Results of a small clinical trial suggest that supplementing chemotherapy with high doses of vitamin D may benefit patients with metastatic colorectal cancer by delaying progression of the disease, say scientists from Harvard-affiliated Dana-Farber Cancer Institute.Prompted by the “very encouraging” results of the Sunshine clinical trial, the potential benefits of vitamin D supplementation in metastatic colorectal cancer will be evaluated in a larger clinical trial planned to open at several hundred sites across the U.S. later this year, said Kimmie Ng, director of clinical research in Dana-Farber’s Gastrointestinal Cancer Center, and corresponding author of the Sunshine study. “To our knowledge, this study is the first completed randomized clinical trial of vitamin D supplementation for treatment of advanced or metastatic colorectal cancer,” Ng said.In the high-dose group, patients had a median delay of 13 months before their disease worsened; in the low-dose group, the median delay was 11 months. In addition, patients in the high-dose vitamin D group were 36 percent less likely to have disease progression or death during the follow-up period of 22.9 months. The trial included too few patients to determine whether those who took high-dose vitamin D survived longer overall.“The results of our trial suggest an improved outcome for patients who received vitamin D supplementation, and we look forward to launching a larger trial to confirm these exciting and provocative findings,” said Charles Fuchs, formerly of Dana-Farber and now director of Yale Cancer Center, the senior author of the study.The initial findings were reported at the 2017 meeting of the American Society of Clinical Oncology. Those results, along with additional data, are now being published in the Journal of the American Medial Association.The Sunshine trial randomized 139 patients with previously untreated metastatic colorectal cancer. One group took pills containing 4,000 international units (IU) of vitamin D per day along with standard chemotherapy, while the other group took 400 units (about the dose found in a multivitamin) along with chemotherapy.Vitamin D, which is necessary for bone health, is made in the body through a chemical reaction dependent on sun exposure and is contained in some foods. In laboratory studies, vitamin D has demonstrated anti-cancer properties such as triggering programmed cell death, inhibiting cancer cell growth, and reducing metastatic potential. Prospective observational studies have linked higher blood levels of vitamin D with lower risk of colorectal cancer and improved survival of patients with the disease, but those studies could not prove that vitamin D was the cause.Against this backdrop, the randomized, prospective phase 2 Sunshine trial recruited patients at 11 academic and community centers across the U.S. to test whether vitamin D supplementation can improve outcomes in patients with metastatic colorectal cancer. All patients received standard chemotherapy. Patients in the high-dose vitamin D group initially took 8,000 IU a day for 14 days, then 4,000 IU a day thereafter. The low or standard-dose vitamin D group took 400 IU daily during all cycles. All patients were asked not to take any other vitamin D or calcium supplements during the trial period.The trial’s primary outcome measure was progression-free survival — the time until the disease began to worsen, or death — and it was longer in the high-dose group. Another measure that was calculated, the hazard ratio for disease progression or death, revealed 36 percent lower odds in the high-dose group.The researchers also sampled patients’ blood to measure changes in the levels of 25-hydroxyvitamin D [25(OH)D], which is a standard test to determine a person’s vitamin D status. This test showed that only 9 percent of the patients in the clinical trial had sufficient vitamin D at the beginning of treatment. Over the course of the study, patients receiving low doses of the supplement had no substantial change in their vitamin D levels, while those in the high-dose group soon reached the vitamin D-sufficient range and maintained it. Related Harnessing nature to beat cancer Wyss Institute researchers are inventing new ways to fight the deadly disease Seeing things in a different light System converts low-energy photons to high-energy, could be used in a host of applications Analysis of the results showed less benefit from high-dose vitamin D in patients who were obese, and those whose tumors contained a mutated KRAS gene, suggesting “that certain subsets of patients may need even higher doses of vitamin D for anti-tumor activity,” the researchers said. They cautioned, however, that high doses of vitamin D shouldn’t be taken except within the context of a clinical trial.The study and its findings are “extremely important,” Ng said, because “it identifies a cost-effective, safe, and easily accessible agent as a potential new treatment for metastatic colorectal cancer. This could therefore potentially have a large and wide-reaching impact globally, regardless of a patient’s socioeconomic status or a country’s resources.”The research was supported by National Cancer Institute grants P50CA127003, R01CA205406, and R01CA118553; a Gloria Spivak Faculty Advancement Award; a Friends of Dana-Farber Cancer Institute Award; the Project P Fund; Consano; Pharmavite LLC; and Genentech.Ng reports grants from National Cancer Institute, grants and non-financial support from Pharmavite, grants from Genentech, and grants from Consano during the conduct of the study; grants and non-financial support from Pharmavite, personal fees from Genentech, personal fees from Lilly, grants from Gilead Sciences, grants and personal fees from Tarrex Biopharma, personal fees from Bayer, personal fees from Seattle Genetics, grants from Celgene, and grants from Trovagene outside the submitted work.
