Glucagonoma Treatment & Management

Updated: Dec 16, 2022
  • Author: Ricardo R Correa Marquez, MD, EsD, FACP, FACE, FAPCR, CMQ, ABDA, FACHT; Chief Editor: George T Griffing, MD  more...
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Treatment

Approach Considerations

Treatment of glucagonoma may vary by stage of disease. If possible, surgical resection and debulking procedures are performed, as resection is the only curative therapy. [23, 24, 25] Control of symptoms is possible at the early stages of disease with somatostatin analogs (SSA). Peptide receptor radionuclide therapy (PRRT) with lutetium Lu 177-dota-tate (177Lu-DOTATATE; Luthera) has been proposed as a first-line therapy in patients with glucagonoma and secreting metastasis. However, since the number of glucagonoma cases is so small, it has not yet been possible to draw results on the actual benefit of this therapy, especially in terms of long-time survival. [26]

Patients with glucagonoma who have severe weight loss may require a period of total parenteral nutrition as part of the preoperative preparation. Antibiotics, corticosteroids, amino acids, and zinc supplementation may improve severe skin rash. Octreotide is also useful to help improve the perioperative condition of these patients. Prophylaxis for venous thrombosis, including and the subcutaneous administration of low-dose heparin are mandatory for all patients during the perioperative period.

In patients for whom surgery is not feasible, consider administering streptozotocin and doxorubicin or streptozotocin and 5-fluorouracil.

In patients with widespread metastases, consider hepatic artery catheterization for infusion of doxorubicin, cisplatin, and mitomycin-C. Such treatment can often produce colliquative necrosis and mass reduction. In addition, administering octreotide before, during, and after locoregional therapy may stop the crisis caused by the massive release of glucagon.

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Medical Care

Some drugs can cause partial regression of a neoplastic mass or improvements in the symptoms of necrolytic migratory erythema (NME). [23]  In the literature, good results have been obtained with streptozotocin plus either doxorubicin or 5-fluorouracil, via selective damage of islet cells. [21]

Long-acting octreotide, analogous to human somatostatin, causes NME symptom regression in some, but not all, patients. [20, 21, 27, 28]

Everolimus is approved by the US Food and Drug Administration (FDA) for progressive neuroendocrine tumors located in the pancreas (PNET) that are metastatic or are not surgically resectable. Approval was based on a study that showed an increased median progression-free survival (PFS) of 11.0 months with everolimus compared with 4.6 months with placebo. [29]

Sunitinib is also approved by the FDA for PNET, on the basis of a study that was discontinued after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group but an improvement in PFS in the sunitinib group. Median PFS was 11.4 months in the sunitinib group, versus 5.5 months in the placebo group. [30]

Lanreotide (Somatuline Depot) is approved by the FDA as a once-monthly deep subcutaneous injection for unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), to improve PFS. Approval was based on the multicenter, international CLARINET trial (n=204), which demonstrated a significantly prolonged PFS in those who received lanreotide (hazard ratio, 0.47; 95% confidence interval [CI], 0.30 - 0.73; P < 0.001; log-rank test). [31]

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Surgical Care

Resection

In some patients, removal of the tumor may reverse symptoms. Several authors have reported the clinical palliation of symptoms from surgical debulking of the tumor. [32]

Beyond neoplasm removal, healthy surrounding parenchyma and locoregional lymph nodes can be resected because they may be metastatic or, more rarely, the primary site of the tumor.

Laparoscopic resection has proved a safe and feasible option for treatment of pancreatic endocrine tumors in selected patients, although most published studies have been retrospective and with small patient numbers, due to the rarity of the disease. [33, 34, 35] Laparoscopic resection is used for tumors that are benign or that pose low risk of malignancy. [35]

Leakage of pancreatic juices from postoperative pancreatic fistulas (POPFs) is a common complication of pancreatic resection. Preoperative use of the somatostatin analogue pasireotide has been studied but its efficacy in reducing clinical relevant POPFs remains questionable, and its expense and adverse effects limit its usefulness. [36, 37] Placement of a drain at the time of surgery may be considered, although studies of this practice have yielded disparate results, and in any case have included only a minority of patients with neuroendocrine tumors. [38]

Given the risk of recurrence, even patients with completely resected glucagonomas require close follow-up, especially in the first 3 years after resection. Guidelines suggest maintaining follow-up for at least 10 years in most cases. [39]

Embolization

Patients with liver metastases and severe symptoms caused by tumor bulk or hormone-release syndromes may benefit from procedures that reduce hepatic arterial blood flow to metastases. The videos below demonstrate bland embolization of the right hepatic artery in a patient with metastatic neuroendocrine tumors.

Bland embolization of the right hepatic artery in a patient with metastatic neuroendocrine tumors: Part 1. Courtesy of Memorial Sloan-Kettering Cancer Center.
Bland embolization of the right hepatic artery in a patient with metastatic neuroendocrine tumors: Part 2. Courtesy of Memorial Sloan-Kettering Cancer Center.
Postprocedure computed tompgraphy scans after bland embolization of the right hepatic artery in a patient with metastatic neuroendocrine tumors. Courtesy of Memorial Sloan-Kettering Cancer Center.

Hepatic arterial occlusion with embolization or chemoembolization should cause necrosis of the metastases without damaging the healthy hepatic parenchyma, which is supplied from the portal circulation. [40, 41] This treatment may also be combined with systemic chemotherapy in selected patients.

Transplantation

Multimodal therapeutic interventions including liver transplantation have been reported, but further studies are needed to validate such time-consuming and expensive procedures. [42]

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Consultations

Because glucagonomas may cause mucocutaneous lesions, endocrine disturbances, and optic and psychic disturbances, consultations may be very helpful for differential diagnosis and therapy. Consultants may include dermatologists, neurologists, endocrinologists, and ophthalmologists.

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Diet

In patients with glucagonoma, providing a supplemental protein supply in order to furnish amino acids is useful. In more severe cases, such supplementation can be administered intravenously. Ingestion of essential fatty acids (eg, olive oil), zinc, vitamins, and minerals is also helpful.

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