運動降低乳癌致死率(9%: ER-/ 50% ER+) !!

Exercise Alterations of the Host–Tumor Interaction ASCO MAY 31, 2015 Dr. Lee W. Jones Lee W. Jones, PhD The putative benefits of regular exercise on both the primary and secondary prevention of major chronic conditions such as heart disease, stroke, and type II diabetes are established. As a result, recommendations to increase regular exercise are viewed as being of equal importance in the prevention and treatment of the most common chronic diseases as smoking cessation, maintaining a body mass index (BMI) of less than 25 kg/m2, and consuming a balanced diet.1 

Role of Exercise in Cancer Prevention and Prognosis  In contrast, the notion that exercise may prevent the incidence of certain forms of cancer has not gained the same level of clinical acceptance. The underlying reasons for these differences are not clear; however, there is convincing observational evidence that participation in regular exercise is associated with a 30%-50% reduction in the primary incidence of colon and breast cancers, as well as a 10%-30% reduction in the risk of other common cancers, such as prostate and lung cancers.2 Similarly, researchers have only recently begun investigating whether modifiable host factors influencing energy balance, such as body size, diet, and physical activity and exercise, are associated with cancer outcomes post-diagnosis.3,4 Regarding the latter, several observational studies suggest that, in general, regular exercise is associated with a 10%-50% reduction in the risk of recurrence, as well as cancer-specific death, even after adjustment for confounding factors, such as BMI, age, and adjuvant therapy.5,6 The majority of work has been performed in early-stage breast cancer, but initial evidence also exists in early colorectal, prostate, and ovarian cancers.5,6 Together, these data have led to a growing consensus that exercise exposure after a cancer diagnosis may alter cancer outcomes, fueling calls to action for confirmatory phase III randomized trials.4,7 Indeed, at least one such trial is ongoing. The Colon Health and Life-Long Exercise Change (CHALLENGE) trial is a phase III trial investigating the effects of regular exercise on recurrence and cancer-specific mortality in patients with postoperative colorectal cancer.8 The results of this trial are eagerly anticipated and will provide new insights into the efficacy of exercise to alter the clinical course of disease progression. In conjunction with such efforts, similar to the development of new anticancer agents, a thorough understanding of the biological properties and identification of the optimal dose, as well as predictive biomarkers to inform patient selection, will optimize the therapeutic benefit of exercise as adjuvant therapy. The following is a brief overview of emerging data in this area. 

Key Points  There is emerging evidence that compared to inactivity, higher levels of exercise following diagnosis may be associated with improvements in cancer outcomes in patients with operable breast, prostate, and colorectal cancers. Exercise may alter the events underlying cancer initiation and/or progression via the modulation of circulating growth factors and other cell phenotypes representing metabolic, sex-steroid, immune-inflammatory, and oxidative pathways that comprise the systemic host milieu. Tumor response to exercise treatment will likely be highly contingent on the tumor molecular landscape, similar to therapeutic response to pharmacologic anticancer agents. 

Biology of Exercise  Exercise is planned activity requiring the sustained activation of skeletal muscle with the objective of improving health or fitness. Adenosine triphosphate is required to maintain muscular work in response to exercise, resulting in the mobilization and breakdown of intramuscular and extramuscular substrates (e.g., carbohydrates and fat) in combination with the delivery of oxygen (from the atmosphere via the organ components of oxygen transport) to match the muscle metabolic requirements during prolonged exercise.9 The complex, coordinated multi-organ response that controls and regulates the physiological response to exercise has been summarized by several excellent reviews.10-12 In brief, repeated muscle contraction in response to chronic, repeated exercise stimuli leads to the activation of a multitude of gene-expression pathways promoting several local adaptive physiological responses. Intriguingly, these local physiologic adaptations may represent primary events that, in turn, initiate a complex cascade of subsequent local and systemic events that profoundly modulate whole-body (host) physiology and host milieu. 

Exercise Modulation of the Systemic (Host) Milieu: Is Muscle a Key Link?  The prevailing model is that exercise may alter the events underlying cancer initiation and/or progression via the modulation of circulating growth factors and other cell phenotypes representing metabolic, sex-steroid, immune- inflammatory, and oxidative pathways that comprise the systemic host milieu.13 In this realm, most research to date has focused on the role of exercise in modulating circulating metabolic factors. Skeletal muscle is the major tissue responsible for insulin-stimulated glucose uptake and fat oxidation and accounts for approximately 80% of glucose disposal under insulin-stimulated conditions; exercise can increase glucose uptake 20-100–fold in the muscle via insulin-independent mechanisms.14 Consequently, increased exercise-induced glucose disposal is critical to maintaining normal whole-body metabolic homeostasis, but it also improves metabolic control among individuals with abnormal glucose control.15  In cancer, elevated circulating levels of glucose, insulin, and insulin-like growth factors are associated with a higher primary risk of certain forms of cancer, as well as poorer prognosis after a cancer diagnosis.16 As such, the well-established ability of chronic exercise, particularly endurance training, to favorably modulate the metabolic profile in the peripheral circulation is likely an important mechanism underlying the exercise–cancer relationship. Unfortunately, this hypothesis has not been directly tested, and the limited number of clinical studies examining the effects of exercise on changes in circulating metabolic factors in patients with or at risk of cancer are mixed.5  Surprisingly little is known about the effects and molecular mechanisms of exercise-induced regulation of the other cancer-implicated host pathways.17 Such effects are likely governed by a highly integrative, complex cascade of signaling events involving numerous positive and negative reciprocal feedback loops between numerous organ systems, orchestrated via instructive signals delivered in the host bloodstream.  Primary events instigated in the skeletal muscle action may again play a critical mediating role in this process. For example, recent discoveries indicate that in response to chronic exercise, skeletal muscle operates as an endocrine organ, secreting various factors both locally and into the host circulation. In this way, skeletal muscle exerts endocrine and autocrine effects within other organs, including the brain, liver, bone marrow, pancreas, and adipose tissue (i.e., muscle-organ crosstalk).18 Such effects not only likely influence the release of factors from these distant organs, thus altering the nature and concentration of circulating factors in the systemic milieu, but also may directly modify the tissue microenvironment (niche) of these organs. This latter effect could play a role in recurrence because distant organs that may engage in crosstalk with muscles could harbor disseminated cancer cells; exercise-induced changes in the systemic milieu could, in turn, alter ligand availability in distant organ (metastatic) niches to potentially affect escape from dormancy19 and/or progression of overt metastases. Although potentially exciting, such a concept remains pure speculation at present and one that will require transdisciplinary research efforts to address. 

Are Tumor Subtypes Important?  Research investigating the mechanisms by which exercise may prevent primary or secondary cancer incidence has, to date, focused exclusively on modulation of circulating factors in the peripheral (host) circulation. As an extension, it seems biologically plausible that tumor cell response, and/or response of cells in the tumor microenvironment to exercise-induced changes in host factors, will also vary dramatically based on the tumor molecular profile. A small number of initial studies have investigated whether tumor molecular features modulate the exercise response.  For example, Holmes et al. found regular exercise (i.e., approximately 150 minutes of moderate-intensity endurance exercise per week) was associated with a relative risk reduction in breast cancer death of only 9% in women with estrogen receptor–negative tumors relative to a 50% reduction in women with estrogen receptor–positive tumors.20 This finding was corroborated by Irwin et al.21 In a detailed analysis of tumor samples obtained at the time of surgical resection, Morikawa et al. found that patients who reported a level of exercise greater than or equal to 18 metabolic equivalent task–hours per week,1 whose tumors did not express CTNNB1 (b-catenin)—a key mediator of the WNT signaling pathway that plays an important role in colorectal carcinogenesis—had an adjusted hazard ratio for colorectal cancer–specific survival of 0.33 (95% CI [0.13, 0.81]) compared with patients reporting less than 18 metabolic equivalent task–hours per week.1,22 Conversely, there was no significant relationship between exercise and prognosis in patients with tumors that were positive for nuclear CTNNB1 (adjusted hazard ratio 1.07; 95% CI [0.50, 2.30]). These initial findings indicate that, perhaps unsurprisingly, tumor response to exercise will likely be highly contingent on the tumor molecular landscape, similar to therapeutic response to pharmacologic anticancer agents.  Over the past decade, the safety and benefits of exercise as an effective adjunct therapy to offset the acute and late-occurring effects of adjuvant therapy has gained increasing recognition and acceptance.23 It is now clear that a parallel line of research investigating the efficacy of exercise as primary treatment for cancer is also gaining considerable momentum. In this context, exercise may represent a promising strategy with a largely unique ability to simultaneously modulate multiple host-related pathways, and potentially therefore, modulate the host–tumor interaction. Future efforts adopting translational approaches in an attempt to disentangle the complex multifaceted interactions between exercise-induced physiological responses, the host milieu, and cancer phenotypes pose a substantial challenge but one that could produce significant dividends in the long run. 

