Sunitinib for the treatment of metastatic paraganglioma and vasoactive intestinal polypeptide-producing tumor (VIPoma).

OBJECTIVES: Gastroenteropancreatic neuroendocrine tumors (NETs) are rare tumors of the endocrine and nervous systems. Whereas early surgical resection can significantly reduce tumor mass, there are few data available concerning the control of hormonal secretion and associated symptoms. Studies have shown that the tyrosine kinase inhibitor sunitinib significantly prolongs progression-free survival in patients with pancreatic NETs. Here, we present 2 case reports of sunitinib in patients with different types of NETs. METHODS: The patients were a 12-year-old boy with metastatic vasoactive intestinal polypeptide-producing tumor (VIPoma) and a 70-year-old woman with metastatic paraganglioma/NET. Both were treated in an outpatient clinical setting. Sunitinib was titrated to 37.5 mg on a continuous daily dosing schedule in the patient with VIPoma, and the dose was 50 mg/d (4 weeks on, 2 weeks off) in the patient with the paraganglioma/NET. RESULTS: The patient with the paraganglioma/NET had a confirmed complete radiographic response and the patient with VIPoma had a confirmed partial response (Response Evaluation Criteria in Solid Tumors). In both patients, improvements were observed in biochemical tumor markers, clinical responses, and quality of life. CONCLUSIONS: In these patients, sunitinib reduced biochemical markers and stabilized or reduced tumor bulk and may therefore be a potential therapeutic option for these tumor types.

[VIPoma: surgical treatment]. / VIPoma: trattamento chirurgico.

This paper reports a case of pancreatic VIPoma with widespread hepatic metastasis which was treated for approximately 2 years with a synthetic somatostatin analog (SMS 201/995). The treatment of choice in cases in which the tumour was fully removable is surgical resection. This occurred rarely since approximately 80% of VIPomas are malignant and are operated late when local infiltration is already widespread; in addition, 50% of cases are already metastasised at diagnosis. In this case, due to the infiltration of the superior mesenteric artery by the primary tumour it was necessary to carry out a left pancreasectomy which included two-thirds of the neoplastic mass. This was justified by slow tumour growth and also facilitated control of diarrhea and ensured a greater efficacy of possible postoperative chemotherapy. The use of synthetic somatostatin analog (SMS 201/995) enabled diarrhea to be satisfactorily controlled and is therefore specifically indicated for this type of tumour. NSE serum assay (neuron specific enolase) allowed the evolution of disease to be monitored during follow-up.

Characterization of an alpha-amidating activity in a human pancreatic tumour secreting vasoactive intestinal peptide (VIP).

A case of watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome due to a pancreatic tumour and identified by VIP plasma level, VIP immunocytochemistry, and ultrastructural analysis of tumour sections, is reported. Since VIP is the mediator of the syndrome and is biologically active under its amidated form, the enzymatic alpha-amidating activity was investigated and characterized in tumour extract; using the synthetic substrate D-Tyr-Val-Gly, the enzyme displayed an optimal activity at pH 7.0, under aerobic conditions and with 35 microM CuSO4 and 3 mM ascorbate as co-factors. The Kmax and Vmax values of the enzymatic activity were 133.7 microM and 26.9 pmol/h/micrograms protein respectively. Its molecular weight, determined by molecular sieving, was close to 36 kDa. Other tumours of the human endocrine pancreas were also investigated for the enzymatic activity. The clinical interest of studying the regulation of the alpha-amidating activity in such tumours is discussed.