On April 4, 2016 The National Cancer Institute (NCI), part of the National Institutes of Health, reported a Blue Ribbon Panel of scientific experts, cancer leaders, and patient advocates that will inform the scientific direction and goals at NCI of Vice President Joe Biden’s National Cancer Moonshot Initiative (Press release, US NCI, APR 4, 2016, View Source [SID:1234510392]). The panel will serve as a working group of the presidentially appointed National Cancer Advisory Board (NCAB) and will provide scientific guidance from thought-leaders in the cancer community.

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"This Blue Ribbon Panel will ensure that, as NIH allocates new resources through the Moonshot, decisions will be grounded in the best science," said the Vice President. "I look forward to working with this panel and many others involved with the Moonshot to make unprecedented improvements in prevention, diagnosis, and treatment of cancer."

Over the next several months, the panel will consider how to advance the themes that have been proposed for the initiative. The themes include the development of cancer vaccines, highly sensitive approaches to early detection, advances in immunotherapy and combination therapies, single-cell genomic profiling of cancer cells and cells in the tumor microenvironment, enhanced data sharing, and new approaches to the treatment of pediatric cancers.

In addition, the cancer community, including the American public, will be provided a forum to post comments and insights to help inform the panel’s deliberations. Findings of the panel will be reported to the NCAB, which in turn will make its recommendations to NCI and contribute to the overall approach of the initiative.

"Thanks to advances in science, we are now in a historically unique position to make profound improvements in the way we treat, detect, and prevent cancer," said NIH Director Francis S. Collins, M.D., Ph.D. "The Vice President’s deep personal commitment to this noble cause will make a tremendous difference in our ability to lift the terrible burden of cancer. His call to action, including the establishment of this panel, comes at just the right time for all the right reasons."

"The Vice President’s enthusiasm about this effort is welcomed by the community of researchers, health professionals, and patients who share his passion and belief that great things are possible by accelerating cancer research with leadership and resources," said NCI Acting Director Douglas Lowy, M.D. "We are committed to breaking down silos and stimulating the groundbreaking work already underway. To be successful, we must hear a broad range of perspectives to take full advantage of the exceptional current opportunities in cancer research."

The Blue Ribbon Panel members represent a spectrum of scientific areas, including biology, immunology, genomics, diagnostics, bioinformatics, and cancer prevention and treatment. Scientific members also include investigators with expertise in clinical trials and cancer health disparities. Importantly, the members of cancer advocacy groups and pharmaceutical and biotechnology companies will be represented on the panel and its working groups.

The members of the Blue Ribbon Panel are:

Tyler Jacks, Ph.D. (Co-Chair)
Chair, National Cancer Advisory Board, and Director, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge

Elizabeth Jaffee, M.D. (Co-Chair)
Professor and Deputy Director for Translational Research, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore

Dinah Singer, Ph.D. (Co-Chair)
Acting Deputy Director and Director, Division of Cancer Biology, National Cancer Institute, Bethesda, Maryland

Peter Adamson, M.D.
Professor and Director, Experimental Therapeutics in Oncology, The Children’s Hospital of Philadelphia

James Allison, Ph.D.
Professor and Chair of Immunology, University of Texas MD Anderson Cancer Center, Houston

David Arons, J.D.
Chief Executive Officer, National Brain Tumor Society, Newton, Massachusetts

Mary Beckerle, Ph.D.
CEO and Director, Huntsman Cancer Institute, Salt Lake City

Mitch Berger, M.D.
Professor and Chair, Department of Neurological Surgery, University of California, San Francisco

Jeff Bluestone, Ph.D.
Executive Vice Chancellor and Provost, University of California, San Francisco

Mikael Dolsten, M.D., Ph.D.
President, Pfizer Worldwide Research and Development, and Executive Vice President, Pfizer, Inc., New York

James Downing, M.D.
President and CEO, St. Jude Children’s Research Hospital, Memphis, Tennessee

Levi Garraway, M.D., Ph.D.
Associate Professor of Medicine, Harvard Medical School, and Assistant Professor of Medicine, Dana-Farber Cancer Institute, Boston

Gad Getz, Ph.D.
Director, Cancer Genome Computational Analysis Group, Broad Institute of MIT and Harvard, Cambridge, Massachusetts

Laurie Glimcher, M.D.
Professor of Medicine and Dean, Weill Cornell Medical College, and Incoming President and CEO, Dana-Farber Cancer Institute, Boston

Lifang Hou, M.D., Ph.D.
Associate Professor of Preventive Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago

Neal Kassell, M.D.
Professor of Neurosurgery, University of Virginia, Charlottesville

Maria Elena Martinez, Ph.D.
Professor of Family Medicine and Public Health, Reducing Cancer Disparities Program, UC San Diego Moores Cancer Center

