Podcasts about irinotecan

Arndt Vogel (Toronto General Hospital) discusses the NALIRICC trial of nanoliposomal irinotecan added to fluorouracil plus leucovorin in patients with cholangiocarcinoma and gallbladder carcinoma previously treated with gemcitabine-based therapies.Read the full article:https://www.thelancet.com/journals/langas/article/PIIS2468-1253(24)00119-5?dgcid=buzzsprout_icw_podcast_generic_langasContinue this conversation on social!Follow us today at...https://twitter.com/thelancethttps://instagram.com/thelancetgrouphttps://facebook.com/thelancetmedicaljournalhttps://linkedIn.com/company/the-lancethttps://youtube.com/thelancettv

In part one of a two-part conversation, Drs. Patrick Loehrer and David Johnson sit down with Dr. Deborah Schrag to discuss her roles as a leader, researcher, oncologist and public health expert. The current Chair of the Department of Medicine at Memorial Sloan Kettering Cancer Center in New York, Dr. Schrag discusses the joy and passion she has found throughout her career, and more. If you liked this episode, please subscribe. Learn more at https://education.asco.org, or email us at education@asco.org.   TRANSCRIPT Dr. Pat Loehrer: I'm Pat Loehrer. I'm the Director of the Center of Global Oncology and Health Equity at Indiana University. Dr. David Johnson: Yes. And hello, I'm David Johnson. I'm at UT Southwestern in Dallas, Texas. Dr. Pat Loehrer: And welcome to another version of Oncology, Etc. Dr. David Johnson: Yeah, great guest today, before we get started with our guests, though, Pat, what are you reading these days? What can you recommend to me? Dr. Pat Loehrer: Well, I'm reading Jamie Raskin's book, which is about his son and about the insurrection. It's really a wonderful read so far, particularly I think about the family nature and how much he deeply respected his son who unfortunately committed suicide. Dr. David Johnson: Right before one of the impeachment trials as I recall, right? Dr. Pat Loehrer: It was right before the January 6 insurrection. Dr. David Johnson: Yeah, terrible situation. I have a book I've been meaning to recommend for a while. It's one that I've given to all the chief residents I've worked with over the last several years. And today's guests made me think about this book. It's entitled, Osler: Inspirations from a Great Physician. It's written by Charles Bryan, who's the former Chair of Medicine at the University of South Carolina in Columbia. Dr. Pat Loehrer: You trained with Osler, didn't you? Dr. David Johnson: I was a couple of years behind him. He was my senior resident. For anyone who's an Oslerphile, it's a great book to have. But even if you're not, it's got some wonderful lessons to be learned about how to interact with one's colleagues, and a lot of information about leadership, which is why it made me think of today's guest, Dr. Deborah Schrag who we're really excited to welcome to Oncology, Etc. Dr. Schrag is the Chairman of the Department of Medicine at Memorial Sloan Kettering Cancer Center in New York. She's a highly accomplished healthcare leader, clinician-researcher, and expert in public health and population science. Deborah received her medical degree from Columbia University and completed her residency in internal medicine at Brigham and Women's. She obtained her medical oncology training at Dana-Farber in Boston and also received an MPH degree from the Harvard School of Public Health. After a brief stint on the faculty at DFCI and Brigham and Women's, she joined the division of gastrointestinal Oncology at Memorial Sloan Kettering, where she was an associate member and Associate Professor of Public Health and Medicine. In 2007, I believe it was, she returned to Dana-Farber and Brigham, where she continued her work focused on improving the delivery, quality, and effectiveness of cancer care. While there, she served as chief of the Division of Population Sciences until this past year when she returned to Memorial to chair the Department of Medicine. I also think she's the first woman to hold this position, but we'll learn about that momentarily. Deb is internationally recognized as a pioneer for her work engaging patients in reporting outcomes as a way to improve care. She has led pragmatic trials using informatics strategies to optimize patient and clinician wellbeing, efficiency and quality, and equity of care. In short, she's a true superstar, leading the department, the major department, in one of the world's foremost Cancer Institutes. Deb, welcome to Oncology, Etc. Thank you so much for accepting our invitation. This is a relatively new oncology podcast, but already, we're known for our incisive, deeply penetrating questions. So, I have a question for you to start off. Do you have any carpentry skills? Dr. Deborah Schrag: Absolutely none whatsoever, Dave. None. Dr. David Johnson: I'm disappointed. It's my understanding that Schrag is German for cross or a slant and people who build cross-legged tables. So, I was hoping, my house was destroyed recently, and I'm looking for replacement furniture, and I was hoping you might be able to help