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

Abstract

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.

HER2 Amplification or Overexpression in Upper GI Tract and Breast Cancer with Clinical Diagnosis and Treatment

“…In addition, laptinib showed a synergistic effect with trastuzumab in vitro and in vivo to inhibit HER2 amplified human gastric cancer cells and animal model [23]. Clinical phase II trial of lapatinib as first line therapy in patients with advanced or metastatic cancer showed well tolerated, which will be another potential drug to target HER2 receptors [59].…”

Los receptores epidérmicos humanos en el cáncer gástrico: alteraciones moleculares y su papel como diana terapéutica

“…En un ensayo de fase II se encontró que el erlotinib era activo en pacientes con cáncer gastroesofágico, pero no se obtuvo buena respuesta en pacientes con CG 73 (Tabla 2). En un ensayo de fase II se administró una combinación de erlotinib, oxaliplatino, leucovorina y 5-fluorouracilo (5FU) a pacientes sin tratamiento previo con cáncer de esófago avanzado o metastásico y cáncer gastroesofágico; los resultados fueron similares a los reportadas previamente 74 (Tabla 2). El gefitinib fue aprobado por la FDA para el tratamiento del cáncer de pulmón de células no microcíti-cas avanzado 54 .…”

Targeted therapies for advanced and metastatic adenocarcinoma of the gastroesophageal junction: is there something new?

“…One trial suggested that GEJAs were more likely to respond to erlotinib than gastric cancers [32]; in another trial, responses were seen almost exclusively in SCC as compared to AD [33]. A possible explanation is that KRAS and EGFR mutations are uncommon [31][32][33][34][35] and thus not predictive of response to TKI in esophageal cancer. In conclusion, the results were very modest at best for these agents in a metastatic setting.…”

“…Stable disease and RR generally were in the magnitude of 10 %, except in one trial [31]. One trial suggested that GEJAs were more likely to respond to erlotinib than gastric cancers [32]; in another trial, responses were seen almost exclusively in SCC as compared to AD [33].…”