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Bexarotene and erlotinib for aerodigestive tract cancer

Konstantin H Dragnev1, W Jeffrey Petty, Sumit Shah

  • 1Hematology/Oncology Section, Department of Medicine, Norris Cotton Cancer Center, Lebanon, NH, USA.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|November 30, 2005
PubMed
Abstract

Insights

Combining erlotinib and bexarotene shows promise for lung cancer treatment by enhancing growth suppression and improving survival rates. This combination therapy warrants further investigation for advanced aerodigestive tract cancers.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Epidermal growth factor receptor (EGFR) and cyclin D1 are frequently overexpressed in lung cancer.
  • Bexarotene, a rexinoid, has demonstrated in vitro ability to repress both EGFR and cyclin D1 expression.
  • Erlotinib is a known inhibitor of EGFR.

Purpose of the Study:

  • To investigate the potential synergistic effect of combining bexarotene and erlotinib in treating advanced aerodigestive tract cancers.
  • To determine the maximum-tolerated dose (MTD) of the combination therapy.
  • To evaluate the clinical activity and safety profile of the combination.

Main Methods:

  • In vitro studies were conducted to assess the combined effect on cancer cell growth and molecular targets.
  • A Phase I clinical trial was performed involving 24 patients with advanced aerodigestive tract cancers, predominantly non-small-cell lung cancer (NSCLC).
  • The study focused on dose determination and assessment of clinical response and toxicity.

Main Results:

  • In vitro, the combination of erlotinib and bexarotene demonstrated enhanced cancer cell growth suppression and cooperative repression of cyclin D1 expression compared to single agents.
  • The most common toxicities observed in the clinical trial were mild hypertriglyceridemia and skin rash.
  • Five objective responses (four partial, one minor) were noted in NSCLC patients, including smokers and males. Median time to progression was 2.0 months, with a 1-year survival rate of 73.8%.

Conclusions:

  • The recommended Phase II doses for erlotinib and bexarotene combination therapy are 150 mg/d and 400 mg/m2/d, respectively.
  • The combination can be safely administered at these doses without significant added toxicity.
  • The observed overall survival and patient characteristics in responders suggest encouraging results that merit further investigation in larger trials.

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