Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal cancer

Br J Cancer. 2006 Apr 24;94(8):1136-43. doi: 10.1038/sj.bjc.6603055.


Erlotinib (Tarceva, OSI-774), a potent epidermal growth factor receptor tyrosine kinase inhibitor (EGFR), was evaluated in a phase II study to assess its activity in patients with metastatic colorectal cancer. In all, 38 patients with metastatic colorectal cancer were treated with erlotinib at a continuous daily oral dose of 150 mg. Radiological evaluation was carried out every 8 weeks and tumour biopsies were performed before treatment and on day 8. Of 31 evaluable patients, 19 (61%) had progressive disease and 12 (39%) had stable disease (s.d.). The median time to progression for those patients having s.d. was 123 days (range 108-329 days). The most common adverse events were rash in 34 patients and diarrhoea in 23 patients. Correlative studies were conducted to investigate the effect of erlotinib on downstream signalling. Tumour tissue correlations were based on usable tissue from eight match paired tumour samples pre- and on therapy, and showed a statistically significant decrease in the median intensity of both pEGFR (P=0.008) and phospho-extracellular signal-regulated kinase (ERK) (P=0.008) a week after commencement of treatment. No other statistically significant change in tumour markers was observed. Erlotinib was well tolerated with the most common toxicities being rash and diarrhoea. More than one-third of evaluable patients had s.d. for a minimum of 8 weeks. Correlative studies showed a reduction in phosphorylated EGFR and ERK in tumour tissue post-treatment.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Disease Progression
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Quinazolines / adverse effects
  • Quinazolines / pharmacokinetics
  • Quinazolines / therapeutic use*
  • Recurrence
  • Risk Factors
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Survival Rate
  • Treatment Outcome


  • Antineoplastic Agents
  • Quinazolines
  • Erlotinib Hydrochloride
  • ErbB Receptors