Due to their rarity, only few trials have studied the role of the doxorubicin-streptozotocin (DS) combination in advanced well-differentiated pancreatic endocrine carcinomas (AWDPEC). However, the published results are inconsistent. We reviewed all AWDPEC (5-year period, 45 patients) treated in our institution with the DS combination for: objective response rate (ORR), progression-free survival, overall survival (OS) and toxicity. An ORR of 36% (95% Confidence Interval (CI) 22-49) was obtained, with 16 partial responses (PR). The mean duration of PR was of 19.7 months. Two and 3-year OS rates were 50.2 and 24.4%, respectively. Toxicities were mainly digestive (grade > or =3 vomiting, 13%) and haematological (grade > or =3 neutropenia, 24%). Previous systemic chemotherapy and malignant hepatomegaly were associated with a poorer ORR (P=0.033, P=0.016) and OS (P=0.008, P=0.045). Multivariate analysis demonstrated previous chemotherapy as the only independent predictive-factor for survival (P=0.013). In conclusion, our data confirm the sensitivity of AWDPEC to the DS combination, with an ORR of 36% and a remarkable median response duration of 19.7 months, and suggests that it could be considered as a valid option in first-line therapy.