Public Discourse 17 February 2015Another strange sign of our age appeared more recently, with the enormous popularity of Fifty Shades of Grey, which has sold an astonishing 100 million copies, and set a record in the UK as the fastest-selling paperback of all time. The story depicts a young female ingénue who is gradually initiated by a wealthy and powerful man into a BDSM sexual arrangement—Bondage, Discipline, Dominance, Submission, Sadism and Masochism— in which she acts as his “submissive.” The heavily marketed movie version of 50 Shades of Grey was released on Valentine’s Day, raking in $94 million over its opening weekend.Tom Wolfe’s observations suggest that the random impersonal sexual encounter is a defining feature of our day and age. Likewise, the enormous popularity of Fifty Shades suggests that interest in the world of BDSM may be another. What should we make of this? Is there any cause for concern here?Fifty Shades: A Model of AbuseMy purpose here is not to examine the literary merit of Fifty Shades of Grey (or the lack thereof). Instead, I’m going to examine the phenomenon of BDSM from the perspective of a psychiatrist.In 2013, social scientist Amy Bonomi of Michigan State University published an interesting study titled “‘Double crap!’ abuse and harmed identity in Fifty Shades of Grey.” In this study, the relationship depicted in the story was assessed for characteristics of “intimate partner violence,” using widely accepted standards from the CDC for emotional abuse and sexual violence.This study found that nearly every interaction between the male and female protagonists in the book, Christian and Anastasia, was emotionally abusive. Their relationship includes typical features of abusive relationships, such as stalking, intimidation, and isolation. In fact, the book’s pervasive sexual violence meets the CDC’s definition of sexual abuse—including Christian’s use of alcohol to overcome Ana’s reluctance to consent. The researchers also found that Ana exhibited classic signs of an abused woman, including the sense of a constant perceived threat, stressful coping styles, and an altered sense of identity.A second study published in 2014 by the same author looked at 650 women aged 18-24; it found that the women who had read the book were more likely than those who had not read the book to exhibit signs of eating disorders and have a verbally abusive partner. Women who read all three books in the Fifty Shades trilogy were found to be at increased risk of engaging in binge drinking and having multiple sex partners—known risks associated with being in an abusive relationship.There are limitations to this study: it did not distinguish whether women experienced the health behaviors before or after reading the books, so we cannot say whether the book contributed to these behavioral problems. It’s entirely possible that some women were more drawn to the book because they struggled with these behavioral issues already. But Bonomi argues that the findings are problematic either way. As she explains it:If women experienced adverse health behaviors such as disordered eating first, reading ‘Fifty Shades’ might reaffirm those experiences and potentially aggravate related trauma. Likewise, if they read ‘Fifty Shades’ before experiencing the health behaviors seen in our study, it’s possible the books influenced the onset of these behaviors.The Problem of ConsentThose who defend BDSM, like those who defend the campus hook-up scene, usually rest their case on one element and one element alone. That element is not love. That element is not fidelity. That element is not commitment. It’s not even pleasure.That element is consent.This one feature is seen as all-important and decisive. On this social contract model, as long as both partners consent, then everything is okay. As long as both partners consent, no one is harmed in the process. In Fifty Shades, although Ana is ambivalent and reluctant—it takes her a while to warm up to the BDSM arrangement—she eventually consents to the masochistic/submissive role. Well, then, no harm, no foul. Right?Wrong.First, people often consent to things that they are not really comfortable with; they do so for many different reasons and under many different social pressures. We see this clearly in Ana’s reluctance to sign Christian’s contract. Second, people often consent to things that turn out to be quite harmful to them. For consent to be authentic consent, it must be truly informed. To consent, people must understand the risks of what they are agreeing to do. This is a basic tenet of medical ethics, and it applies here as well.I recall one patient I treated, a young man who was one of the smartest people I’ve ever met. He was in a committed relationship with a similarly brilliant but troubled young woman. She wanted him to hit her during sex. He consented . . . sort of. That is, he agreed, and he did it, but he never really liked it. He was always reluctant. It troubled him, and eventually it got in the way of things. The relationship, as you might expect, eventually fell apart.http://www.thepublicdiscourse.com/2015/02/14470/?utm_source=The+Witherspoon+Institute&utm_campaign=a2e410a62d-RSS_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_15ce6af37b-a2e410a62d-84094405
The termination VFA, which is central to one of Washington’s most important alliances in Asia, was due to take effect in August and was Duterte’s biggest move yet towards delivering on longstanding threats to downgrade ties with the Philippines’ former colonial ruler.On Feb. 11, Duterte ordered the abrogation of the VFA after the US revoked the visa of former Philippine National Police chief and now senator, Ronald Dela Rosa, his close ally.Locsin said many countries in the region and the world find the Philippine government’s decision reassuring.“Let me assure you that this action alarms no countries in Asia and the rest of the world. On the contrary it greatly reassures everyone,” Locsin said.The US welcomed the Philippine government’s decision in a statement released after Locsin’s social media post.“Our long-standing alliance has benefited both countries, and we look forward to continued close security and defense cooperation with the Philippines,” a US Embassy statement said.Meanwhile, Defense secretary Delfin Lorenzana welcomed the development saying this could mean more US assistance at the time the country is facing the coronavirus disease 2019 pandemic.The VFA governs the treatment of US servicemen in military units and defense personnel who are in the Philippine territory for short periods for joint military exercises approved by both the Philippine and US governments.It entered into force on May 27, 1999 , eight years after the closure of US military bases in the Philippines in 1991. It was negotiated and signed during the time of President Fidel V. Ramos and ratified during President Joseph Estrada’s time.Over the years, the US military also assisted the Armed Forces of the Philippines in combating extremist groups by providing technical assistance and enemy surveillance to Filipino troops battling the militants. (With Reuters/PN) United States Marines arrive in an amphibious assault vehicle during the amphibious landing exercises of the US-Philippines war games promoting bilateral ties at a military camp in Zambales province, April 11, 2019. ELOISA LOPEZ/REUTERS/FILE ‘Superpower tensions,’ pandemic led Duterte to backtrack MANILA – President Rodrigo Duterte has suspended his decision to terminate a two-decade-old troop deployment agreement with the United States (US) due to “political and other developments in the region.” Foreign secretary Teodoro Locsin Jr. announced Tuesday that President Duterte reversed his decision to abrogate the Visiting Forces Agreement (VFA) and ordered the suspension of the agreement for six months.“We look forward to continuing our strong military partnership with the US even as we continue to reach out to our regional allies in building a common defense towards enduring stability and peace continuing economic progress and prosperity in our part of the world,” Locsin said.