Lay Summary: Chemotherapy is not very useful for neuroendocrine cancers. A new promising drug, avastin, is being studied.
Neuroendocrine cancers come in different varieties that range from carcinoid to small cell. Carcinoid tumors are rare, slow-growing tumors that originate in the cells of the neuroendocrine system. Treatment decisions for patients with carcinoid tumors are complex and related to the location of the primary tumor and whether or not metastasis has occurred. The role of chemotherapy for NETs is uncertain but is being actively researched. It is essential to consider the tumour types individually in view of their varying response to chemotherapy and the indications to use it. Certain prognostic factors may also help in determining the use of chemotherapy and one paper showed an inverse correlation between imaging with SSRS radioscintigraphy and response to treatment. Response to chemotherapy in patients with strongly positive carcinoid tumours was of the order of only 10% whereas patients with SSRS negative tumours had a response rate in excess of 70%. The highest response rates with chemotherapy are seen in the poorly differentiated and anaplastic NETs: response rates of 70% or more have been seen with cisplatin and etoposide based combinations. These responses may be relatively short lasting in the order of only 8–10 months.Response rates for pancreatic islet cell tumours vary between 40% and 70% and usually involve combinations of streptozotocin (or lomustine), dacarbazine, 5-fluorouracil, and adriamycin. However, the best results have been seen from the Mayo clinic where up to 70% response rates with remissions lasting several years have been seen by combining chemoembolisation of the hepatic artery with chemotherapy. The use of chemotherapy for midgut carcinoids has a much lower response rate, with 15–30% of patients deriving benefit, which may only last 6–8 months. Again, the most commonly used agents will be those listed above. The management of pulmonary carcinoids is more likely to involve a platinum and etoposide combination and may reflect the fact that a pulmonary oncologist will be involved and that bronchial carcinoids may represent one end of the spectrum, which includes small cell lung cancer, which is exquisitely chemosensitive. If possible, patients should be entered into formal trials of new agents. Avastin is a promising new agent which is only now beginning to be studied in carcinoid.Avastin, or Bevacizumab is a monoclonal antibody that may inhibit cancer growth by blocking blood flow to tumors. Adding bevacizumab to combination chemotherapy may be a better way to block tumor growth than giving either type of therapy alone. The FOLFOX plus bevacizumab combination is being studied in patients with neuroendocrine tumors because FOLFOX appears to inhibit the growth of a variety of different tumor types but has not yet been tested in this disease. In addition, neuroendocrine tumors appear to depend on blood vessels for growth suggesting that they may respond to a treatment like bevacizumab. One such trial can be viewed at http://www.carcinoid.org/medpro/docs/USFnetClinTrial2005.pdf.
Chemotherapy response rates are low and some of the agents studied include 5-fluorouracil, BiCNU® (carmustine), CeeNU® (lomustine), doxorubicin, dacarbazine and Zanosar. Temodar is an oral analogue of dacarbazine. Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses. Etoposide and cisplatin have been used for over a decade based on several phase II studies showing response rates of around 70% in poorly differentated NET.
NCCN on CARC-5 lists chemotherapy as an option(category 3) but does not list etoposide and carboplatin.
Researchers from the Dana-Farber Cancer Center have reported that the oral administration of Temodar (temozolomide) and Thalomid (thalidomide) in patients with metastatic neuorendocrine tumors results in a 40% biochemical response rate and a 25% radiologic response rate. The details of this report appeared in the January 20, 2006, issue of the Journal of Clinical Oncology.
There are a number of reports of phase II studies of this regimen and it should be considered "supported" by medical literature.
Afinitor is reviewed separately. Capecitabine ( Krzyzanowska et al. 2006), gemcitabine ( Kulke et al. 2004a) and topotecan ( Ansell et al. 2004) have all been shown to be inactive as monotherapy in these tumours.
Kulke MH, Stuart K, Enzinger PC, et al. Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. Journal of Clinical Oncology . 2006;24:401-406.
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