me. Dr. Deborah Schrag: I apologize. But I'm not going to be able to help. The name, you're correct, though, David, is a German name. So, my family does hail from Germany and they made malt, which is the major ingredient in beer. I'm not sure where the name comes from. But they ran malt factories and shipped malt all over to all the beer, before there were craft beer distilleries, that's what they did. Dr. Pat Loehrer: That may come in handy by the end of this podcast, by the way. Dr. Deborah Schrag: Could be. Dr. David Johnson: Well, speaking of your family, tell us a little bit about your background and where you were raised, and your family members. Dr. Deborah Schrag: Sure! I'm glad you asked that because I really have been very influenced by where I grew up. And as I think about it, experiences that go back to first grade got me where I am today. So, I am from New York City. I grew up in Manhattan in the 1970s. And as you may know, that was a pretty rough time in the history of New York, what's often referred to as the 'bad old days', although it didn't feel that way to me. But I started out attending New York City public schools. And at that time in my neighborhood on the Upper West Side of Manhattan, my first-grade class had about 45 students, and one teacher, there were about five or six of us who spoke English, and everyone else was a recent Puerto Rican immigrant. I pretty much sat in the corner and read to myself. Now I didn't stay in the public school system for long, but I saw in first grade, how things weren't fair. And I saw and felt my own privilege, acutely. And even as a little kid, I had that sense. Eventually, my parents transferred me to private school later on. And there were kids in the neighborhood who didn't have the same privileges that I did. But living in New York, you walk around, you're confronted with disparities every day. We still see it today with homelessness on the streets. At that time, there was a lot of alcoholism and the use of drugs. And they were two blocks north that were safe to walk and two blocks east that were not safe to walk. So, this really stuck with me from a very early age. As a student in summer jobs, I worked lots of interesting jobs. I started at 14 scooping ice cream at Baskin Robbins, I worked at a famous Deli in New York called Zabar's, selling coffee. Lots of interesting jobs that I worked during holidays and vacation times. But one of my first jobs was working in an organization called the Floating Hospital, which was a big old ferry boat that circumnavigated Manhattan, and it provided a summer camp. And we would take 1800 people on a boat around Manhattan every day. And my job was to do lead testing. And I learned how to stick kids, test them for lead because there were incredible amounts of lead poisoning in New York City in the early 1980s. And then we would work on tracing the kids and these were toddlers, two-year-old, three years old. There were many families who were living in homeless shelters in New York City in the early 1980s. And that was really the beginning of my interest in public health and inequities. And really the marriage of medicine and public health. That had a deep and long-lasting impression on me and really stayed with me throughout my career. That early experience, I think it propelled me into medicine and to medical school and also to marry medicine and public health. Dr. Pat Loehrer: Tell me a little bit, Deb, about your parents. Dr. Deborah Schrag: Sure! My mother was born in the United States. She was a teacher who many years later after having three children went to law school and she became a litigator. And actually, her boss was Rudolph Giuliani. My father is a child of World War II. He was a child of German Jewish parents who had to flee the Nazis. Probably the most interesting story is that my paternal grandfather was an OB-GYN. So, I am a fifth-generation physician. My paternal grandfather was an OB-GYN at Charité, which is a very famous Hospital in Berlin. He was the head of OB-GYN there in the 1930s. But he had, I think he was half Jewish, and the Gestapo asked him to leave and he had to leave. He was an expert in version, which is essentially flipping babies and the setting of placenta previa. He then left for Lebanon, where he was in the French Resistance and had a thriving OB-GYN practice in Beirut, Lebanon, during World War II. And at night, there was a curfew, and he was part of the resistance and passed secrets around from the Russians to the French, so very dramatic. My father was born in this setting, and arrived as a new immigrant to the United States in the 1940s, where it was very hard to be a child whose parents had a German accent, given the prejudice against Germans at that time, but also went to New York City public schools, had a tremendous opportunity. It's really kind of the classic New York immigrant success story. You know, arrived in the United States with the shirts on their back and managed to work their way to a better life and achieve success and good education through public education for all their offspring. I will also say that my father had a public health stint. He worked in North Carolina as an alternative to going and serving in the Vietnam War, he was in the Public Health Service. And he worked in North Carolina in the textile mills and worked on a disease called byssinosis, which is also known as the brown lung. It's an occupational health disease that affects textile mill workers. As a child, I spent many dinners, hearing about byssinosis and brown lung, and black lung. I think at an early age I really came to understand how the world wasn't fair, and how it was instilled in me early on that it was important to work to try to make things better, particularly for people who didn't have privilege. And I think when you come from an immigrant family, and you realize how much privilege has been bestowed on you, that really leaves an indelible mark. I have to say, as Chair of Medicine at MSK, it is staggering to me the proportion of faculty here at MSK, but also at Dana-Farber, where I worked previously, we have lots and lots of immigrants who've been able to accomplish just amazing things through just motivation and drive and energy and creativity. And so, I'm a big believer in how much immigrants have powered this country. Dr. Pat Loehrer: Deborah, are your parents still alive? Dr. Deborah Schrag: My parents are still alive. They're both in their early 80s. And they both still live on the Upper West Side of Manhattan. So, I'm very privileged and fortunate to have living parents. Dr. Pat Loehrer: I can imagine the pride that they have for you. Dr. David Johnson: I just want to jump in and let our listeners know that Deb mentioned Charité in Berlin. That's the home of multiple Nobel laureates that all of us would know like Ernst Chain, who was one of the individuals involved in the development of penicillin, but Paul Ehrlich, Robert Koch, Hans Krebs, and for cancer doctors, Otto Warburg, among others. So, it truly is a world-renowned institution. Dr. Deborah Schrag: Well, my paternal grandfather was famous for this technique called version, which essentially involves putting your stethoscope next to the uterus, figuring out where the placenta was, and then essentially trying to flip the baby without disrupting the placenta or causing any harm, which required incredible skills with a stethoscope because you had to appreciate, I guess, the placental vessels. I'm not aware that this skill is still in existence, it was an important skill to have in the 1930s. When, if you did a C-section, there was a high probability of endometritis. So, you could save the baby, but you would often lose mom to endometritis. Or you could save mom, but you might not save the baby. So, at that time it was a big deal, but thankfully no longer. Dr. David Johnson: This is why we call it an Oncology, Etc. Our listeners didn't know that we're gonna get OB information in this particular podcast. Dr. Deborah Schrag: Or a digression on the history of medicine. I do find that, you know, I am inspired by the generations that came before me. I think it's also true that there are many physicians who are first-generation physicians in their families and some of us are privileged to have lots of healthcare professionals and sort of feel it as a calling. Dr. David Johnson: I think of you with many, many talents. But one of the things that I think stood out to me is, many years ago, you were in the van, talking about the financial cost of health care. I remember a very influential paper you wrote in the New England Journal, talking about the cost of treating GI cancer, colon cancer in particular. But where did your interest in that particular aspect of health care begin? What was the stimulus there? I mean, obviously you had a lot of stimulus from your family. What else? Dr. Deborah Schrag: That's really interesting. This is a little bit of a history of oncology. At that time, I was an assistant professor and assistant attending in the GI oncology service, seeing lots of patients with colorectal cancer. And we were working on a clinical trial of a drug called ImClone C225. And that was the name of the protocol. And we were putting patients in that clinical trial. And you know what? This drug was working. We were getting excited and the drug was moving ahead. We looked at the Phase 1 data and we launched Phase 2. We had meetings with the research protocol nurse and the research assistants, team meetings, and I would say there were about 50 people who were aware between the GI oncologists and the nurses and all the research assistants. You guys know that it takes a village and even though the villages were smaller then and it wasn't a particularly large trial, there are many, many people involved and everyone had the sense that this drug might be working. Just for context for our younger listeners, this is back in the early aughts, and basically, the drug that we had to treat colorectal cancer was 5-FU in many different formats and Irinotecan. And that was it. Some people thought mitomycin might work a little bit, but it was so horrible that it really barely worked. But that was what we