Low dose DTIC is effective and safe in pretreated patients with well differentiated neuroendocrine tumors

Streptozocin (STZ) based chemotherapy is recommended for patients with metastatic pancreatic neuroendocrine tumors (pNET). Temozolomide as mono- or combination therapy has been suggested to be a promising alternative. However, the treatment is costly and not approved for the treatment of pNETs. Dacarbazine (DTIC) shares the active metabolite with temozolomide and is broadly available at a low cost. The aim of this study was a retrospective evaluation of the efficacy and tolerability of a lower dose DTIC-regimen in patients with progressive advanced NETs.

We retrospectively analyzed 75 patients with NETs predominantly of pancreatic origin treated at our center between 1998 and 2013. 650 mg/m(2) of DTIC were administered intravenously over 60 min every 4 weeks. Morphological response was assessed according to RECIST1.1 criteria. The median progression free survival (PFS) was calculated using Kaplan-Meier and Cox regression methods, respectively. Univariate analyses of possible prognostic markers were performed.

The objective response rate (ORR) was 27 % for the entire cohort and 32 % in 50 pNET patients, respectively. Stable disease (SD) was documented in 29 patients (39 %). Median PFS (mPFS) in patients receiving DTIC was 7 months (3.9-10; 95 % confidence interval). Radiological and biochemical response were the only significant prognostic markers for longer PFS in univariate analysis. Treatment was well tolerated. Nausea was the most common side effect (31 %), only one case (1.3 %) of grade 3 toxicity (vomiting) occurred.

Low dose DTIC chemotherapy is an effective and well-tolerated treatment option in patients with progressive well differentiated neuroendocrine neoplasms, especially of pancreatic origin.