Neuroendocrine tumors responded to new chemotherapy combination in trial

15/1/2014

Promising interim results of a new chemotherapy combination against with advanced neuroendocrine tumors show promise during a trial, for 95% of patient group. The group contained patients whose disease worsened after standard high-dose octreotide.

The chemotherapy combination is called “CAPTEM” and includes a combination of capecitabine and temozolomide.

The responses were long-lasting, with a median progression-free survival of 30 months, and most patients experienced only mild side effects. The authors believe that CAPTEM may eventually replace all other second-line therapies for advanced neuroendocrine tumors because its efficacy is far superior.

“In this study we’re seeing patients who had been given six months to live that are still alive eight years after starting CAPTEM. The regimen was effective even in patients with tumors that hadn’t responded to any other standard treatment, including chemotherapy, high-dose octreotide, small molecule inhibitors, radiation or surgery,” said lead study author Robert Fine, MD, an associate professor of medicine at New York Presbyterian Hospital-Columbia University Medical Center in New York, N.Y. “The rate of serious side effects was low with CAPTEM. We had no hospitalizations or treatment-related deaths.”

Neuroendocrine tumors begin in the hormone-producing cells of the body’s neuroendocrine system. Neuroendocrine cells are found throughout the body and perform specific functions, such as regulating air and blood flow through the lungs and controlling the speed at which food moves through the gastrointestinal tract. An estimated 7-9,000 people are diagnosed with a neuroendocrine tumor in the United States each year and the incidence is on the rise. Neuroendocrine tumors are often diagnosed at an advanced stage because they cause few symptoms until they reach a fairly large size.

A total of 28 patients with various subtypes of metastatic neuroendocrine tumors were treated as part of the study. All patients had so-called well or moderately differentiated tumors, which account for most cases of neuroendocrine tumors. All patients’ diseases had either progressed despite standard therapy with high-dose octreotide or they were ineligible for this treatment based on a negative octreotide scan.

Nearly all patients experienced clinical benefit from CAPTEM: it caused tumor shrinkage in 43% of patients overall and stalled tumor growth in 54% of patients. Importantly, high response rates were observed in carcinoid and pituitary tumors, two very difficult-to-treat neuroendocrine tumor subtypes. Among the 12 patients with carcinoid tumors, 41% had tumor shrinkage; this finding is particularly striking since the typical response rate to chemotherapy for these patients is 0-4%.

And among the four patients with pituitary tumors resistant to radiation therapy, chemotherapy, and surgery, two had complete remissions with CAPTEM, one had a 75% reduction in tumor size, and one has had stable disease for five years. At the latest data analysis, the median progression-free survival was close to 30 months, and more than four years for 25% of patients. The median overall survival was greater than 25 months.

CAPTEM combines two chemotherapy drugs: capecitabine and temozolomide. Because neorendocrine tumors grow slowy, they are frequently resistant to chemotherapy. In lab studies of neuroendocrine tumor cells researchers discovered that 5-fluorouracil (5-FU) (a drug closely related to capecitabine) enhanced temozolomide’s anticancer activity three fold. With this insight, the researchers thoughtfully selected the doses and the order in which the two drugs are given to patients (capecitabine first, temozolomide second) to maximise the efficacy of the combination regimen. The prior oral 5-FU chemotherapy depletes thymidine stores which improves the temozolomide anti-tumor effect two-to-four-fold, according to Dr. Fine.

Dr. Fine stated that patients with neuroendocrine tumors should be able to get access to both temozolomide and capecitibine fairly easily, and insurance would likely cover the cost as there is scientific evidence supporting their use as single agents in this setting. In the meantime, his research team is working on ways to make CAPTEM even more effective (such as combining it with drugs that block the platelet-derived growth factor [PDGF] pathway). As temozolomide is a major treatment option for brain cancers and melanoma, Dr. Fine would like to have the regimen tested in brain tumors and melanoma.

 

Source: eCancer News: http://ecancer.org/news/5101-asco-gi--new--rationally-based-chemotherapy-combination-appears-highly-effective-in-patients-with-treatment-resistant-neuroendocrine-tumors.php

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