Efficacy and Safety of Fixed-Dose-Rate Infusions of Gemcitabine Plus Erlotinib for Advanced Pancreatic Cancer

Purpose : To evaluate the efficacy and safety of fixed-dose-rate infusions of gemcitabine in combination with erlotinib for advanced pancreatic cancer. Methods/Patients : Patients with locally advanced (LAPC) or metastatic pancreatic cancer (MPC) without previous treatment for the advanced disease and Eastern Cooperative Oncology Group performance status ≤2 received 1500 mg/m 2 of gemcitabine in 150-minute infusions (10 mg/m 2 /minute) on days 1, 8 and 15 in 4-week cycles combined with 100 mg/day of oral erlotinib. The primary endpoint was overall survival (OS). Results : Sixty-two evaluable patients were enrolled (LAPC, n=16; MPC, n=46). Median OS was 10.0 (95% CI, 7.1-13.0) months. OS was longer in patients with LAPC (p=0.019), females (p=0.010) and patients not receiving opioids (p=0.027). A trend towards longer OS was shown in patients with grade ≥2 rash (p=0.078). In multivariate analysis, only gender remained statistically significant (p=0.01). Median PFS was 4.9 (95% CI, 3.1-6.8) months, which was longer in patients with LAPC (p=0.004) and females (p=0.013). Overall response rate was 12.9% (95% CI, 4.7-21.3), with eight patients achieving partial response, and tumour growth control rate was 67.7% (95% CI, 79.3-56.1). The main grade 3/4 adverse events were neutropenia (40.3%), asthenia (22.6%), anaemia (19.4%), thrombocytopenia (17.7%) and infections (14.5%). Three patients died due to septic shock, cholangitis or pulmonary embolism. Conclusions : The combination of fixed-dose-rate infusions of gemcitabine and erlotinib represents a feasible and active regimen for advanced pancreatic cancer with a manageable safety profile.