About the Author: Dr. Jones is a researcher at Memorial Sloan Kettering CancerCenter. He has been an ASCO member for 10 years and currently serves on the Cardiac Toxicity and Survivorship committees. 

References:  

Eyre H, Kahn R, Robertson RM, et al. Preventing cancer, cardiovascular disease, and diabetes: a common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association. CA Cancer J Clin. 2004;54:190-207.

Friedenreich CM, Orenstein MR. Physical activity and cancer prevention: etiologic evidence and biological mechanisms. J Nutr. 2002;132:3456S-3464S. Goodwin PJ, Meyerhardt JA, Hursting SD. Host factors and cancer outcome. J Clin Oncol. 2010;28:4019-4021.

Ligibel JA, Alfano CM, Courneya KS, et al. American Society of Clinical Oncology position statement on obesity and cancer. J Clin Oncol. 2014;32:3568-3574.

Betof AS, Dewhirst MW, Jones LW. Effects and potential mechanisms of exercise training on cancer progression: a translational perspective. Brain Behav Immun. 2013;30:SupplS75-S87.

 Ballard-Barbash R, Friedenreich CM, Courneya KS, et al. Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104:815-840.

Ballard-Barbash R, Hunsberger S, Alciati MH, et al. Physical activity, weight control, and breast cancer risk and survival: clinical trial rationale and design considerations. J Natl Cancer Inst. 2009;101:630-643.

 Courneya KS, Booth CM, Gill S, et al. The Colon Health and Life-Long Exercise Change trial: a randomized trial of the National Cancer Institute of Canada Clinical Trials Group. Curr Oncol. 2008;15:279-285.

Jones LW, Eves ND, Haykowsky M, et al. Exercise intolerance in cancer and the role of exercise therapy to reverse dysfunction. Lancet Oncol. 2009;10:598-605.

Hawley JA, Hargreaves M, Joyner MJ, et al. Integrative biology of exercise. Cell. 2014;159:738-749.

Jones NL, Killian KJ. Exercise limitation in health and disease. N Engl J Med. 2000;343:632-641.

Coffey VG, Hawley JA. The molecular bases of training adaptation. Sports Med. 2007;37:737-763.

McTiernan A. Mechanisms linking physical activity with cancer. Nat Rev Cancer. 2008;8:205-211.

Goodyear LJ, Kahn BB. Exercise, glucose transport, and insulin sensitivity. Annu Rev Med. 1998;49:235-261.

Stanford KI, Goodyear LJ. Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle. Adv Physiol Educ. 2014;38:308-314.

Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer. 2012;12:159-169.

 Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature. 2008;454:463-469.

Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8:457-465.

Jones LW, Antonelli J, Masko EM, et al. Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer. J Appl Physiol (1985). 2012;113:263-272.

Holmes MD, Chen WY, Feskanich D, et al. Physical activity and survival after breast cancer diagnosis. JAMA. 2005;293:2479-2486.

 Irwin ML, Smith AW, McTiernan A, et al. Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study. J Clin Oncol. 2008;26:3958-3964.

Morikawa T, Kuchiba A, Yamauchi M, et al. Association of CTNNB1 (beta-catenin) alterations, body mass index, and physical activity with survival in patients with colorectal cancer. JAMA. 2011;305:1685-1694.

Jones LW, Alfano CM. Exercise-oncology research: past, present, and future. Acta Oncol. 2015;52: 195-215.

Straussman R, Morikawa T, Shee K, et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature. 2012;487:500-504.    

離譜藥價 Martin Shkreli (CEO, Turing Pharmaceuticals)點燃藥界價值(Value)策略翻轉秘密!

Value of Medicine, Cost of Innovation and Sustainability of Current Pricing Strategies: What to expect next? Arda Ural, MSc, MBA, PhD Managing Director, Accenture Strategy Life Sciences  Oct 5, 2015  Recent news about a small specialty pharma led by a former hedge fund manager, who increased the price of a 60-plus-year-old taxoplasmosis drug used mostly by HIV patients, from $13.5 per pill to $750 per pill evaporated billions of dollars of value from the entire biotechnology sector and put the spotlight –once again- on value of medicines, the price of innovation and ultimately the sustainability of the strategy of shifting portfolios to specialty therapeutics and rare diseases with supposedly inelastic pricing. 

Pricing Debate Brewing  The first round of the pharma pricing debate was brought forth last December when AbbVie and Express Scripts stroke a pricing deal for Viekira Pak over Gilead's Sovaldi in exchange for exclusive access. At $84,000 per treatment towards a likely 'cure' and full eradication of the Hep C virus, the health economics case was relatively well-established given lack of any alternative treatments to stop the progression of the disease leading up to liver transfer or death. Since then valuation-wise both companies did phenomenally well while thousands of Hep C patients gained their health back, which was previously unimaginable.  Next, we saw several hundreds of thousands of dollars price tags for rare disease medications which helped valuations of a handful of biotech companies push to unjustifiable levels despite the fact that they have only one or two such medications in the market or in the pipeline.  It took the industry several decades (and a massive –existential- patent cliff) to realize the niche market opportunity and introduce 500 products according to provisions outlined in the Orphan Drug Act of 1983 that provides 7 years of market exclusivity. 

Shifting Product Mix to Specialty and Rare Disease  As the product mix of pharma companies continue to pivot to specialty medicine we should expect that this debate is only to get more relevant. According to Bloomberg, 27 branded drugs showed "price gains of at least 20 percent in typical dosages since the first quarter of 2014," and over the past five years, "prices of dozens of drugs doubled or more while the Consumer Price Index rose only 9 percent."  The overall drug cost within the total healthcare spend remains about 10% over the years enabled by the expiring intellectual property protection of former blockbusters. However, once this transient effect is over, and with the shifting product mix towards specialty/rare disease portfolios, we should expect this share to increase to put further pressure on pharma drug pricing in the next few years. For example, prices for PCSK9 inhibitors (approximately $14,000 per year), new immuno-oncology drugs and congestive heart failure medications are all coming to market with significant price tags. Additionally, biosimilars which are expected to exert a downward pricing pressure on the entrenched monoclonal antibodies, put a modest 15% discount and chose to build their market share through investing in commercialization. 

Systemic Backlash  The current (and certainly not the last round of this) debate about drug pricing practices drew attention not only from payers, trade associations, providers, patient advocates but also aspiring presidential candidates Clinton and Sanders, who seem to continue to keep this topic as part of their campaign platforms.   In fact, there is already a backlash from the American Society of Clinical Oncologists (ASCO) preparing their own cancer drug scorecard this past summer that aims to link cancer medications' therapeutic value to their price. In the UK, a hot-bed of pharma drug price capitation, NHS's Cancer Drugs Fund have announced that they will slash prices of 17 oncology drugs from their formularies. Finally, Aetna and United have already started pushing back on their coverage of PCSK9 Inhibitors. 

 Path Forward: Expectations and Strategies  Here are three potential expectations and corresponding strategies for pharma / biotech companies to consider:   Expect more pricing scrutiny In absence of a clear solution path, several ideas will be tested including (but not limited to)  Direct Medicare / Medicaid negotiations over drug costs, Reimportation of drugs from Canada or Western Europe, Single Drug Tier 1 Formularies, Shortening the exclusivity period of orphan drugs, Accelerated regulatory frameworks for biosimilar approvals, and Lots of noise in public forums.    

Continue to Invest in Innovative Therapies informed by Precision Medicine Assuming 21st Century Cures Act will be signed by the President, it will provide the NIH and the FDA additional funding to accelerate advancement of medications to market with streamlined regulatory requirements for researchers. The legislation would allow greater use of precision medicine, including biomarkers, allowing new technology sooner and more effectively. The act also will create a structured framework to include patient experience data when reviewing drugs in FDA's decision-making.     

Test and Scale Value-driven Business Models Pharma needs to change its business proposition from ("taking high risk to develop products and deserve a decent price premium") to ("developing highly-targeted treatment modalities and taking them to market with a value-based, outcomes-focused model enabled by healthcare technologies and services.") Assuming a calculated risk appetite, there is plenty of room to design and test value-based contracting with provider systems that can be enhanced by myriad of solutions healthcare technology space will provide that can be augmented by patient services.      

Drug Goes From $13.50 a Tablet to $750, Overnight By ANDREW POLLACKSEPT. 20, 2015 Specialists in infectious disease are protesting a gigantic overnight increase in the price of a 62-year-old drug that is the standard of care for treating a life-threatening parasitic infection. The drug, called Daraprim, was acquired in August by Turing Pharmaceuticals, a start-up run by a former hedge fund manager. Turing immediately raised the price to $750 a tablet from $13.50, bringing the annual cost of treatment for some patients to hundreds of thousands of dollars."What is it that they are doing differently that has led to this dramatic increase?" said Dr. Judith Aberg, the chief of the division of infectious diseases at the Icahn School of Medicine at Mount Sinai. She said the price increase could force hospitals to use "alternative therapies that may not have the same efficacy. A demonstration last year against Gilead Sciences, whose hepatitis C drugs, which cost $1,000 a pill or more.Drug Prices Soar, Prompting Calls for JustificationJULY 23, 2015 Turing's price increase is not an isolated example. While most of the attention on pharmaceutical prices has been on new drugs for diseases like cancer, hepatitis C and high cholesterol, there is also growing concern about huge price increases on older drugs, some of them generic, that have long been mainstays of treatment.  Martin Shkreli is the founder and chief executive of Turing Pharmaceuticals, which raised the price of the drug Daraprim to $750 a tablet from $13.50. Although some price increases have been caused by shortages, others have resulted from a business strategy of buying old neglected drugs and turning them into high-priced "specialty drugs."  Cycloserine, a drug used to treat dangerous multidrug-resistant tuberculosis, was just increased in price to $10,800 for 30 pills from $500 after its acquisition by Rodelis Therapeutics. Scott Spencer, general manager of Rodelis, said the company needed to invest to make sure the supply of the drug remained reliable. He said the company provided the drug free to certain needy patients.  In August, two members of Congress investigating generic drug price increases wrote to Valeant Pharmaceuticals after that company acquired two heart drugs, Isuprel and Nitropress, from Marathon Pharmaceuticals and promptly raised their prices by 525 percent and 212 percent respectively. Marathon had acquired the drugs from another company in 2013 and had quintupled their prices, according to the lawmakers, Senator Bernie Sanders, the Vermont independent who is seeking the Democratic nomination for president, and Representative Elijah E. Cummings, Democrat of Maryland.  Doxycycline, an antibiotic, went from $20 a bottle in October 2013 to $1,849 by April 2014, according to the two lawmakers.  The Infectious Diseases Society of America and the HIV Medicine Association sent a joint letter to Turing earlier this month calling the price increase for Daraprim "unjustifiable for the medically vulnerable patient population" and "unsustainable for the health care system." An organization representing the directors of state AIDS programs has also been looking into the price increase, according to doctors and patient advocates.  Daraprim, known generically as pyrimethamine, is used mainly to treat toxoplasmosis, a parasite infection that can cause serious or even life-threatening problems for babies born to women who become infected during pregnancy, and also for people with compromised immune systems, like AIDS patients and certain cancer patients.  Martin Shkreli, the founder and chief executive of Turing, said that the drug is so rarely used that the impact on the health system would be minuscule and that Turing would use the money it earns to develop better treatments for toxoplasmosis, with fewer side effects.  "This isn't the greedy drug company trying to gouge patients, it is us trying to stay in business," Mr. Shkreli said. He said that many patients use the drug for far less than a year and that the price was now more in line with those of other drugs for rare diseases.  "This is still one of the smallest pharmaceutical products in the world," he said. "It really doesn't make sense to get any criticism for this."  This is not the first time the 32-year-old Mr. Shkreli, who has a reputation for both brilliance and brashness, has been the center of controversy. He started MSMB Capital, a hedge fund company, in his 20s and drew attention for urging the Food and Drug Administration not to approve certain drugs made by companies whose stock he was shorting.  In 2011, Mr. Shkreli started Retrophin, which also acquired old neglected drugs and sharply raised their prices. Retrophin's board fired Mr. Shkreli a year ago. Last month, it filed a complaint in Federal District Court in Manhattan, accusing him of using Retrophin as a personal piggy bank to pay back angry investors in his hedge fund.  Mr. Shkreli has denied the accusations. He has filed for arbitration against his old company, which he says owes him at least $25 million in severance. "They are sort of concocting this wild and crazy and unlikely story to swindle me out of the money," he said. Martin Shkreli, the chief executive of Turing Pharmaceuticals, explains the increase in drug prices in a CNBC interview. By CNBC on Publish Date September 21, 2015.  Daraprim, which is also used to treat malaria, was approved by the F.D.A. in 1953 and has long been made by GlaxoSmithKline. Glaxo sold United States marketing rights to CorePharma in 2010. Last year, Impax Laboratories agreed to buy Core and affiliated companies for $700 million. In August, Impax sold Daraprim to Turing for $55 million, a deal announced the same day Turing said it had raised $90 million from Mr. Shkreli and other investors in its first round of financing.  Daraprim cost only about $1 a tablet several years ago, but the drug's price rose sharply after CorePharma acquired it. According to IMS Health, which tracks prescriptions, sales of the drug jumped to $6.3 million in 2011 from $667,000 in 2010, even as prescriptions held steady at about 12,700. In 2014, after further price increases, sales were $9.9 million, as the number of prescriptions shrank to 8,821. The figures do not include inpatient use in hospitals.  Turing's price increase could bring sales to tens or even hundreds of millions of dollars a year if use remains constant. Medicaid and certain hospitals will be able to get the drug inexpensively under federal rules for discounts and rebates. But private insurers, Medicare and hospitalized patients would have to pay an amount closer to the list price.  Some doctors questioned Turing's claim that there was a need for better drugs, saying the side effects, while potentially serious, could be managed.   "I certainly don't think this is one of those diseases where we have been clamoring for better therapies," said Dr. Wendy Armstrong, professor of infectious diseases at Emory University in Atlanta.  With the price now high, other companies could conceivably make generic copies, since patents have long expired. One factor that could discourage that option is that Daraprim's distribution is now tightly controlled, making it harder for generic companies to get the samples they need for the required testing.  The switch from drugstores to controlled distribution was made in June by Impax, not by Turing. Still, controlled distribution was a strategy Mr. Shkreli talked about at his previous company as a way to thwart generics.  Some hospitals say they now have trouble getting the drug. "We've not had access to the drug for a few months," said Dr. Armstrong, who also works at Grady Memorial Hospital, a huge public treatment center in Atlanta that serves many low-income patients.  But Dr. Rima McLeod, medical director of the toxoplasmosis center at the University of Chicago, said that Turing had been good about delivering drugs quickly to patients, sometimes without charge.  "They have jumped every time I've called," she said. The situation, she added, "seems workable" despite the price increase.  Daraprim is the standard first treatment for toxoplasmosis, in combination with an antibiotic called sulfadiazine. There are alternative treatments, but there is less data supporting their efficacy.  Dr. Aberg of Mount Sinai said some hospitals will now find Daraprim too expensive to keep in stock, possibly resulting in treatment delays. She said that Mount Sinai was continuing to use the drug, but each use now required a special review.  "This seems to be all profit-driven for somebody," Dr. Aberg said, "and I just think it's a very dangerous process."

抗癌藥太貴?! ASCO 擬提供整體評估 供臨床醫師使用指導!!