had in our bag of tricks. So, the fact that we had this ImClone drug that eventually came to be known as Cetuximab, was remarkable. So, here's what happened. It turned out that this is the drug made by the company ImClone. And there were some shenanigans, some insider trading. And one of the people caught up in insider trading, in addition to some people involved with the company itself was none other than Martha Stewart, sort of the famous homemaker who still publishes magazines to this day. And you may know that she actually did some time in federal prison as a result of insider trading on this drug. I remember being a junior attending, and all the people involved in the trial and all the cancer professionals, we all knew this was working. But everyone respected the confidentiality of the situation, of the patients, and all the integrity that goes into academic medicine. And I remain inspired by the integrity of all the professionals, the doctors, the residents. These were not affluent people. I can tell you. we were not paying research assistants a whole hunk of money. They investigated every trade made by this company. There were absolutely no shenanigans or improprieties from the hard-working folks who helped bring this drug to market. So, as this was going on, we had many patients who were not eligible for the trial who were interested in getting the trial. So, of course, we followed as this drug got FDA approved and came to market. You could check me but I believe it was February 2004, it was FDA approved. It came out with a huge price tag. It was approximately $10,000 per month. I was mad because I was taking care of regular New Yorkers at that point. I had public school teachers, I had patients on Medicare and they couldn't afford the 20% copay. Because $10,000 a month for Cetuximab, if you have a 20% copay and you're New York City, public school cafeteria worker, is not yet eligible for Medicare with a typical plan that a New York City public school system employee would have, that was $2,000 a month. And that did not work for one of my patients who is essentially what we used to call a lunch lady. I was so mad that I decided to channel that anger into writing what I think is a perspective for the New England Journal called, “The Price Tag on Progress”. I wrote that piece. I know that many, many people and many of my esteemed colleagues have continued to work in that area and do research on the economics of drug pricing and there are many, many experts. I didn't stick with that. Not that it's not interesting, and not that it's not important. It's incredibly interesting and important, but I felt that the solution needed to happen in the legislature, state legislature, federal legislature. I think that this is about social policies, and we need to advocate for appropriate health insurance programs to make it possible for people to get coverage when they have catastrophic illnesses, and we need to think about the entire approach to drug pricing in this country. I still think that's important. I'm not convinced that what we need is more research on the topic. I think we need more policymaking and laws on the topic. I think we're still dealing with this. I'm sad to say that it's been nearly 20 years since I wrote that perspective. But I think it was motivated by frustration, not being able to get my patient what she needed, and many patients thereafter. And just the incongruity between some people benefiting from insider trading and all the good people who were doing the right thing. Dr. Pat Loehrer: I just want to throw in one thing if I can. Len Saltz, who's one of your partners, it was a piece of that trial that he presented at ASCO talking about ImClone C225. And ironically, it had a 22.5% response rate. And Len said, it's a bummer that ImClone didn't call it C995. Dr. Deborah Schrag: You have no idea how often we used to talk about that, joke about that in the clinic. I have another good story about that drug, which I think really illustrates something I believe and I think it's actually something that Osler said but it's also something I have to say I learned from both of you. And it has to do with listening to your patient. So, I had a patient named Matthew, who was a young man, 34 years old. He walked into my clinic with a diagnosis of diffuse metastatic colorectal cancer with multiple bilateral pulmonary metastases, which came to light when his tennis game was off. He was, at that time, an early employee of a newly started company called Google. And he was working on advertising algorithms, and Matt got the drug Cetuximab. And unfortunately, he was on it for quite some time. He was on it for about five or six months. But eventually, it was pretty clear that we were coming to the end of the road. And he and his wife planned a vacation. This was part of his end-of-life process planning. It was their fifth wedding anniversary in the Berkshires. We worked so hard to get Matt to the Berkshires to a beautiful inn, and on Saturday night, my pager goes off, and Matt cannot sit up. He's weak. And he'd been complaining of terrible fatigue for weeks, to me, and I really hadn't quite figured out why Matt was so fatigued. I mean, I just didn't understand it. And we get into this inn and I get a call from the Berkshire Medical Center, a small community hospital, 'Dr. Schrag, your patient is here. He's so weak and he can't sit up.' 