Treatment of Neuroendocrine Cancer

Summary

Treatment options for neuroendocrine tumours (NETs) depends not only on the type and location of the tumour, but also whether there are signs and symptoms. In fact, various treatment options for the treatment of NETs include surgery, chemotherapy, immunotherapy, targeted drug therapy, PRRT, and radiation therapy.

Introduction

Treatment options for neuroendocrine tumours depend not only on the type and location of the tumour, but also whether there are signs and symptoms of excess hormones produced by the tumour.

In general, treatment options for neuroendocrine tumours may include:

Surgery:

• Doctors perform the surgery on patients in order to remove the tumour. If needed, the surgeon tries to remove the entire tumour and also some healthy tissue around it. If the doctor cannot remove the tumour completely, it may be helpful to remove it as much as possible.

Chemotherapy:

• Chemotherapy uses powerful drugs to destroy tumour cells and one can explicitly administer it through a vein in hand or used as a tablet. Doctors, in fact, often recommend chemotherapy after surgery if there is a risk of a recurrence of the neuroendocrine tumour. A doctor can also use it for the tumors he/she cannot remove surgically. In other words, advanced tumours. In fact, well-differentiated G1 and G2 NETs can be used alone or in combination with antimetabolites (5-fluorouracil, capecitabine) in several chemotherapy protocols consisting primarily of alkylating agents (streptozotosine, dacarbazine and temozolomide). However, there are no major phase 3 clinical trials that provide convincing, evidence-based recommendations for using the best diet in the right order^​1​.

Targeted drug therapy:

• Targeted drug therapy, indeed focuses on specific abnormalities in tumour cells. However, by blocking these abnormalities, targeted drug therapy can lead to the death of tumour cells. In fact, a doctor gives targeted drug therapy in conjunction with chemotherapy for advanced NETs.

Excessive activation of mTOR has been observed in several cancer models, including NET, and inhibition of mTOR by rapamycin and analogs such as RAD001 known as everolimus (Afinitor, Novartis Oncology) have been shown to inhibit tumour cell proliferation. It, in fact, slows the growth of tumours. 

Sunitinib maleate (Sutent®, Pfizer, Inc.) is a tyrosine kinase inhibitor (TKI) capable of irreversibly inhibiting several kinases, including the VEGFR family, against several solid tumours (e.g., renal cell carcinoma and gastrointestinal cancer). It is an anticancer and antiangiogenic agent which effect stromal tumours). Sunitinib is, in fact, effective against PNETs in both preclinical and clinical studies^​2​.

Peptide receptor radionuclide therapy (PRRT): 

• PRRT is a combination of a drug that targets cancer cells and a small amount of radioactive material. This allows the direct delivery of radiation to the cancer cells. PRRT, Lutetium Lu 177 dotate (Luthera) is used to treat advanced neuroendocrine tumours.

Peptide receptor radionuclide therapy (PRRT) with a 90-yttrium-labelled compound, or 177-Lu-DOTATATE, has been used in uncontrolled studies of various NET patients overtime the past 15 years. Various studies have shown that it stabilizes the disease in most patients and cures tumours in 15-35% of patients^​3​.

Immunotherapy:

• Immunotherapy is indeed a rapidly growing therapeutic area for the treatment of various types of cancer. The immune checkpoint pathway acts by physiologically activated T cells in order to suppress autoimmune activity. Programmed death receptor 1 (PD-1) is an inhibitory receptor on T cells that interacts with the ligands PD-L1 and PD-L2 to reduce the anticancer response of T cells. The first study showed that antibodies to PD-1 or PD-L1 could enhance the anticancer activity of T cells with acceptable protection and tolerability. Pembrolizumab is a selective and potent humanized monoclonal antibody with a high affinity for the PD-1 receptor^​4​. Although it has been reported to be effective in other solid tumours (lung carcinoma, RCC, melanoma, and Merkle cell carcinoma), experience with NET patients is very limited, mainly showing stable disease as the best response^​5​.

Medications to control excess hormones:

• The doctor may prescribe medications in order to control the signs and symptoms if the neuroendocrine tumour releases additional hormones.

Radiation Therapy:

• Radiation therapy uses strong energy rays such as X-rays and protons to destroy tumour cells. Some types of neuroendocrine tumours may respond to radiation therapy. When surgery cannot be performed, it may be recommended. Selective Interval Radiation Therapy (SIRT) – Radiation embolization using resin-based (surfer) and glass-based (thermosphere) micron-sized particles loaded with Yttrium-90 radioactive isotopes that attach directly to the network are increasingly being used^​6​.

References