Deborah Mayer, Ph.D., R.N.
Professor of Adult and Geriatric Health, University of North Carolina School of Nursing, and Director of Cancer Survivorship, UNC Lineberger Comprehensive Cancer Center, Chapel Hill

Edith Mitchell, M.D., F.A.C.P
Professor of Medical Oncology and Associate Director for Diversity Services, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia

Augusto Ochoa, M.D.
Professor of Pediatrics and Director, Stanley S. Scott Cancer Center, Louisiana State University, New Orleans

Jennifer Pietenpol, Ph.D.
Professor of Biochemistry and Director, Vanderbilt-Ingram Cancer Center, Nashville

Angel Pizarro, M.S.E.
Technical Business Development Manager, Amazon Web Services Scientific Computing and Research Computing, Philadelphia

Barbara Rimer, Dr.P.H.
Alumni Distinguished Professor and Dean, University of North Carolina Gillings School of Global Public Health, Chapel Hill

Charles Sawyers, M.D.
Chair, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, and Investigator, Howard Hughes Medical Institute, New York

Ellen Sigal, Ph.D.
Founder and Chair, Friends of Cancer Research, Washington, DC

Patrick Soon-Shiong, M.B.B.Ch.
Founder, Chair, and CEO, NantWorks LLC, Los Angeles

Chi Van Dang, M.D., Ph.D.
Professor of Medicine and Director, Abramson Cancer Center, University of Pennsylvania, Philadelphia

Wai-Kwan Alfred Yung, M.D.
Professor of Neuro-Oncology and Chair of Clinical Cancer Care, University of Texas MD Anderson Cancer Center, Houston

The NCAB will advise the NCI director based on its consideration of the Blue Ribbon Panel’s recommendations, expected to be delivered later this summer. A final report by the White House Cancer Moonshot Task Force, chaired by Vice President Biden, will be produced and delivered to President Barack Obama by Dec. 31, 2016.

To meet its milestones, the panel will begin its work immediately, convening its first meeting in the coming weeks. The panel will also consider public comments over the next several months prior to making its recommendations.

Members of the research community and the public can engage in the initiative initially by subscribing to updates on the initiative’s main website (www.cancer.gov/moonshot-cancer-initiative) or by emailing the panel at [email protected]. In addition, an online forum for submitting scientific ideas and comments to the panel will be available on the site in the coming weeks.

Many patients with acromegaly do not achieve biochemical control with first-generation somatostatin analogues. A large, multicenter, randomized, Phase III core study demonstrated that pasireotide LAR had significantly superior efficacy over octreotide LAR. This analysis explores the efficacy and safety of switching therapeutic arms in inadequately controlled patients during a 12-month crossover extension.
Patients with inadequate biochemical control (GH ≥2.5 μg/L and/or IGF-1 > ULN) at end of core study (month 12) were eligible to switch to pasireotide LAR 40 mg/28 days (n = 81) or octreotide LAR 20 mg/28 days (n = 38). One dose escalation to pasireotide LAR 60 mg/28 days or octreotide LAR 30 mg/28 days was permitted, but not mandatory, at month 17 or 20.
Twelve months after crossover, 17.3 % of pasireotide LAR and 0 % of octreotide LAR patients achieved GH <2.5 μg/L and normal IGF-1 (main outcome measure); 27.2 and 5.3 % of pasireotide LAR and octreotide LAR patients achieved normal IGF-1, respectively; 44.4 and 23.7 % of pasireotide LAR and octreotide LAR patients achieved GH <2.5 μg/L, respectively. Mean (±SD) tumor volume further decreased from the end of the core study by 25 % (±25) and 18 % (±28); 54.3 % of pasireotide LAR and 42.3 % of octreotide LAR patients achieved significant (≥20 %) tumor volume reduction during the extension. The safety profile of pasireotide LAR was similar to that of octreotide LAR, with the exception of the frequency and degree of hyperglycemia-related adverse events.
Pasireotide LAR is a promising treatment option for patients with acromegaly inadequately controlled with the first-generation somatostatin analogue octreotide LAR.
clinicaltrials.gov, NCT00600886 . Registered 14 January 2008.

