Streptozocin-based chemotherapy in patients with advanced pancreatic neuroendocrine tumors.

Abstract

295 Background: The role of systemic chemotherapy for advanced pancreatic neuroendocrine tumours (pNETs) is controversially discussed. Objective response rates (RR) with streptozocin(STZ)-based chemotherapy range between 6% and 69%. Novel targeted drugs have recently been approved, however sequence of treatment remains unclear. We aimed to evaluate efficacy of STZ+5-FU chemotherapy in a large pNET cohort. Methods: Clinical data of 95 patients (pts) with advanced pNET who had been treated with STZ+5-FU between Aug 1998 and Sept 2013 were analyzed retrospectively. RR, time to tumour progression (TTP) and overall survival (OS) were assessed. Assessment of RR was judged by tumour board involving an experienced radiologist (TD). Results: Median age at start of chemotherapy was 60 years (range 32-80). 74 pts (77.9%) had non-functional pNETs. In 52 pts (54.7%) STZ+5-FU was 1st line systemic therapy. 11.6% had G1, 78.9% G2 and 6.3% G3 tumours. Baseline progression was evident in 75.8% of cases. Mean number of therapy cycles was 6 (range 1-18). Treatment was discontinued for toxicity in 15.8% of the cases. Partial response was seen in 43.2% of pts, stable disease in 32.6% and disease progression as best response in 18.9% of cases. Overall TTP was 13.7 months and was independent of prior systemic treatment (1st line vs. >1st line, 13.6 vs. 25.3 months, P= 0.54). Functionality had no impact on median TTP. There was no difference between pts with G1 and G2 NET (TTP 21.3 vs. 16.4 months, P=0.78). Median OS was 27.6 months (range 0.8-174 months). In pts with at least two extrapancreatic disease sites (34.7%) median OS was inferior compared to pts with one disease site involvement (37.3 vs. 70.5 months, P=0.02). Conclusions: The combination of STZ and 5FU was associated with a considerable objective response rate in advanced G1/G2 pNETs who had prior disease progression. Efficacy of treatment was not depending on therapy line or grading (G1 vs. G2). Objective response rate is higher than those observed with targeted drugs. This finding along with good tolerability of the treatment strengthens the durable value of this chemotherapy in the era of targeted drugs for the outcome of pts with pNETs.