New advances in the treatment of neuroendocrine lung tumors

This review examines the advances in treatment options for neuroendocrine (carcinoid) tumors of the lung.

Neuroendocrine cells are found on the linings of organs such as the lungs, stomach or intestines. Normally, these cells have nerve-like and endocrine-like (hormone-making) properties, which help in regulating the function of these organs. In the lungs, neuroendocrine cells make adrenaline and similar substances, which help control air and blood flow. However, like most cells in the body, neuroendocrine cells can go through changes that make them grow too much and become cancerous, leading to neuroendocrine tumors. Types of neuroendocrine tumors in the lungs include typical carcinoid tumors (TC), atypical carcinoid tumors (AC), large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC). Although they are often considered as one condition, each type of neuroendocrine cancer has distinct characteristics. For instance, LCNEC is much more likely to be caused by cigarette smoking than the other, AC is more likely to spread to the lymph nodes and other areas of the body compared to TC, while SCLC is one of the fastest growing and spreading cancers, and is studied separately from other neuroendocrine tumors. Despite these differences, they are generally treated as one disease. Since treatment options for these three types of lung cancer have not been well-researched, the optimal treatment regimens for each are not yet known and they depend on tumor type and extension of the disease.

Currently, the main treatment for confined TC, AC and LCNEC is surgery to remove either the tumor alone and preserve as much lung tissue as possible (resection), or an entire portion of the affected lung (lobectomy). The 5- and 10-year survival rates following surgery are more than 90% for TC, and 70% and 50%, respectively, for AC, with better 20-year survival rates following a lobectomy. Lobectomy is the preferred treatment for LCNEC, since it is more aggressive and has a great risk of reoccurring in the same lung. Very few clinical trials have examined adjuvant (additional to surgery) treatments such as chemotherapy and radiotherapy for TC, AC and LCNEC. Small studies have shown that chemotherapy drugs such as irinotecan or etoposide (usually given for SCLC) can improve the 5-year survival to 88.9% after at least 2 cycles in LCNEC. In more advanced neuroendocrine tumors, combinations of chemotherapy drugs, such as 5-fluorouracil and doxorubicin or streptozotocin, have been shown to lead to an overall response rate (tumor shrinkage) of 16% in both TC and AC, and a 5-year survival rate of 93% for TC and 73% for AC.

Since neuroendocrine tumors often secrete serotonin or other similar hormones, they cause carcinoid symptoms (diarrhea, face reddening, heavy breathing, or rapid heart rate). Therefore, a drug that blocks the action of these hormones called a somatostatine analogue (behaves like somatostatine, a naturally occurring hormone), such as octreotide, has been shown to effectively control carcinoid symptoms and also to have anti-tumor properties. Newer therapies include radiolabelled somatostatine analogues (a drug that targets hormone-secreting cancer cells and kills them with radiation) such as 90Y-DOTATOC and 77Lu-DOTATATE. Drugs that target specific proteins in tumor cells (everolimus) to block their growth have also been shown to slow the progression of the disease.

There are a number of promising treatment regimens for TC, AC, and LCNEC, but more clinical trials need to determine their actual efficacy and safety. Moreover, TC, AC, and LCNEC need to be examined as separate conditions, as each have their own characteristics and respond differently to treatments.

Discuss with your physician about which types of treatment are the most appropriate in your situation.