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Introduction E7820 is an orally administered sulfonamide that inhibits alfa-2-integrin mRNA expression. Pre-clinically E7820 showed tumor anti-angiogenic effects in various tumor cell lines and xenograft mouse models. Human daily dosing of 100 mg QD had previously been shown to be safe and tolerable. Methods The study consisted of two parts: Part A (food effect) and Part B (determination of maximum tolerated dose (MTD) for bi-daily (BID) dosing). E7820 dosing started at 50 mg BID with planned escalation to 60, 80 and 100 mg BID every 28 days. Results Fifteen patients were enrolled in Part A and 26 in Part B. The most frequent adverse events of all grades were constipation, diarrhea, nausea, and fatigue while anemia, neutropenia, and fatigue were most frequent grade ≥3 toxicities. At dose-level 60 mg BID, two patients experienced dose-limiting toxicities (grade 3 neutropenic sepsis and grade 4 neutropenia). Therefore the recommended dose (RD) was 50 mg BID. Food had no effect on E7820 exposure. E7820 exposure following twice daily administration was dose-proportional. Expression of platelet integrin-α2 measured as a response biomarker in Part B, generally decreased by a median 7.7 % from baseline following treatment with 50 mg BID E7820. Reduction was most pronounced within 1-week post treatment. The median duration of treatment was median 54, range 20-111 days. The best overall response in any treatment group was stable disease (SD): 23.1 % in Part A (100 mg QD); at the RD 66.7 % (12 of 18 patients) and 40 % in the 60 mg BID group in Part B.
Food had no effect on E7820 exposure. A dose of 50 mg BID was considered the MTD. Treatment with E7820 is safe and tolerable with 2/3 of patients (66.7 %) at MTD having SD as their best response.

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Methotrexate (MTX) is one of the most widely used medications to treat rheumatoid arthritis (RA), and recent studies have also suggested the potential benefit of the drug for the treatment of osteoarthritis (OA) of the knee. MTX is commonly administered in oral formulations, but is often associated with systemic adverse reactions. In an attempt to address this issue, we have shown previously that a conjugate of hyaluronic acid (HA) and MTX exhibits potential as a drug candidate for intra-articular treatment of inflammatory arthritis. In this study, we compare the efficacy and safety of an optimized HA-MTX conjugate, DK226, with that of MTX in inflammatory arthritis rat models.
In vitro activity of DK226 was assessed in human fibroblast-like synoviocytes (HFLS) and a synovial sarcoma cell line, SW982. Release of MTX from DK226 was investigated after incubation with rabbit synovial tissue homogenate or synovial fluid. In vivo efficacy of DK226 was evaluated in antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA) in the rat knee. Pharmacokinetics and hematological toxicity after treatment with oral MTX or an intra-articular injection of DK226 were compared in AIA.
Proliferation of HFLS and SW982 cells was inhibited by DK226, and the inhibitory activity was reversed by cotreatment with excess HA or anti-CD44 antibody. MTX was released from DK226 by incubation with rabbit synovial tissue homogenate or synovial fluid at pH 4.0, but not at pH 7.4. AIA was ameliorated by intra-articular DK226, but not by HA, as potently as oral MTX. Hematological toxicity was induced by oral MTX, but not by DK226. The maximum plasma concentration of MTX after oral MTX was 40 times higher than the concentration of MTX after an intra-articular injection of DK226. Knee swelling in AIA was inhibited by intra-articular injections of DK226, but not by free MTX or a mixture of HA and MTX. In CIA, an injection of DK226 into the right knee joint significantly reduced swelling and synovial inflammation of the treated knee joint, but had no effect on the untreated contralateral knee joint.
DK226 exerted anti-arthritic effects in two different models of arthritis. The conjugate had a wider therapeutic window than oral MTX, and could be a future drug for treatment of arthritic disorders, including inflammatory OA.

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Results from studies assessing the association between anticholinergic use and falls are mixed, and prior studies are limited in their ability to control for important potential confounders. Thus, we sought to examine the association between anticholinergic medication use, including over-the-counter medications, and recurrent falls in community-dwelling older women.
We analyzed data from a prospective cohort study of women aged 65 to 79 years from the Women’s Health Initiative Observational Study and Clinical Trials. Women were recruited between 1993 and 1998, and analyses included 61,451 women with complete information. Medications with moderate or strong anticholinergic effects were ascertained directly from drug containers during face-to-face interviews. The main outcome measure was recurrent falls (≥2 falls in previous year), which was determined from self-report within 1.5 years subsequent to the medication assessment.
At baseline, 11.3 % were using an anticholinergic medication, of which antihistamines (commonly available over-the-counter) were the most common medication class (received by 45.2 % of individuals on anticholinergic medication). Using multivariable GEE models and controlling for potential confounders, the adjusted odds ratio for anticholinergic medication use was 1.51 (95 % CI, 1.43-1.60) for recurrent falls. Participants using multiple anticholinergic medications had a 100 % increase in likelihood of recurrent falls (adjusted odds ratio 2.00, 95 % CI 1.73-2.32). Results were robust to sensitivity analysis.
Anticholinergic medication use was associated with increased risk for recurrent falls. Our findings reinforce judicious use of anticholinergic medications in older women. Public health efforts should emphasize educating older women regarding the risk of using over-the-counter anticholinergics, such as first-generation antihistamines.

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