4607 Background: To confirm the efficacy and toxicity of erlotinib (E) in combination with gemcitabine (G) and capecitabine (C) when used as a first-line therapy in patients (pts) with metastatic/recurrent pancreatic cancer Methods: Pts with advanced pancreatic adenocarcinoma, with measurable lesion were eligible for the study. Other eligibility criteria included: no previous palliative chemotherapy, Karnofsky performance status (PS)≥50, adequate organ function. Locally advanced pancreatic cancer was excluded. E was given at a dose of 100mg daily from D1 to D28. G was given at a dose of 1000mg/m2 on D1,8,15 and C was given at a dose of 1660mg/m2/d from D1 to 21, repeated every 4 weeks. Response was assessed every 8 weeks. Tumor tissue and blood sample was analyzed for the translational research. Results: A total of 47 pts were enrolled between Feb 2007 and Feb 2008. (median age: 58 y, Karnofsky PS100/90/80/70/60 (6/26/9/5/1)). Forty three pts were evaluable for response. Partial responses were achieved in 14 patients, resulting in response rate of 32.6%. Twenty two pts (51.2%) had stable disease. Overall disease control rate was 83.7%. The PFS was 6.5 months (95% CI, 3.4–9.7) and the overall survival was 12.0 months (95% CI, 8.6–15.9). The Gr 3/4 hematologic toxicities were: neutropenia (6.8%), thrombocytopenia (3.2%), anemia (1.6%). The major Gr 3/4 nonhematologic toxicities were: nausea (1.6%), vomiting (1.6%), anorexia (5.3%), rash (0.5%). EGFR, pEGFR, TS, TP, DPD was overexpressed in 77.4%, 17.1%, 82.4%, 53.6% and 61.3% of tumor tissues respectively. EGFR amplification was not detected. Among these, the EGFR expression was significantly associated with shorter PFS and OS (p=0.029, p=0.005 respectively). K-RAS mutation was detected in 47.5%. PFS and OS were not different according to K-RAS mutation. RRM1 2455G>A, RRM1 2464G>A, CDA 79A>C, CDA 435C>T polymorphism did not influence on the PFS and OS. Conclusions: Erlotinib in combination with gemcitabine and capecitabine showed promising efficacy and good tolerability in metastatic pancreatic cancer. This efficacy was observed irrespective of K-RAS mutation, and the EGFR expression was poor prognostic factor for PFS and OS. No significant financial relationships to disclose.
Perspectives of Translational Research for pancreatic Cancer
