A phase II study of erlotinib in gemcitabine refractory advanced pancreatic cancer

Eur J Cancer. 2014 Jul;50(11):1909-15. doi: 10.1016/j.ejca.2014.04.008. Epub 2014 May 21.


Background: Erlotinib induced skin toxicity has been associated with clinical benefit in several tumour types. This phase II study evaluated the efficacy of erlotinib, dose escalated to rash, in patients with advanced pancreatic cancer previously treated with gemcitabine.

Methods: Erlotinib was given at an initial dose of 150 mg/day, and the dose was escalated by 50mg every 2 weeks (to a maximum of 300 mg/day) until >grade 1 rash or other dose limiting toxicities occurred. Erlotinib pharmacokinetics were performed, and baseline tumour tissue was collected for mutational analysis and epidermal growth factor receptor (EGFR) expression. The primary end-point was the disease control rate (objective response and stable disease >8 weeks).

Results: Fifty-one patients were accrued, and 49 received treatment. Dose-escalation to 200-300 mg of erlotinib was possible in 9/49 (18%) patients. The most common ⩾ grade 3 adverse events included fatigue (6%), rash (4%) and diarrhoea (4%). Thirty-seven patients were evaluable for response, and the best response was stable disease in 12 patients (32% (95% confidence interval (CI) 17-47%)). Disease control was observed in nine patients (24% (95% CI: 10-38%)). Median survival was 3.8 months, and 6 month overall survival rate was 32% (95% CI 19-47%). Mutational analysis and EGFR expression were performed on 29 patients, with 93% having KRAS mutations, none having EGFR mutations, and 86% expressing EGFR. Neither KRAS mutational status nor EGFR expression was associated with survival.

Conclusions: Erlotinib dose escalated to rash was well tolerated but not associated with significant efficacy in non-selected patients with advanced pancreatic cancer.

Trial registration: ClinicalTrials.gov NCT00497224.

Keywords: Erlotinib; Pancreatic cancer; Phase II.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacokinetics
  • Deoxycytidine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Eruptions / etiology
  • Drug Resistance, Neoplasm
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / biosynthesis
  • Erlotinib Hydrochloride
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacokinetics
  • Quinazolines / administration & dosage*
  • Quinazolines / adverse effects
  • Quinazolines / pharmacokinetics


  • Protein Kinase Inhibitors
  • Quinazolines
  • Deoxycytidine
  • gemcitabine
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors

Associated data

  • ClinicalTrials.gov/NCT00497224