Neoplasms of the Endocrine Pancreas Medication

Updated: Feb 01, 2018
  • Author: Evan S Ong, MD, MS; Chief Editor: Neetu Radhakrishnan, MD  more...
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Medication

Medication Summary

The goals of palliative medical therapy for pancreatic endocrine neoplasms are (1) the reduction of symptoms related to hormonal excess and (2) the control of tumor cell proliferation.

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Antisecretory agents

Class Summary

Used to modulate the release of gastroenteropancreatic hormones from both normal and neoplastic APUD cells in the treatment of pancreatic endocrine tumor syndromes to reduce specific symptoms related to hormonal excess.

Octreotide (Sandostatin)

Somatostatin analogue that binds somatostatin receptors on pancreatic endocrine tumor cells and inhibits release of many gastroenteropancreatic hormones.

Useful adjunct in palliative treatment of patients with most functional metastatic pancreatic endocrine tumors. Evidence suggests that it may also have antiproliferative effects in rare cases. However, symptomatic and antiproliferative effects last only months and are probably of short duration secondary to down-regulation of cell-surface somatostatin receptors (Maton, 1989). Because octreotide is a somatostatin agonist, it is not useful in the treatment of patients with somatostatinoma syndrome (Pless, 1986). Doses of 300-600 mcg/d or higher seldom result in additional biochemical benefit.

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Radiopharmaceuticals

Class Summary

Radiolabeled somatostatin analog binds to somatostatin receptor-expressing cells.

Lutetium Lu 177-dota-tate (Lutathera)

Binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSRT2). Upon binding to somatostatin receptor-expressing cells, including malignant somatostatin receptor-positive tumors, the compound is internalized. Beta emission from Lu 177 induces cellular damage by forming free radicals in somatostatin receptor-positive cells and in neighboring cells. It is indicated for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.

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Immunotherapeutics

Class Summary

Used to modulate host immune responses to neoplastic cells. Control of tumor cell proliferation is the goal when these agents are used to treat patients with pancreatic endocrine tumor syndromes.

Interferon alfa-2a (Roferon-A) and alfa-2b (Intron A)

Protein product manufactured by using recombinant DNA technology.

Pancreatic endocrine tumor patients treated with human leukocyte interferon have objective response rates of 77%, with effects lasting > 1 year in some cases.

Responses represent primarily decreased hormone production rather than objective reduction in tumor bulk (Oberg, 1989). Mechanisms of hormone reduction and antitumor activity are not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response likely have important roles.

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Chemotherapeutics

Class Summary

Primarily reserved for patients with pancreatic endocrine neoplasms that are metastatic and/or unresectable.

While most experts agree that chemotherapy is indicated in patients who have symptoms from tumor bulk or uncontrolled syndromes of hormone excess that cannot be palliated with other means (eg, cytoreductive surgery, cryosurgery, radiofrequency ablation, hepatic artery embolization), no consensus exists on when therapy should be started in asymptomatic patients with metastatic or recurrent disease. One common practice is to reassess patients at 3- to 6-month intervals after diagnosis of metastatic or recurrent disease. Patients with clear tumoral progression are treated with chemotherapy, whereas those with stable lesions are monitored. No benefit from chemotherapy has been demonstrated in patients with metastases to only lymph nodes.

Studies of patients with advanced islet cell carcinomas in which streptozocin alone was compared with streptozocin plus 5-fluorouracil (5-FU) have overall response rates as high as 63%, and survival rates increased by as much as 1 year with combination therapy, although single-agent therapies have generally yielded lower response rates. [108] A study of streptozocin plus doxorubicin compared with streptozocin plus 5-FU revealed a better response rate of 69% and an increased survival rate for patients treated with streptozocin plus doxorubicin. [109] Use of liposomal doxorubicin markedly reduces the risk of cardiac toxicity with this regimen, while efficacy remains comparable. [110] In a study of patients with all types of GI neuroendocrine tumors, streptozocin was found to be more effective in patients with islet cell tumors than in those with carcinoid tumors. [95] However, a small study of patients with islet cell carcinomas treated with the combination of streptozocin, doxorubicin,and 5-FU had a response rate of only 54% and no complete responses. [111]

A number of other chemotherapeutic drugs, such as the taxanes, platinum compounds, gemcitabine, camptothecin analogues, targeted receptor antagonists, and antiangiogenesis/antiendothelial agents, have demonstrated activity against pancreatic endocrine tumors, but none has been adequately evaluated in these neoplasms or has demonstrated results as good as those of various combinations of streptozocin, doxorubicin, and 5-FU. [82]

Streptozocin (Zanosar)

Has diabetogenic action in some animals that is correlated with selective uptake of the drug by pancreatic beta cells (Schein, 1973). As a result, streptozocin is uniquely helpful in the treatment of insulinoma. Also inhibits cell proliferation and is cytolytic. Interferes with normal DNA function by means of alkylation and protein modification.

Doxorubicin (Adriamycin, Rubex)

Inhibits topoisomerase II and produces free radicals that may destroy DNA. Combination of these events can inhibit growth of neoplastic cells.

Fluorouracil (Adrucil)

Fluorinated pyrimidine antimetabolite that inhibits thymidylate synthase and interferes with RNA synthesis and function. Has some effect on DNA.

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