Lexicon Pharmaceuticals Reports Positive Top-Line Results for Pivotal Phase 3 Telotristat Etiprate Study in Cancer Patients with Carcinoid Syndrome

“Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that the pivotal TELESTAR Phase 3 clinical trial met its primary endpoint, showing the benefit of oral telotristat etiprate in treating cancer patients with carcinoid syndrome that is not adequately controlled by the current standard of care. Telotristat etiprate was discovered using Lexicon’s gene science, based on Nobel Prize-winning technology, and is the company’s first discovery to complete a pivotal Phase 3 clinical trial. If approved, telotristat etiprate would be the first oral treatment successfully developed for carcinoid syndrome and the first addition to the standard of care in more than 16 years.

“Top-line results from the Phase 3 study show that patients who added telotristat etiprate to the standard of care at both the 250 mg and 500 mg doses experienced a statistically significant reduction from baseline compared to placebo in the average number of daily bowel movements over the 12-week study period (p<0.001), meeting the study’s primary endpoint.

“ ‘We are extremely pleased with these top-line results,’ said Lexicon President and Chief Executive Officer Lonnel Coats. ‘Carcinoid syndrome is severely debilitating, preventing many patients from leading active and predictable lives, and unfortunately, a majority of patients will not be adequately controlled over time with the current standard of care. We are committed to working closely with the FDA to file our first new drug application (NDA) and to bring this innovative new treatment to patients whose lives are already impacted by the challenges of cancer.’ “


Lung NETs and Their Treatment


Cancers that arise in the lung are mostly of the type known as NSCLC (non-small cell lung carcinoma). A much smaller proportion of lung tumors arise from neuroendocrine cells in the lungs. These cells (which are also found in most other organs) secrete a variety of hormones that are necessary for normal organ function, as well as for healing after injury or infection. Like other lung cells, neuroendocrine cells may transform to become cancers. Lung cancers that arise from neuroendocrine cells are called pulmonary neuroendocrine tumors (NETs), or lung NETs. Continue reading…


OncoBriefs: Local Tx for mRCC, Cervical Ca Prevention (CME/CE)

Editor’s note: This article describes three separate new findings in cancer research. The first is relevant for people with metastatic renal cell carcinoma (mRCC). Researchers have found that image-guided local ablation of tumors still has an important treatment role, even though there have been recent improvements in mRCC drugs. The second finding concerns people with metastatic neuroendocrine tumors (NETS). A clinical trial with volunteer patients found promising results for patients treated with the new drug lanreotide (aka Somatuline). The third finding has to do with preventing cervical cancer in women at high risk for the disease. The women involved in the study had high-grade cervical intraepithelial neoplasia (CIN 2/3), and were treated with surgical removal of the squamocolumnar junction (SCJ). These women had only low-grade recurrences, suggesting that removing SCJ cells might help prevent cervical cancer.

“More than 80% of patients with metastatic renal cell carcinoma (mRCC) remained alive without disease progression 3 years after image-guided local ablation of tumors, a retrospective study showed.

“Six of 76 evaluable tumors recurred an average of 1.6 years from treatment. Local ablation represents a “relatively safe procedure with acceptable local control rates,” authors concluded in an article published in the August issue of the Journal of Urology. A summary of the article leads off this edition of OncoBriefs, which also examines a somatostatin derivative for neurendocrine tumors and a surgical approach to cervical cancer prevention.”


Neutrophil Extracellular Traps Sequester Circulating Tumor Cells and Promote Metastasis

“The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets.”


Neutrophil Extracellular Traps Sequester Circulating Tumor Cells and Promote Metastasis

“The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets.”


Neutrophil Extracellular Traps Sequester Circulating Tumor Cells and Promote Metastasis

“The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets.”