ASCO Publishes Conceptual Framework to Assess the Value of New Cancer Treatment Options Framework to support shared decision-making between doctors and patients; ASCO solicits public comment FOR IMMEDIATE RELEASE: June 22, 2015 Contact: Mary Rappaport (571)-483-1374 mary.rappaport@asco.org ALEXANDRIA, Va. – The American Society of Clinical Oncology (ASCO) today published an initial version of a conceptual framework for assessing the value of new cancer treatment options based on clinical benefit, side effects, and cost. The framework will serve as the basis for user-friendly, standardized tools that doctors can use with their patients to discuss the relative value of new cancer therapies compared with established treatments."Value and cost are among the biggest issues in healthcare today, but there are few tools to help doctors and patients objectively assess benefits, side effects and costs," said ASCO President Julie M. Vose, MD, MBA, FASCO. "Our goal is to help oncologists and their patients weigh potential treatment options based on high-quality scientific evidence and a thoughtful assessment of each patient's needs and goals. In publishing this initial version of the framework, just the beginning of the process, we hope to drive discussion and debate about a critically important issue." The ASCO Value Framework, published in the Journal of Clinical Oncology, was developed by ASCO's Value in Cancer Care Task Force, with input from oncologists, patient advocates, representatives of the pharmaceutical and insurance industries, and others. ASCO is soliciting comments on the framework, which is available online at www.asco.org/value.

Cost an increasing burden for cancer patients ASCO is developing the framework at a time when patients are increasingly affected by the costs of cancer care. Costs have risen sharply in recent years, and cancer drugs are a significant driver of these increases. Newly approved cancer drugs now cost an average of $10,000 per month, with some exceeding $30,000 per month. Many patients are feeling the impact because they pay a significant share of drug costs through health insurance deductibles, co-payments, and other out-of-pocket expenses."Cancer patients are increasingly burdened by the rising costs of care," said Lowell E. Schnipper, MD, FASCO, Chair of ASCO's Value in Cancer Care Task Force. "Even well-insured patients are often unprepared for the high out-of-pocket cost of some cancer therapies. Too often, that leads to severe financial strain and even bankruptcy." Studies have also shown that some cancer patients take less medication than prescribed, or avoid filling prescriptions altogether, because of concerns about cost.

Value framework draws on high-quality evidence The ASCO Value Framework proposes a methodology to compare the relative clinical benefits, side effects, and costs of treatment regimens that have been tested head-to-head in randomized clinical trials. Data on the clinical benefits and side effects of each regimen are used to calculate a combined "Net Health Benefit" score, or NHB. The NHB represents the added benefit that patients can expect to receive from the new therapy, versus the current standard of care. The NHB is calculated based on improvement in overall or progression-free survival, and on the number and severity of toxicities. For patients with advanced cancer, a higher NHB is awarded for regimens that also offer relief from cancer-related symptoms or allow patients a treatment-free period. The framework relies on high-quality scientific evidence available from randomized clinical trials, including commonly-reported data such as clinical outcomes and toxicity. Other important measures, such as quality of life and patient-reported outcomes, are not used in the framework, because they are not reported consistently enough to be reliable. The NHB is presented alongside the patient's expected out-of-pocket costs for the regimens being compared, as well as the overall drug acquisition cost."It's critical to distinguish between value and cost," said Dr. Schnipper. "Sometimes the more valuable treatment will be the more expensive one and sometimes it won't be. Ultimately, the definition of 'value' will be highly personalized for each patient, taking into account an individual's own preferences and circumstances. For example, in the setting of advanced cancer, is length of life the most important goal or is quality of life? Is the proposed treatment affordable? That's why we're proposing to provide information on net health benefit and cost side-by-side." The framework is intended for doctors to use on an individual basis with their patients, and would not provide generalizable scores or rankings. Once the framework is finalized and adapted into a practical tool for clinical use, doctors would be able to adjust parameters based on an individual patient's health needs, preferences, and financial situation—resulting in a personalized value assessment. To help demonstrate the potential utility of the framework, the ASCO Task Force applied its methodology to four clinical scenarios: metastatic lung cancer; advanced multiple myeloma; metastatic prostate cancer; and adjuvant therapy for HER2-positive breast cancer. The results were striking: in some clinical scenarios, a newer, more expensive regimen had a much larger NHB than the previous standard. In other scenarios, the newer, more expensive regimen showed little or no net health benefit. These are sample scenarios only, and NHBs for the same regimen may vary in different types of cancer or treatment settings. ASCO emphasizes that the proposed framework is intended to empower patients with clear information, and should not be used to limit patient choice. "This framework is about weighing the options, not limiting them," said Dr. Vose. "It should not be used to replace physician judgment or patient preference."

Seeking comment from all stakeholders ASCO is soliciting feedback from all interested stakeholders on the framework's methodology and applicability. Comments may be submitted through August 21, 2015 at www.asco.org/value. Comments will inform the evolution of the value framework, which will be modified in response to feedback and updated as new data are developed about the utility and impact of new treatments in different clinical scenarios. Ultimately, ASCO plans to use the framework as the basis of physician-guided tools for day-to-day use in clinical settings. ASCO will move quickly to address input received, although the specific timeline for future steps is not yet determined.

About ASCO's Value in Cancer Care Task Force ASCO's Value in Cancer Care Task Force is comprised of physicians, patient advocates, and representatives of the insurance and pharmaceutical industries. The Task Force was established in 2007 to educate oncologists about the importance of discussing costs associated with recommended treatments, empower patients to ask questions about the anticipated costs of their treatment options, identify the drivers of the rising costs of cancer care, and develop policy positions to promote access to the highest-quality care at the lowest cost. A list of Task Force members is available at www.asco.org/value.

Related products developed by ASCO include:

ASCO Task Force Guidance on the Cost of Cancer Care, 2009 for oncology professionals/ Managing the Cost of Cancer Care for patients and families/ Cancer.Net resources for patients about the costs of cancer care

ASCO has also participated in the "Choosing Wisely" initiative, sponsored by the American Board of Internal Medicine Foundation. As part of this effort, ASCO published two "Top Five" lists of opportunities to improve quality and value in cancer care by curbing use of common tests and treatments that are not supported by clinical evidence. ASCO is also advancing payment models that reward quality of care, rather than volume, and supporting quality efforts such as the Quality Oncology Practice Initiative (QOPI) and CancerLinQ, an initiative to harness big data analytics to improve cancer care.

About ASCO Founded in 1964, the American Society of Clinical Oncology (ASCO) is the world's leading professional organization representing physicians who care for people with cancer. With more than 35,000 members, ASCO is committed to improving cancer care through scientific meetings, educational programs and peer-reviewed journals. ASCO is supported by its affiliate organization, the Conquer Cancer Foundation, which funds ground-breaking research and programs that make a tangible difference in the lives of people with cancer. For ASCO information and resources, visit www.asco.org. Patient-oriented cancer information is available at www.cancer.net. For the latest cancer-related policy developments, please visit ascoaction.asco.org.

尹啟銘: 創業拔萃方案 (具體完備) VS亞洲矽谷計畫 (空無一物)

