Background Both everolimus and temozolomide are associated with single-agent activity in patients with pancreatic neuroendocrine tumor (NET). We performed a phase I/II study to evaluate the safety and efficacy of temozolomide in combination with everolimus in patients with advanced pancreatic NET. Methods Patients were treated with temozolomide 150 mg/m2 per day on days 1–7 and days 15–21 in combination with everolimus daily in each 28-day cycle. In cohort 1, temozolomide was administered together with everolimus 5 mg daily. Following demonstration of safety in this cohort, subsequent patients in cohort 2 were treated with temozolomide with everolimus 10 mg daily. The duration of temozolomide treatment was limited to 6 months. Patients were followed for toxicity, radiologic and biochemical response, and survival. Results A total of 43 patients were enrolled, including 7 in cohort 1 and 36 in cohort 2. Treatment was associated with known toxicities of each drug; no synergistic toxicities were observed. Among 40 evaluable patients, 16 (40%) experienced a partial response. The median progression-free survival duration was 15.4 months. Median overall survival was not reached. Conclusions Temozolomide and everolimus can be safely administered together in patients with advanced pancreatic NET, and the combination is associated with encouraging antitumor activity. Future studies evaluating the efficacy of combination therapy compared to treatment with either agent alone are warranted.

A standardised, effective systemic therapy for metastatic neuroendocrine tumours (NETs) has not been established to date. We reviewed the management of 15 patients with inoperable, metastatic NET treated systematically with a combination chemotherapy regimen of infusional 5-fluorouracil, folinic acid and streptozocin. Overall objective response rate was 53% and tolerability was excellent.