Neuroendocrine Tumors and Chemo

The Neuroendocrine System

The endocrine system is a complex interplay of glands that produce hormones or chemicals but exert their action in a distant site or target. For example, the pancreas, through its islets of Langerhans cells, produces insulin which exerts its action on the different cells in the body to absorb digested glucose from the blood. Hormones are chemical messengers that have a regulatory function, often being controlled by the impulses from the hypothalamus (part of the brain) in a negative feedback system. Thus the term neuroendocrine is given to emphasize the interplay between the nervous and the endocrine systems. They have an important role in maintaining balance or homeostasis in the body.

The neuroendocrine system is composed of the pituitary gland, the pineal gland, the hypothalamus, the thyroid gland, the parathyroid glands, the thymus, the adrenal glands, the ovaries (in females) or testes (in males), and the pancreas. There are also neuroendocrine cells found in the organs of the digestive tract mainly the stomach, the small and large intestines, and the pancreas.

Neuroendocrine Tumors

NETs are new growths that can be found in any of the organs mentioned above, but most commonly in the digestive tract. Occasionally these tumors are also found as liver metastases without a clear primary organ of origin.

NETs are rare, since they are found in less than 2 percent of malignancies found in the digestive tract. The most common type of these is the carcinoid tumor, which grow slowly compared to the two other types, the pancreatic endocrine tumor and the gastropancreatic NET.

Signs and symptoms of NET may vary depending on the organ involved. However, most of these tumors are not symptomatic till late in the course of the disease, and signs and symptoms may be vague and non-specific, such as weight loss, loss of appetite, diarrhea, unusual bleeding or discharge, abdominal discomfort, night sweats, etc.

Diagnosis is likewise difficult because of the late manifestations. Detection usually follows when the cancer cells have spread to other organs (metastasis) and symptoms have occurred. Laboratory studies used to arrive at a diagnosis are usually multiple, including blood tests, x-ray, CT scan, MRI and biopsy.

Staging of the disease depends on tumor size, extent of spread and involvement of lymph nodes.

Neuroendocrine Tumors and Chemo

Small and localized tumors may respond to surgery. However, tumors are usually extensive or widespread, and surgery is often not effective in treating the malignancy.

Radiotherapy, using high-energy particles like x-rays to target and kill cancer cells, or implants, as in internal radiation therapy or brachytherapy may be a choice when surgery cannot eliminate the tumors.

Other options include endocrine or hormone suppression and targeted therapy, which targets specific genes and proteins that contribute to cancer growth.

Chemotherapy (chemo) is a mode of treatment where drugs are given systemically to kill cancer cells. These cytotoxic drugs may be used singly or in combination either orally or intravenously. Although these tumors may be resistant to chemo, recent studies have raised new hope for the effectiveness of some drugs in stabilizing the disease.

Chemotherapy for Neuroendocrine Tumors

Previous studies of single agent chemotherapy have yielded different results using:

• Streptozocin
• 5-fluorouracil (5-FU)
• Cisplatin
• Doxorubicin
• Dacarbazine
• Paclitaxel
• Gemcitabine
• Epirubicin
• Temozolomide
• Thalidomide

Of these drugs, streptozocin, doxorubicin, 5-FU and dacarbazine were most active when used singly or in monotherapy. Factors that influenced response to therapy are the age of the patient, the general health condition, tumor size and extent of spread.

Polytherapy or the combination of chemotherapeutic drugs has been found to produce more positive results in terms of radiologic and biochemical response. For instance combining streptozocin with doxorubicin showed better results than when either was used alone. Other combinations of two or three drugs have also been studied.

In a study done in several medical centers in London (published recently in the British Journal of Cancer), a combination of 5-FU, cisplatin, and streptozocin given for up to six cycles administered every three weeks was found to improve response to therapy in 33 percent of patients enrolled. The combination of these drugs also proved to be tolerable in many of them.

Another recent study suggests the use of a biological marker Ki-67 which can predict response to chemotherapy. It is postulated that this measurement is helpful in deciding whether chemo should be a first option in the algorhythm of treatment modalities.

Chemotherapy for neuroendocrine tumors may be done alone or in combination with other treatment options. The decision to use one or more of these modalities depend on the type of tumor, stage of the disease, age and the general health of the patient.

References

Endocrine-Related Journals, “Chemotherapy and role of the proliferation marker Ki-67 in digestive neuroendocrine tumors” accessed 12/02/10

https://erc.endocrinology-journals.org/cgi/reprint/14/2/221

Cancer Consultants, “Combination Chemotherapy Effective and Tolerable for Neuroendocrine Tumors” accessed 12/02/10

https://professional.cancerconsultants.com/oncology_main_news.aspx?id=44805

Cancer.net, “Neuroendocrine Tumor” accessed 12/02/10

https://www.cancer.net/patient/Cancer+Types/Neuroendocrine+Tumor?sectionTitle=Overview