Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction

Br J Cancer. 2011 Sep 6;105(6):760-5. doi: 10.1038/bjc.2011.280. Epub 2011 Aug 2.


Background: There is increased recognition that cancers of the upper GI tract comprise distinct epidemiological and molecular entities. Erlotinib has shown activity in patients with adenocarcinoma of the oesophagus/gastro-oesophageal junction (GEJ), but not in distal gastric cancer. mFOLFOX6 is one of several active regimens used to treat adenocarcinoma of the Eso/GEJ. This study evaluates the efficacy and safety of mFOLFOX6 and erlotinib in patients with metastatic or advanced Eso/GEJ cancers.

Methods: Patients with previously untreated advanced or metastatic Eso/GEJ adenocarcinoma are treated with oxaliplatin 85 mg m(-2), 5-FU 400 mg m(-2), LV 400 mg m(-2) on day 1, 5-FU 2400 mg m(-2) over 48 h and erlotinib 150 mg PO daily. Treatment was repeated every 14 days. The primary objective was response rate (RR), secondary objectives include toxicity, progression-free survival (PFS), overall survival (OS) and to correlate clinical outcome with expression patterns and molecular alterations in the epidermal growth factor receptor-dependent pathways.

Results: A total of 33 patients were treated and evaluable: there were two complete responses, 15 partial responses for an objective RR of 51.5% (95% CI, 34.5-68.6%). Median PFS was 5.5 months (95% CI, 3.1-7.5 months) and median OS was 11.0 months (95% CI, 8.0-17.4 months). The most common grade 3-4 toxicities were: diarrhoea (24%), nausea/vomiting (11%), skin rash (8%) and peripheral neuropathy (8%). The frequency of alterations was KRAS mutations (8%), EGFR mutations (0%) and HER2 amplification (19%).

Conclusion: In patients with Eso/GEJ adenocarcinoma, mFOLFOX6 and erlotinib is active, has an acceptable toxicity profile and FOLFOX ± erlotinib could be considered for further development.

Publication types

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

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Disease-Free Survival
  • Erlotinib Hydrochloride
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / pathology
  • Esophagogastric Junction* / pathology
  • Female
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use
  • Protein Kinase Inhibitors / administration & dosage*
  • Quinazolines / administration & dosage*


  • Biomarkers, Tumor
  • Organoplatinum Compounds
  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol