DOTA-TOC in Metastasized Neuroendocrine Tumors

The investigators aim to explore the efficacy of [90Y-DOTA]-TOC and [177LuDOTA]-TOC therapy in advanced neuroendocrine cancer. Therefore, the investigators assess response, survival and long-term safety profile of systemic [90Y-DOTA]-TOC and [177LuDOTA]-TOC treatment in metastasized neuroendocrine cancer patients. Adverse events are assessed according to the criteria of the National Cancer Institute. Survival analyses are performed using multiple regression models.

Background: Systemic treatment with the 90Yttrium (90Y) labeled, tetraazacyclododecanetetraacetic acid (DOTA) modified somatostatin analog Tyr3-octreotide (TOC) was introduced in 1998 (Otte et al. Lancet 1998). [90Y-DOTA]-TOC is administered intravenously and binds to the somatostatin receptor subtype 2, located on the surface of the tumor cell, and exerts its cytotoxic effects by β-irradiation. The treatment has moderate acute hematologic and nephrologic toxicity and has developed into a promising therapeutic tool for tumors expressing its target receptor (Iten et al. Clin Cancer Res 2007, Iten et al. Cancer 2009). Study Aim: To explore the efficacy of [90Y-DOTA]-TOC and [177LuDOTA]-TOC therapy in advanced neuroendocrine cancer. Study Hypothesis: Response to DOTA-TOC is correlated with prolonged survival. Study Type: Clinical phase II, single-center, open-label trial Patients: 1500 patients

Intravenous injections of DOTA-TOC. Repeated treatment cycles for responders, except in case of renal toxicity loss of patient transferability or denial of further treatment.

Inclusion Criteria: histologically confirmed neuroendocrine cancer stage IVc disease by definition of the American Joint Committee on Cancer, i.e. occurrence of distant metastases visible tumor uptake in the pretherapeutic somatostatin receptor subtype 2 scintigraphy (111In-Octreoscan) Exclusion Criteria: concurrent anti-tumor treatment secondary malignancies pregnancy breast-feeding incontinence severe concomitant illness including severe psychiatric disorders

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Iten F, Muller B, Schindler C, Rasch H, Rochlitz C, Oertli D, Maecke HR, Muller-Brand J, Walter MA. [(90)Yttrium-DOTA]-TOC response is associated with survival benefit in iodine-refractory thyroid cancer: long-term results of a phase 2 clinical trial. Cancer. 2009 May 15;115(10):2052-62. doi: 10.1002/cncr.24272.

Marincek N, Jorg AC, Brunner P, Schindler C, Koller MT, Rochlitz C, Muller-Brand J, Maecke HR, Briel M, Walter MA. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study. J Transl Med. 2013 Jan 15;11:17. doi: 10.1186/1479-5876-11-17.