A phase II trial of erlotinib in combination with gemcitabine and capecitabine in previously untreated metastatic/recurrent pancreatic cancer: combined analysis with translational research

Invest New Drugs. 2012 Jun;30(3):1164-74. doi: 10.1007/s10637-011-9651-3. Epub 2011 Mar 15.

Abstract

Background: To confirm the efficacy and toxicity of Erlotinib in combination with Gemcitabine and Capecitabine when used as a first-line therapy in metastatic/recurrent pancreatic cancer (PC).

Methods: Locally advanced PC was excluded. Erlotinib was given at a dose of 100 mg daily from D1 to D28. 1000 mg/m(2) of gemcitabine was given on D1,8,15 and 1660 mg/m(2)/day of capecitabine was given from D1 to 21, repeated every 4 weeks. Response was assessed every 8 weeks.

Results: A total of 47 patients were enrolled. Response rate and disease control rate was 32.6% (95% CI, 18.6-46.6%) and 83.7% (95% CI, 72.7-94.7%) respectively. The PFS was 6.5 months (95% CI, 3.4-9.7) and OS was 12.0 months (95% CI, 8.6-15.9). The Gr 3/4 toxicities were: neutropenia (6.8%), thrombocytopenia (3.2%), anemia (1.6%). nausea (1.6%), vomiting (1.6%), anorexia (5.3%), rash (2.4%). The EGFR expression was associated with shorter OS and ERCC2 expression was associated with longer PFS and OS. PFS and OS were not different according to K-RAS mutation or polymorphism of RRM1 and CDA.

Conclusions: Erlotinib, gemcitabine and capecitabine combination showed promising efficacy and good tolerability in metastatic PC. This efficacy was observed irrespective of K-RAS mutation, and EGFR expression was poor prognostic factor for OS.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Capecitabine
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Gemcitabine
  • Gene Amplification
  • Genes, ras / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Polymorphism, Single Nucleotide
  • Quinazolines / administration & dosage
  • Treatment Outcome
  • Xeroderma Pigmentosum Group D Protein / metabolism*

Substances

  • Biomarkers, Tumor
  • Quinazolines
  • Deoxycytidine
  • Capecitabine
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • Fluorouracil
  • Gemcitabine