;48(9):887-92. doi: 10.1016/j.oraloncology.2012.03.020. Epub 2012 Apr 17.

Abstract

Background: Gefitinib has activity in patients with advanced squamous cell carcinoma of the head and neck (SCCHN) and skin toxicity has been postulated to be a predictor of response and improved outcome.

Methods: This open-label, multi-institution, phase II study evaluated the activity of gefitinib at individually escalated doses up to 750 mg to achieve the skin toxicity grade ≥2.

Results: Forty four patients were enrolled. Only twenty-three (52%) experienced skin rash grade ≥2. Of 44 patients, partial responses were noted in 3 (7%), stable disease in 8 (18%) and progressive disease in 33 patients. Median progression-free survival was 1.9 months (95% CI 1.6-2.2) and median overall survival was 5.1 months (95% CI 2.4-7.8). Grade of skin rash was not associated with response rate (p=0.169) nor tumor control rate (p=0.284); however, higher gefitinib trough levels were associated with disease control. Of the 11 tissue samples analyzed for EGFR gene copy by FISH, 7 were EGFR FISH positive, but this was not associated with improved tumor control or survival.

Conclusions: Gefitinib has clinical activity as monotherapy in SCCHN. Dose escalation of gefitinib is feasible and may increase skin toxicity, but our data do not support increased activity.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Gefitinib
  • Head and Neck Neoplasms / drug therapy*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Quinazolines / adverse effects
  • Quinazolines / pharmacokinetics
  • Quinazolines / therapeutic use*
  • Skin / drug effects*

Substances

  • Antineoplastic Agents
  • Quinazolines
  • Gefitinib