Patients were eligible for this study if they fulfilled all of the following criteria: (1) pathologically confirmed unresectable locally advanced, recurrent, or metastatic adenocarcinoma of the pancreas; (2) measurable disease, as defined using version 1.1 of the Response Evaluation Criteria In Solid Tumors (RECIST); (3) age ≥18 years; (4) Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; (5) prior adjuvant chemotherapy without gemcitabine, erlotinib, or S-1 that had been completed >4 weeks before enrollment; (6) more than 4 weeks since completion of prior radiotherapy (measurable lesions are outside the radiation field); (7) adequate hematological, renal, and hepatic functions, as defined using an absolute neutrophil count of ≥1.5 × 109/L, a platelet count of ≥100 × 109/L, serum creatinine levels of ≤1.5 × upper limit of normal or creatinine clearance ≥50 mL/min, serum bilirubin ≤2× UNL, aspartate aminotransferase and alanine aminotransferase levels of ≤2.5×; and, (8) willingness to provide informed consent to participate in this study.

Patients were excluded based on the following criteria: (1) a history of treatment with gemcitabine, erlotinib, or S-1 as adjuvant chemotherapy; (2) contraindication for any drug contained in the chemotherapy regimen; (3) central nervous system metastasis; (4) serious GI bleeding or obvious bowel obstruction; (5) other previous or concurrent malignancies within the last 5 years, with the exception of cured basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix; (6) pregnant or lactating female patients; (7) sexually active and the partner is unwilling to practice contraception during the study; and (8) other clinically significant comorbid conditions, such as an active infection or severe cardiopulmonary dysfunction.

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