Endocrine Abstracts

Introduction: VIPomas are rare neuroendocrine tumors (NET), usually located in the pancreas that secrete vasoactive intestinal polypeptide (VIP) leading to high-volume watery diarrhea and complications such as hypokalemia, acidosis and dehydration. The management of VIPoma symptoms is often challenging when surgical resection of all the lesions is not feasible. Treatments are then based on somatostatin analogs (SSA) and may also include hepatic chemoembolization, systemic chemotherapy, targeted therapies, with reported efficacy of sunitinib on hormonal secretion or Peptide Receptor Radionuclide Therapy (PPRT). The combination of these treatments on anti-secretory effects is unknown.

Clinical case: A 61 years-old woman had a non-functioning metastatic grade 2 (Ki67=15%) well differentiated pancreatic NET, misdiagnosed during the first 2 years of management as hepatocellular carcinoma (HCC). Therefore, she received Sorafenib and Lenvatinib according to HCC guidelines. After expert pathological review and final diagnosis of NET, she was started on SSA. Six months after SSA initiation, metachronous VIP secretion appeared, contemporary with diffuse liver progression and VIPoma symptoms: severe watery diarrhea leading to continuous hospitalization during four months. Symptoms management required high doses of I.V. SSA (octreotide 2400 μg/day). The patient was not eligible for locoregional treatment due to diffuse hepatic miliary invasion. Sunitinib lead to rapidly controlled symptoms but required dose adjustments due to hematological toxicity, and disease progression occurred after 2 months. Chemotherapy with 5FU-Oxaliplatin and the anti VEGF agent Bevacizumab was ineffective. At that time, the 68Ga-DOTATOC PET showed avidity for all lesions. Due to the previously symptomatic response to Sunitinib, Lenvatinib was initiated at reduce dosage (10 mg/day) for hormonal secretion control, together with 2 cycles of 177-Lu-Dotatate (7,4 GBq). This combination resolved rapidly, completely and sustainably VIPoma symptoms, associated with a massive decreased of plasma VIP level after one month (from 20 to 3 times over the upper limit normal) and a morphologic partial response after three months. Lenvatinib led to constipation and, whenever, the patient stopped taking the drug, the diarrhea recurred. Therefore, maintenance Lenvatinib alone is ongoing with no functional symptoms since four months.

Conclusion: Urgent management of severe uncontrolled VIP secretion can lead to unusual treatment combinations in order to control both hormonal secretion and tumor growth. The anti VEGF activity may not be the only mechanism of VIP secretion inhibition of Sunitinib owing to the lack of efficacy of Bevacizumab in our case. The long-term toxicity of the combination reported here is unknown and remains to be studied.