© 2016 S. Karger AG, Basel.Background/Methods: Thirty patients with advanced progressive grade 1 or 2 pancreatic neuroendocrine tumors (pNETs), treated on a prospective phase II single-center study, were followed up for up to 4 years after 4 cycles of 7.9 GBq 177Lu-octreotate combined with chemotherapy. Each 8-week cycle of treatment combined radiopeptide therapy with 14 days of capecitabine at 1,500 mg/m2 and 5 days of temozolomide at 200 mg/m2. Results: The overall response rate was 80% (95% CI 66-93), and there was complete remission in 13% (95% CI 4-30) and partial response in 70% (95% CI 52-83) of the cases. No patient manifested progressive disease on treatment. Median progression-free survival was 48 months. Median overall survival had not been reached at a median follow-up of 33 months. No patient was lost to follow-up, all but 1 received 4 cycles of outpatient therapy, and all were evaluated for response and toxicity. No one required hospital admission. The treatment was well tolerated, and no serious dose-limiting toxicities were seen. The commonest toxicity was transient nausea of grade 2 (33%) or 3 (7%). Hematological toxicity was limited to grade 3 thrombocytopenia (10%) and anemia (10%). There were no grade 4 adverse events, and no renal functional impairment was evident. Conclusion: Combined 177Lu-octreotate-capecitabine-temozolomide radiopeptide chemotherapy is a well-tolerated, highly effective outpatient regimen for control of advanced progressive pNETs, achieving a durable objective response.