尹啟銘／亞洲矽谷―蔡英文的夢囈  作者／尹啟銘 日前蔡英文發表所謂的「亞洲矽谷計畫」，初看之下，被它的名稱所吸引，不是因為它的新穎，而是因為它的過時；而在細閱之後，發現原來又是蔡英文的另場夢囈，空空蕩蕩，其所談不是現在政府正在推動的業務，就是根本不知所云。 蔡英文說，「我們的計畫，是一個網絡的概念，跟過去的科學園區或工業園區是不一樣的，並不是要引進大規模的製造活動，也不需要非常多的土地；我們要做的，是讓產業、學術與研究單位，能夠有適當的環境，可以彼此交流和支援，同時引進國際資源，形成一個有助於創新的交流」。 從蔡英文所說，可以知道，「亞洲矽谷計畫」只是一個雷聲大、雨點小的名詞，要做的工作只是促進交流的活動，而這些，不就是現在政府正在做的事情！ 就好像蔡英文競選政策辦公室執行長張景森所說，「亞洲矽谷計畫是以桃園作為串連北北基企業總部、軟體研發，以及新竹科技製造能量的樞紐」，其所提企業總部（內湖科技園區）、軟體研發（南港軟體園區）、新竹科技製造（新竹科學園區）不都是現在既有的產業聚落！而亞洲矽谷計畫竟然只是要以桃園將該等產業聚落串連，桃園就可以成為亞洲矽谷的中心，渠等天真之程度真是足以令人笑掉大牙！  至於蔡英文所強調的，要引進國際資源，打造「亞洲青年創新IPO中心」，實際上行政院國發會去年實施的《創業拔萃方案》就以「法規鬆綁」、「引進國際資金與專業知識」及「打造國際創新創業園區」三大策略在推進「台灣成為區域創新創業園區」的願景，要引進國內外加速器、創投、專業業師等資源，提供新創團隊一站式服務，打造正向的創業生態系統，並將透過虛擬網路，與美國矽谷、英國倫敦、新加坡等地之新創事業、投資人、育成或加速器機構等建立合作關係，內容相當具體完備，蔡英文的「亞洲矽谷計畫」與之相較，只顯空無一物，僅餘標題。 最後，之所以要挑選桃園作為亞洲矽谷計畫的執行基地，蔡英文說，「無論是在交通、人力、產業、研發體系，都具備很好的基礎，這是為什麼我們要選定桃園的原因。」說來好笑，蔡英文所舉幾個因素只是「必要條件」的一部分，別的縣市也具備，桃園未必有最強的競爭力，至於如何讓桃園成為亞洲矽谷的「充分條件」，卻完全看不到具體策略和作法，這若不是夢囈，那會是什麼！  2005年5月15日出版的美國商業周版（Business Week）曾經以「台灣為何重要？」（Why Taiwan Matters？）做為封面故事，報導指出沿著中山高速公路，從台北內湖地區，途經桃園，再到新竹，短短70公里的公路，可以說是「隱形的全球經濟中心」（hidden center of the global economy），這裡有無數的高科技公司，他們是美國資訊科技業的「動力廠」（powerhouse）；蔡英文所謂的「亞洲矽谷」，台灣早已形成，美國人10年前就已肯定，不知現今的蔡英文是否仍活在30年前的台灣？  ●作者尹啟銘，財團法人國家政策研究基金會執行長。以上言論為個人立場，與公司無關。88論壇歡迎雲友更多參與，也歡迎網友發表高見，投稿請寄editor88@ettoday.net

陳五福: 台灣產業的 生產創新/研發創新/品牌創新 (機會財/ 管理財/ 價值財)

資誠：台灣產業創新 企業要賺「價值財」資誠聯合會計師事務所所長張明輝、智融創新顧問公司董事長陳五福、神基科技董事長黃明漢、資誠企管顧問公司副董事長劉鏡清參加2015台灣投資高峰論壇之「創新論壇」場  (中央社訊息服務20151002 15:00:15)台灣八月景氣燈號持續亮藍燈，景氣仍處於低緩，另一方面紅色供應鏈席捲全球，兩岸競合局勢劇烈丕變。有鑑於此，中華民國股權協會及資誠聯合會計師事務所等企業於今天以「變遷時局逆轉勝」為題，假臺大醫院國際會議中心聯合主辦一年一度的「台灣投資高峰論壇」。在論壇上午的場次中，資誠聯合會計師事務所以「創新」為主題，邀請智融創新顧問公司董事長陳五福、神基科技董事長黃明漢及資誠企管顧問副董事長劉鏡清為與談人，探討科技創新、產業創新與制度創新，以及台灣產業創新的機遇與挑戰等議題。創新論壇主持人資誠聯合會計師事務所所長張明輝表示，競爭力是企業成功的關鍵，也是國家發展的關鍵，而國家競爭力與企業發展更是息息相關。根據PwC研究指出，在每年人均國民所得約在八千到一萬美元的國家，企業賺的是「機會財」，只要產業對，就能賺錢；所得在一萬到兩萬美元之間的國家，企業賺的是「管理財」，在競爭越來越激烈的環境中，企業要會管理且效率要高；而在所得邁向兩萬美元的國家，企業則要賺「價值財」，企業必須要能夠創新且創造價值。呼應張明輝的說法，資誠企管顧問副董事長劉鏡清接著指出，台灣的每年人均國民所得已突破兩萬美金，已經無法再談賺「管理財」或是談「提升效率」，而是應該要創造價值。從工業4.0的創新趨勢來看，傳統產業可透過數位化來降低成本，而達到產品或服務的創新。然而，台灣也必須思考如何在商業模式進行創新，要能夠建立產業的標準規格及價值鏈，必要時，透過合作的方式來進行整合，以加快商業模式創新的速度。他也呼籲台灣企業要放開心胸、打破心防，勇於跨界合作才能創造新的機會。智融創新顧問公司董事長陳五福指出，創新是「Do the right thing」，這比「Do the thing right」更加困難，但也更加重要。台灣的產業從過去的生產技術的創新，走到現階段的研發創新，但未來必須走向品牌的創新。未來，台灣要走「大確幸」而非「小確幸」，要把眼光放到全球市場，為台灣創造更高的價值。談到台灣創新的未來走向，神基科技董事長黃明漢表示，還是要回歸到人類的基本需求，包括食衣住行以及對於活得更好及活得更久的期望，因此，結合新科技的傳統產業可能是台灣未來的產業轉型新機會，例如台灣農業的企業化或是高階醫療器材等產業。  至於對政府創新政策的建言，張明輝提出五大建議方向，分別是產業要轉型、培育創新人才、獎勵創新、擴大國際市場以及政府產業政策。劉鏡清建議建立生態系統來協助創新者，並且依創新者的不同程度給予不同的輔導機制。陳五福則建議政府，對於大企業來說，只需建立適合的環境而不需太多限制，對小企業則是要引導其創新的方向。黃明漢則指出，台灣面臨產業、國際及法規制度的斷鏈，同時欠缺執行力，期許政府在上述面向能夠持續進步，打造更美好的台灣。  訊息來源：資誠聯合會計師事務所

缺錢如何把科研作好!! (科技部”盡力”幫忙??!!)

產學鏈結成果斐然 技轉金創新高 2015-10-01 16:59:30 中央社 台北1日電  科技部統計，截至目前為止，今年度技轉簽約金額逾新台幣2.7億元，創下合約授權金歷史新高，其中高醫大的單一生技研究成果技轉金就高達5億元，也創國內單筆技轉簽約金新高。2015台北國際發明暨技術交易展今天起至3日在台北世貿一館展出，科技部今年以「相乘的力量」為主題設置「科技館」，邀集30個學研機構參與，現場展出120件創新技術，展期三天共有25場發表活動。  科技部次長林一平表示，今年的科技館以「高齡化」、「城市化」、「工業化」及「氣候變遷」四大趨勢打造體驗區，科技部都會積極協助學研單位將成果移轉給業界，讓技術與發明能因應、解決當前台灣面臨的社會與環境問題。他更直接向出席開幕儀式的各學界代表喊話，把科研作好，「缺錢找科技部」，科技部會盡力幫忙。  林一平在開幕前先參觀中國科技大學展出的像「尿布偵測與預測系統」，透過建置無線感知與通訊模組，收集貼片上尿布溫度與溼度的變化，提供包括尿溼度偵測與提醒功能，目前已和4家機構合作使用。另外，還有「銀髮族日常活動監測系統」、「輔助起身及坐下之馬桶座裝置」等，能貼心地監測與照護長者的技術與發明等。在永續與環保議題，科技館今年展出獨步全球的領先技術「高安全性鋰離子電池(STOBA)」，其中，電動機車所使用的電池，不僅體積較傳統電池小1/4，且提升電池充放電速度達20%，在家就可以充電，一顆電池最長可跑50公里，相當於可從台北騎到中壢，今年已將技術導入與日本三井化學，並與鴻海與新能源集團等電池技術大廠洽談中。科技部表示，積極推動各項產學鏈結措施， 截至目前為止，今年度技轉簽約金額逾2.7億元，創下合約授權金歷史新高。  另外，今年高雄醫學大學展出的「一種可屏蔽抗體活性的閉鎖器」可提供全世界新藥主流抗體藥物能選擇性地針對患部進行治療，大大降低副作用的產生，其技轉簽約金高達5億5180萬元，分十期支付，技轉給國外廠商SEATTLE GENETICS,INC.，創國內單筆技轉簽約金新高，展現學研單位技術研發成果斐然，更是產學媒合的成功案例之一。

Leadership in antibody-drug conjugate development Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs). ADCs are empowered antibodies designed to harness the targeting ability of monoclonal antibodies by linking them to cell-killing agents. For more than 20 years, engineered monoclonal antibodies have provided therapeutic benefit to people with cancer, autoimmune diseases and other serious medical conditions. Early antibody-based therapies revolutionized the treatment of cancer by targeting malignant cells and limiting damage to normal tissue. This resulted in therapies that were better tolerated and could be used in combination with chemotherapy to improve patient outcomes without significant increases in toxicities. While engineered antibodies have provided clinical benefit in several disease indications, many antibodies lack sufficient intrinsic antitumor activity to be used as therapeutics. Seattle Genetics has developed proprietary, industry-leading technology that is the next step in therapeutic antibody-based therapies. Our ADC technology combines the specificity of engineered antibodies with the potent cell-killing effects of chemotherapy.

