Eduardo Davila, PhD, Assistant Professor of Pediatrics, Microbiology, and Immunology at LSU Health Sciences Center New Orleans School of Medicine and Stanley S. Scott Cancer Center, has been awarded a $1.3 million grant over five years by the National Cancer Institute of the National Institutes of Health to develop new immunotherapies, including a vaccine, for cancer. Two years of the research will be supported by the American Recovery and Reinvestment Act (ARRA).

Dr. Davila’s research lab has been working with T lymphocytes, immune cells, which can detect cancer. The LSUHSC research team has identified a novel signaling pathway in T lymphocytes, and they have demonstrated that the stimulation of specific proteins called toll-like receptors (TLRs) on the surface of human T lymphocytes boosts the production of molecules involved in tumor destruction. They have shown that TLRs can induce potent and long-lived anti-tumor activity against a highly aggressive melanoma tumor.

“One arm of this grant is looking at generating/optimizing a cancer vaccine against melanoma and breast cancer,” notes Dr. Davila. “Our preclinical data have indicated very promising results showing that we can activate and sustain high numbers of tumor-specific immune cells. Data using human cells parallel these studies and demonstrate the ability to activate human cells indicating promise in treating cancer patients.”

The LSUHSC researchers are working to increase our understanding of the underlying mechanisms of TLR activation and to define strategies to maintain potent TLR signals in T cells with the aim of prolonging antitumor T cell responses.

“We envision these studies will make possible new approaches for the development of effective T lymphocyte-based therapies against cancer through a greater understanding of molecular signals that enhance T cell activation to weakly immunogenic tumors in patients,” says Dr. Davila. “These are the tumors that grow aggressively because the body’s immune response to them is weak.”

The ARRA funding is supporting the retention of a research technician and a postdoctoral fellow in Dr. Davila’s laboratory, as well as the creation of one new position.

Source:
Leslie Capo

Louisiana State University Health Sciences Center

The U.S. fda.gov/” rel=”nofollow”>Food and Drug Administration (FDA) has approved Onsolis (fentanyl buccal soluble film). This new and patented product is indicated for the management of breakthrough pain in cancer patients who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Onsolis uses a unique delivery system designed to give rapid and reliable delivery of fentanyl. The product consists of a small dissolvable disc for application of fentanyl to the buccal (inner lining of cheek) membranes. The product is unique and offers an important step to a better pain treatment of cancer patients.

“I’m very pleased that Onsolis has been approved for marketing in the U.S. For Meda in the U.S., we get yet another important product addition. The interest among specialists for this new technology is significant, and we are making preparations for product launch during the fourth quarter of 2009. The registration procedures for Onsolis in other key markets are progressing according to plan”, said Anders Lonner, CEO Meda.

Meda has, in close collaboration with the FDA and Meda’s development partner BioDelivery Sciences Inc, developed the REMS (Risk Evaluation and Mitigation Strategy) program for Onsolis. This REMS program has also been approved by the FDA.

Source
MEDA AB

HOUSTON, July 17 — Thalidomide failed to improve survival in small cell lung cancer (SCLC) when added to chemotherapy and significantly increased the risk of venous thromboembolism (VTE), British investigators reported.

• Explain to patients that adding thalidomide to chemotherapy did not improve survival and increased the risk of thrombotic events in patients with small cell lung cancer.
• Thalidomide is not approved for the treatment of lung cancer.

Median overall survival was 10.5 months with placebo and 10.1 months with thalidomide according to Siow Ming Lee, MD, PhD, of University College Hospital in London, and colleagues.

Progression-free survival also was similar between groups, they reported in the July 16 issue of the Journal of the National Cancer Institute.

Patients with early-stage disease did not benefit from thalidomide, and those with advanced disease appeared to do worse with the antiangiogenic agent.

“Together, these results suggest that targeting antiangiogenesis in SCLC may not work as well as in multiple myeloma or colorectal cancer, perhaps because of differences in the angiogenic pathways involved in SCLC,” the researchers concluded.

The findings remained unchanged from those reported at the International Association for the Study of Lung Cancer world congress in 2007. (See Hopes Dashed for Thalidomide for SCLC)

The rationale for the study came from several lines of evidence suggesting that angiogenesis has a key role in small cell lung cancer:

• Tumor expression of vascular endothelial growth factor receptor (VEGFR)-2 and 3 and elevated serum levels of VEGFR-4
• Elevated pretreatment levels of VEGF and basic fibroblast growth factor predict poor response to chemotherapy and worse survival
• Increased vascularity of SCLC compared with non-SCLC

Previous studies had shown a high response rate and improved survival when thalidomide was given with chemotherapy, the authors said. Data from preclinical studies suggested thalidomide has synergistic activity when added to a platinum compound.

Given that background, the investigators randomized 724 patients with SCLC to receive placebo or thalidomide 100 to 200 mg daily for as long as two years. All patients received etoposide-carboplatin chemotherapy for a maximum of six three-week cycles.

The principal endpoints were overall survival, progression-free survival, tumor response rate, toxicity, and quality of life.

After a median follow-up of 37 months, the data showed no difference in overall survival between treatment groups (HR 1.09, 95% CI 0.93 to 1.27).

Median progression-free survival in both groups was 7.6 months, and at one and two years was nearly identical. Tumor response rates also did not differ.

Half the patients in the study had limited disease at enrollment and half had advanced disease. Median survival for patients with limited disease was 12.1 months with placebo and 13.1 months with thalidomide.

Patients with extensive disease fared worse with thalidomide, with a median survival of 8.0 months versus 9.1 months in the placebo group (HR 1.36, 95% CI 1.10 to 1.68).

The authors noted three possible reasons for poorer survival in patients with extensive disease who were treated with thalidomide: “thalidomide could have accelerated lung cancer progression in patients with extensive disease; it is possible that some of the deaths were incorrectly recorded as being due to lung cancer but were due to a thrombotic event or another adverse effect; or chance alone.”

Thalidomide doubled the risk of VTE, including pulmonary embolism and deep-vein thrombosis (19% versus 10%, HR 2.13, 95% CI 1.41 to 3.20, P<0.001). Most of the difference emerged during the first six months.

Adverse event rates were similar in the two groups, as was grade 3-4 hematologic and nonhematologic toxicity.

The study was funded by Cancer Research UK. Thalidomide and placebo capsules were provided free of charge by Pharmion. The authors reported no financial disclosures.

Prima

Tags: Growth Factor Receptor, International Association For The Study Of Lung Cancer, Siow Ming Lee

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