First FDA-Approved CD30-Directed ADC Our lead program, ADCETRIS® (brentuximab vedotin), is an ADC that, in collaboration with Takeda Pharmaceutical Company, is approved in more than 55 countries, including the U.S., Canada, Japan and members of the European Union. ADCETRIS comprises an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing our proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

Driving the Field of ADCs We are conducting significant research activities to continue advancing our ADC technology and are committed to staying the leader in ADC development. There are currently more than 20 ADCs in clinical development using our proprietary technology, including our internal and co-development programs, as well as multiple collaborator programs. In addition to ADCETRIS, our internal pipeline includes SGN-CD19A, an ADC targeting CD19, SGN-CD33A, an ADC targeting CD33, SGN-LIV1A, an ADC targeting LIV-1, SGN-CD70A, an ADC targeting CD70, as well as ASG-22ME and ASG-15ME, ADCs that we are co-developing with Agensys. In addition to our auristatin-based ADC technology, which is employed in ADCETRIS and several internal and collaborator programs, we are evaluating another ADC technology using a highly potent cytotoxic agent called a pyrrolobenzodiazepine (PBD) dimer that kills cells by a different mechanism than auristatins. The agent, currently employed by SGN-CD33A and SGN-CD70A, is stably linked to an antibody with our site-specific engineered cysteines, resulting in uniform drug-loading of two PBD dimers per antibody. We call this engineered antibody an EC-mAb. Our proprietary PBD and EC-mAb technologies illustrate our efforts to continue driving the field of ADCs.

 

長效型體抑素(Octreotide) 用於肢端肥大症&神經內分泌瘤

罕見疾病－肢端肥大症併發症多 2015年10月02日 04:09 (中國時報) 李盛雯／台北報導 一名21歲年輕男性，個子相當高大，起初因為糖尿病急性併發症而就醫，經過長時間治療，醫師發現，即使施打胰島素，血糖值也降不下來，懷疑是腦下垂體腫瘤引發的肢端肥大症作怪。林口長庚內分泌暨新陳代謝科醫師林仁德解釋，肢端肥大症由於腦下垂體長出良性腫瘤，引發生長激素（GH）分泌過量而導致相關內分泌疾病，這類患者最常見的症狀包括臉形改變、經常性頭痛、手腳變大等，關節的症狀特別明顯，也常見戴帽子的患者，一段時間後會發現帽子竟然戴不下，或手指變粗使得戒指無法拔除。肢端肥大症因為症狀進程緩慢，很難在早期找對醫師，平均要流浪5年才能確診，但延遲就醫，患者會有較高風險發生嚴重併發症，如心血管疾病、肝腫大、甲狀腺腫大等。根據臨床統計，約1/3患者在診斷時會合併有糖尿病、高血壓、頭痛及關節炎等併發症，由於這類疾病會刺激全身細胞生長，有研究發現，可能與癌症的發生有密切關係。林仁德表示，肢端肥大症會令身體各個器官都變大，也連帶讓細胞變大。經由大腸篩檢的統計發現，這類患者罹患腸息肉的機率比一般人高，而且，除了可能罹患腸癌外，甲狀腺癌及乳癌、頭頸癌等風險也高。目前肢端肥大症的第一線治療方式以手術為主；不過，尺寸較大的腫瘤，開刀效果較差，國外有些研究報告顯示，對於較大的腫瘤，先注射體抑素讓腫瘤縮小後再開刀，可提高成功率。林仁德指出，由於術後仍有40%～50%的患者，其生長激素及類胰島素生長因子數值居高不下，長期仍有造成身體併發症之不良影響，因此臨床上需以藥物持續控制。對於此類患者，目前建議每個月定期施打長效型體抑素，可有效抑制生長激素過度分泌，控制相關症狀，並需定期回診追蹤，以預防心血管等併發症的產生，以及不可逆的外觀變形。

長效型體抑素　緩解神經內分泌瘤症狀 優活健康網優活健康網 – 2015年3月26日 上午8:30長效型體抑素　緩解神經內分泌瘤症狀（優活健康網新聞部／綜合報導）你能想像一天跑廁所20至30次，卻找不到治療方法的痛苦嗎？就有一群患者因為罹患神經內分泌腫瘤，深受腸胃道潰瘍或慢性腹瀉等痛苦，造成生活品質低落；一名60歲男性病患經診斷後，發現罹患胰臟神經內分泌腫瘤，本來因為子女旅居巴西、無法就近照顧而無意再治療，但子女鼓勵她於台灣積極接受治療；在張義芳醫師的建議下，使用口服標靶藥物mTOR抑制劑治療長達2年之久，目前病情穩定控制，腫瘤沒有惡化，也幾乎沒有相關副作用產生，生活品質也得到了改善。咳嗽、氣喘、腹瀉腹痛等症狀　切勿輕忽！神經內分泌腫瘤（neuroendocrine　tumor，簡稱NET）為罕見的消化道腫瘤，好發部位為腸胃道及胰臟，其次則是肺部。馬偕醫院血液暨腫瘤科張義芳主任表示，神經內分泌腫瘤患者會依據病發部位產生不同的症狀，例如：咳嗽、氣喘、腹瀉、腹痛、盜汗及起紅疹等。大多數患者轉診到血液腫瘤科前，已經看過多科相關門診，且許多患者已出現轉移現象，無法藉由手術根治。能夠切除乾淨的神經內分泌腫瘤其第一線治療當然是以手術為主，但對於無法完全切除或是已經發生轉移的患者如肝臟或肺部轉移，病患的治療則需依靠藥物。張義芳主任表示，由於神經內分泌腫瘤為體內控制荷爾蒙分泌細胞發生病變所致，腫瘤會分泌過量的細胞激素，而產生不適的功能性症狀。張主任臨床經驗中，曾遇到一名老伯伯，因罹患神經內分泌腫瘤、且細胞激素分泌過多而引起長期腹瀉的症狀，深受常跑廁所的折磨，家人深感無力照顧下只好將他送至安寧中心；但在醫師的建議下，採用長效型體抑素治療，才緩解長期腹瀉症狀，明顯改善了病患的生活品質，讓病患更有尊嚴地回歸家庭生活。

長效型體抑素治療　緩解症狀並延緩腫瘤惡化 過去針對無法開刀及已轉移的神經內分泌腫瘤治療，多僅維持在控制症狀的階段。張義芳醫師表示，據臨床研究長效型體抑素除了可緩解功能性症狀外，亦可控制神經內分泌腫瘤的疾病進展，不論患者是否有功能性症狀的發生，此藥物皆可延緩腫瘤惡化時間。而針對原發於胰臟的神經內分泌腫瘤，使用長效型體抑素可以緩解及控制臨床功能性症狀；當疾病進一步惡化，從臨床試驗數據發現，合併搭配口服標靶藥物治療，可延緩腫瘤惡化達11個月之多。最後張義芳醫師表示，對於神經內分泌腫瘤患者，由於健保給付限制大，加上疾病帶給患者的身心之苦，除了需與醫師配合良好的治療方針，患者也要有與癌長存的鬥志，才能與疾病和平共處。若民眾欲取得更多衛教資訊及相關輔導協助，可至神經內分泌腫瘤資訊網查詢。

長效型體抑素類似物Octreotide(善得定長效緩釋注射劑)副作用低 有效緩解功能性症狀  神經內分泌腫瘤為體內控制荷爾蒙分泌細胞發生病變所致，依荷爾蒙分泌量之多寡，有些患者會產生不適的功能性症狀，通常症狀不易分辨，容易遭忽略或與其他疾病混淆，確診經常需要數年的時間，超過一半的患者已出現轉移現象，無法僅藉由手術根治，必須合併長效型體抑素類似物Octreotide之藥物治療；且NCCN治療指引建議以Octreotide作為功能性神經內分泌腫瘤的第一線治療。◎長效型體抑素類似物Octreotide ：•Octreotide為一種由8個胺基酸所組成的環狀胜肽，其藥理作用類似人類內生性荷爾蒙-somatostatin 。•能抑制生長激素及胃、腸、胰內分泌系統中胜肽的分泌。•對於肢端肥大症及胃、腸、胰內分泌腫瘤所造成的功能性症狀能有效的緩解。•皮下注射短效octreotide的半衰期可達到2小時，建議劑量為每天施打3次。•短效octreotide對內分泌引起症狀改善達88% 。•長效型效果和短效型一樣，每月只要一劑。•長效型體抑素類似物Octreotide可延長無惡化存活期。◎副作用控管：長效型體抑素類似物Octreotide在臨床上出現的副作用輕微且可忍受，少部分病患在腸胃道方面會出現新的膽道方面的異常，包括結石及膽道擴張等，其他胃腸道副作用為腹瀉、腹痛、脹氣、便秘、噁心及嘔吐，通常副作用在治療一周後症狀會改善。任何藥物治療都可能會有些許的副作用，當出現副作用時可尋求醫師的指示或經由飲食調整減輕不適感，如出現腹瀉症狀時，可吃些乾淨的流質食物（包括水、淡茶、蘋果汁或未添加其他固體食物的果凍），避免酸性飲料，如番茄汁、柑橘汁和碳酸飲料。對於原發於胰臟的神經內分泌腫瘤的患者，使用口服標靶藥物癌伏妥(Afinitor)+長效型體抑素類似物治療，口服標靶藥物癌伏妥(Afinitor)相較於其他標靶藥物來說，副作用輕微，臨床上出現的如口腔黏膜潰瘍、週邊水腫等，可透過事先投藥與輔助性療法就能獲得良好的控制，讓患者生活品質大幅提升。

體抑素類似物在肢端肥大症的治療應用 體內過多的生長激素作用在不同的器官所致的疾病症候群謂之肢端肥大症（若在骨𠕇癒合之前發生，則稱為巨人症）。其罹病率為50-70/每百萬人口, 發生率為3-4/每百萬人口。每年。換算為台灣2200萬人口，罹病率約為1100-1500病人，發生率約為每年新增70-90新病例。肢端肥大症絕大部份是由腦下垂體的生長激素分泌腺瘤所致。由於腫瘤生長緩慢，外觀症狀不論病人或醫生都不易察覺，生長激素分泌腺瘤在發現時多已是大於一公分的大腺瘤。其症狀包括局部腫瘤變大對蝶鞍及附近組織壓迫或侵犯以及其分泌過多生長激素所造成全身性的影響。治療肢端肥大症可以恢復病人外觀上的異常，減少腫瘤的大小。甚至在無症狀的肢端肥大症患者，降低生長激素也是必需的。因為流行病學研究指出，活動性肢端肥大症患者（未治療或治療後生長激素仍高者）比一般人在腦血管疾病，心血管疾病、呼吸道疾病以及惡性腫瘤方面多出了兩倍的死亡率。傳統上手術摘除腫瘤被視為治療生長激素分泌腺瘤的首選治療方式。手術可以治癒80-90%的微小腺瘤（小於一公分），但是卻無法治癒佔大多數病例的大腺瘤（根據報告，大腺瘤的治癒率小於50%）。另外一項治療的選擇是腦下垂體放射治療，但是要好幾年才看得出效果，並且有約一半的病人會有腦下垂體功能低下的副作用，需終生服用荷爾蒙補充製劑。第三個治療的選擇便是藥物治療。包括體抑素類似物以及多巴胺競爭劑。多巴胺競爭劑（例如bromocriptine）主要用在治療另一種腦下垂體腫瘤泌乳激素瘤，但用在治療肢端肥大症則有副作用太大以及效果不彰等缺點。體抑素類似物則是目前內科治療肢端肥大症最有效的方法。體抑素首先由Brazeau等人在美國發現。他們發現下視丘有一種荷爾蒙，可以抑制腦下垂體分泌生長激素，當時將之稱為體抑素。後來發現體抑素不只存在於下視丘，其他如胃腸道、胰臟等地方也存在。其功能不只是可以抑制生長激素分泌，也可以抑制胰島素、升糖激素、胃泌素等胃腸道荷爾蒙, 以及胰臟的外分泌功能等。這些重要的發現形成了以後體抑素類似物在臨床上許多用途的基礎（治療生長激素瘤、胰島素瘤、胃食道靜脈曲張出血、胃腸胰臟廔管等），但也因其多樣的作用，在治療生長激素瘤的劑量下，可能出現一些副作用。人類的體抑素為一種十四個胺基酸的胜太，在體內的半衰期只有三分鐘，應用在臨床上顯然不夠實際。於是有瑞士Sandoz藥廠研發出第一個體抑素類似物，叫做octreotide。Octreotide為有八個胺基酸的環狀結構。在原來體抑素與其接受體結合的必要的四個胺基酸之一的trp改成右旋Dtrp，另外在構造的羧端加以處理以減少酵素破壞。如此一來，octreotide 在體外的作用強度成為體抑素的七十倍，半衰期則大幅延長為九十分，大大地增加了在臨床上治療應用的可行性。因此在1988年美國食品藥物管理局通過octreotide可使用在生長激素瘤的病人。目前我們的作法是使用於開刀或者/以及放射治療後生長激素仍高的病人，但需事先申請通過後，才能使用。劑型為100symbol 109 \f "Symbol" \s 13mg/Amp（約550元），每天三次皮下注射一個月的花費約50000元，一年約600000元。一天三次皮下注射，雖嫌麻煩，但十多年來的臨床經驗顯示，Octreotide治療肢端肥大症確有療效：

40-65%的病人生長激素可以有效地抑制在正常範圍以下。有53%的病人可達到正常的IGF-I（第一型類胰島素生長因子）水平。大部份病人腦下垂體腫瘤可見到縮小（程度大都<50%）。臨床症狀的改善：頭痛、多汗、關節痛、疲倦等症狀可在54% ~ 78%的病人獲得改善。Octreotide的副作用 Octreotide皮下注射後，局部可能有紅腫疼痛現象，通常並不嚴重。另外在胃腸道方面，注射後數個小時可能有噁心，腹部絞痛、暫時性脂肪便等現象，10-14天後會逐漸改善，必要時可使用其他藥物改善症狀。血糖的變化 因為octreotide也抑制胰島素的分泌，所以會造成葡萄糖耐受性變差。有趣的是，原來因為肢端肥大症造成的續發性糖尿病，卻會隨著octreotide的治療而改善。膽囊結石 長期（一個月以上）octreotide的使用，膽固醇膽囊結石的發生率會增加，約在20-30%左右。通常是無症狀的膽結石。處理方式與其他原因引起的膽素結石是一樣的（內科藥物治療給予或外科膽囊切除）。一般建議在octreotide或其他體抑素類似物治療期間，每六個月追蹤一次膽囊超音波。罕見的副作用包括急性胰臟炎，非幽門螺旋桿菌引起的胃炎等。

長效體抑素抑制物 前面提過octreotide治療肢端肥大症需要病患每日自行皮下注射三次，雖然有效，但卻非常的不方便。有鑑於此，藥廠便致力於更長效劑型的研發。目前可以應用的有下列二種：Slow-release lanreotide（SR lanreotide）這是由法國Beaufour Ipsen International製造的。每十天至二星期肌肉注射一次。Octreotide-LAR 這是由原來製造octreotide的Sandoz藥廠改組後的Novartis藥廠研發出來的。美國食品藥物管理局已經在1998年12月核准其使用於肢端肥大症，每四星期肌肉注射一次。

結語：肢端肥大症絕大部份是因為腦下垂體腫瘤分泌過多的生長激素所致。治療（手術切除或放射治療）腫瘤以降低生長激素，不但可以延長病人壽命，也可以改善許多臨床症狀以及病人外觀。在手術未能徹底摘除腫瘤或是放射治療效果尚未完全發揮之時，生長激素濃度仍高的病人，可以使用體抑素類似物治療，有不錯的效果。

(牛樟芝) 易宏生技(蘇睿騏) 安卓幸(Antrocin) 雍有50種指標成分標準品 !

牛樟芝為基礎，易宏欲發展台灣原生系列農業生技 MoneyDJ新聞 2015-10-02 07:41:04 記者 蕭燕翔 報導 易宏生技(7421)於上月30日登錄興櫃，經營團隊指出，看好台灣雙原生種的牛樟芝發展，未來期許利用該公司在該領域整合技術與專利成分的優勢，將台灣牛樟芝發展成像韓國人蔘的地位，未來也將以牛樟芝為基礎，發展一系列台灣原生種的農業生技。易宏生技是在2010年由董事長蘇睿騏創立，目前實收資本額為1.81億元，發展的重要歷程包括2012年自農委會林試所技轉牛樟實生苗技術，同年8月與朝陽大學技術合作，12月與北京化工大學簽訂牛樟芝技術與生產合約；2013年1月完成第一代牛樟芝膠囊上市，2013年4月獲國發基金投資；2014年1月完成登錄創櫃板，5月完成中科第二培育廠建廠，用以量產牛樟椴木子實體與固態類子實體，12月完成安卓幸(Antrocin)合成，並與國內醫學機構展開抗癌動物的預實驗；2015年4月取得極樟芝、醇樟芝、解酒膠囊等四款牛樟芝膠囊產品的大陸衛生證。因蘇睿騏科技業的背景，現該公司的股東成份中，也不乏科技業知名人士，如F-TPK(3673)董事長江朝瑞、定穎(6251)電子創辦人等，據統計，目前股東來自科技業的持股比例近兩成。易宏副總張孟義表示，牛樟芝算是台灣的雙重特有，除牛樟芝為台灣特有種外，也寄生在台灣特有種的牛樟木上，因此台灣發展具備利基，不怕全球其他國家切入。  張孟義指出，國內發展牛樟芝的業者林立，價格差異極大，主要培育方法可以分為液態培育、固態培育與椴木培育，液態培育發酵僅需2週，但指標性成分含量低，價格也最低；固態培育則需耗時2個月，指標成分介於兩者之間；椴木培育雖得耗時8個月培育，但指標成分最高。他分析，相較於其他業者，易宏的優勢在於自種子、育苗到造林的一條龍垂直整合技術，且擁有近50種牛樟芝指標性成分標準品。且不同於液態與固態培育生成的菌絲體與類子實體，椴木培育可生成子實體。而在主管機關新法於2016年7月1日後，牛樟芝子實體的字樣使用須更名符其實、從嚴管理下，該公司已將產品送交檢測單位，完成添加子實體成分檢測，成國內首例；新法規上路後將有助於消費者分辨牛樟芝的實質應用部位，以示區別。他說，中國大陸食品藥品監督管理總局上月14日也最新通過，將台灣牛樟芝納入中草藥目錄清單，此也有助該公司將現有四款取得大陸衛生證的牛樟芝產品，擴大應用。董事長蘇睿騏則預期，登陸的效益於第四季後就會較明顯發酵。另外，易宏顧問也自牛樟芝發現具高度抗癌的成分安卓幸(Antrocin)，並成功研發出人工合成製程，且利用專利保護安卓幸衍生物，蘇睿騏說，未來會以該成分為基礎，開發系列抗癌新藥。蘇睿騏強調，易宏是以牛樟芝作為發展台灣原生種植物應用的起點，冀將台灣牛樟芝發展成像韓國人蔘的地位，並以此為基礎，發展一系列台灣原生種的農業生技。

柯文哲 定義的 盤尼西林反應 !!

特殊性關係 柯文哲舉例打盤尼西林休克 發稿時間：2015/10/01 12:16 最新更新：2015/10/01 14:30  （中央社記者黃麗芸台北1日電）日前備詢曾因聽到「特殊性關係」一怒搥桌，台北市長柯文哲今天看到馮光遠時表示，這跟打盤尼西林一樣啊，「第一次打沒事，第二次打就休克了」。  國民黨台北市議員徐弘庭日前在議會質詢波卡事件時曾說，柯文哲若繼續袒護時任悠遊卡公司董事長戴季全，「有一天馮光遠會說你和戴季全有『特殊性關係』」，柯一怒握拳搥桌，引發府會關係緊繃。  柯文哲及作家馮光遠上午一同出席「風格交易所百家店家」揭幕記者會，柯文哲致詞時表示，今天看到馮光遠在這裡，選其當台北觀察家應當是很有品牌才對，「很特別，很特別的關係，講到這個就講到那個」。 他說，一直沒機會跟大家講，人家問他聽第一次怎沒反應（徐弘庭曾二提特殊性關係），他說這跟打盤尼西林一樣啊，「第一次打沒事，第二次打就休克了」。  媒體會後聯訪詢問提盤尼西林之意？柯文哲說，盤尼西林通常第一次打沒反應，第二次打常就過敏休克，是回答外界問他為何之前在議會首次聽到「特殊性關係」沒反應，第二次聽到才有反應，「是替自己找個理由」。  柯文哲說，他是看到馮光遠才想到這件事。

玉山協會 王伯元連任前題(李紀珠續任副座)

李紀珠 將連任玉山科協副理事長 2015年10月01日 04:09 記者陳碧芬／台北報導 2015年台灣玉山科技協會年會昨（30）日晚間舉行，在台灣金控董事長李紀珠居中引介下，邀請到美國在台協會（AIT）處長梅健華進行抵台的首場公開演講。即將第4度擔任副理事長的李紀珠表示，玉山科技協會是非常重要的平台，她會持續以金融專業角色協助產業進行跨平台合作，拉近科技業在台灣的多元資金管道。台灣玉山科技協會昨天舉行年會，與會人士多達400人。  截至28日止的第八屆理監事通訊投票，當場公布理監事當選名單，包括現任理事長王伯元、副理事長李紀珠，鈺創董事長盧超群，工研院副院長劉軍廷，聯訊創投董事長苗豐強，聯發科董事長蔡明介等21位。玉山科協表示，10月8日將舉行第八屆首次理事會，將由各理監事互選出理事長。  據悉，該會現任理事長王伯元、也是創投業大老的怡和創投暨中磊電子董事長，原本有感於公務繁忙不再參與連任；惟在廣大會員熱情呼籲下，他應允連任的前題，是李紀珠續任副理事長。因此，下周理事會上，預估王伯元、李紀珠將共同連任。(工商時報)

科技部整合 腦科學/輔助科技/高齡營養食品!!!

提振經濟動能 科技部擴編明年預算 中央廣播電台／蕭照平-2015年09月30日 上午09:49   科技部長徐爵民今天(30日)表示，為了配合行政院各項經濟動能提升及產業轉型方案，明年度科技部擴編預算，希望在適切的經費下，持續創造豐碩的研發成果，並期以科技驅動國家整體競爭力、促進社會民生福址。  科技部長徐爵民30日赴立法院教育及文化委員會進行專案報告並備質詢，徐爵民在業務報告時指出，科技部配合行政院施政方針，運用科發基金塑造友善的研發與產業發展環境。  此外，為了配合提振經濟動能、產業轉型政策，徐爵民表示，政府擴編科技預算，希望藉此創造更豐碩的研發成果。徐爵民說：『(原音)推動加速行動寬頻服務及產業發展方案、生產力4.0發展方案、創意台灣智慧政府計畫、台灣矽谷科技基金計畫等，105年度科技預算擴增投入1,032.65億，較104年度約增加4.9%。』  而在規劃前瞻技術研發與產學鏈結部分，科技部更推動多項計畫與方案，其中為因應台灣高齡化社會問題，科技部整合「腦科學」、「輔助科技」、「高齡營養食品」等領域進行研究。徐爵民說：『(原音)期能以工程技術結合生醫臨床科技研究及成果，提升老年人口醫療及生活品質，促進科研產出應用於人類福祉之效益。』  除各項計畫外，徐爵民還說，科學工業園區已經成為國內高科技產業的成長引擎，去年3個園區總營收達新台幣2.3兆元，史上第4度突破2兆大關；而今年1月到8月的營業額估計，更大約有新台幣1兆4千多億元，因此科技部未來會持續支持高科技產業發展。