'What's going on?' The ER doctor says, 'Well, he has a Chvostek sign', which is a sign of severe hypocalcemia. 'So, call me back with the calcium.' The calcium is low. Well, I think those of your listeners who are closer to medical school know that when the calcium is low, you have to check the mag. And Matt's magnesium was 0.2. And he got some magnesium in the Berkshire Medical Center. And all of a sudden, he felt great. He was able to go on and enjoy the second half of his fifth anniversary weekend at the Berkshire Inn and he came back. And I felt terrible because he'd been complaining to me of fatigue for six weeks and I hadn't checked his magnesium. I was like, 50 bilateral pulmonary metastases on chemotherapy. That's a fatigue explanation. Suffice it to say that we went on to start checking magnesium on everyone getting Cetuximab. Now mind you, the drug is FDA approved and FDA labeled at this point. So, we started checking magnesium, and we find that it was low. I start getting on the phone and calling my mentors. I called Dr. Bob Mayer, who was the head of my fellowship director and was like a revered mentor to me. 'Hey, Bob, does anyone up there in Boston have low magnesium from Cetuximab?' 'We don't check magnesium.' I said, 'But can you check?' I started calling around and that's a great example of the community of oncology. We are a community. I just started working the phones and calling friends and saying 'You guys checking magnesium for any of these folks on Cetuximab?' Suffice it to say, we figured out that their EGFR receptors in the ascending loop of Henle - so, again, back to biology and pathophysiology - the drug Cetuximab was blocking reabsorption of magnesium in the kidney, and it was Cetuximab that caused a terrible magnesium wasting. Oral magnesium did not work. You had to give it intravenously, repeatedly. And we helped eliminate fatigue for a bunch of patients. About six months later, I showed up at ASCO with these little cardboard slides and a little poster back in the corner and put up our little case series, very little. But I'm proud to say that we changed the label of Cetuximab and it's now on the label that it causes hypomagnesemia. It might be one of my more cited papers, paradoxically. But I think it's a principle that really has stuck with me, and I've tried to impart it to all the students and residents and fellows, 'Listen to your patients because - I think it comes from Osler- they're telling you something. We have to pay attention.' Again, I have never forgotten that. But really listening and trying to figure out how we can use our understanding of pathophysiology and what our patients tell us to ask questions and not just accept dogma and try to figure out what we can do. And you know, I couldn't have figured that out on my own. I happened to find a really smart nephrologist who happened to be able to sort of go to animal models and knew the right studies and the right people to talk to. Dr. David Johnson: It's one of the reasons why we are a multidisciplinary specialty. And we use the expertise of our colleagues. I think that's such a wonderful example of listening to one's patient and it really profoundly impacted our understanding of how that drug works and renal physiology, actually. That wraps up part one of our interview with Dr. Deborah Schrag, Chair of Medicine at Memorial Sloan Kettering Cancer Center. We hope you've enjoyed learning about her background and her early career. In part two of our conversation, Dr. Schrag will discuss her programmatic goals at Memorial Sloan Kettering, the importance of mentorship and leadership, and what it means to have joy in the profession of medicine, and, frankly, much more. So, please be sure to join us. As always, we want to thank you for tuning in to Oncology, Etc. an ASCO educational podcast, where we will talk about just about anything and everything. So, if you have an idea for our topic or a guest, please email us at education@asco.org. Unknown Speaker: Thank you for listening to the ASCO Education Podcast. To stay up to date with the latest episodes, please click subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive education center at education.asco.org.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.

Host Dr. John Sweetenham, associate director for Clinical Affairs at UT Southwestern Harold C. Simmons Comprehensive Center, and Dr. Robert Carlson, CEO of the National Comprehensive Cancer Network (NCCN), discuss novel therapies and compelling health equity research featured at the 2022 NCCN Annual Conference.   Transcript:   Dr. John Sweetenham: Hello, I'm John Sweetenham, the associate director for Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and host of the ASCO Daily News podcast.   Today, I'll be speaking with Dr. Robert Carlson, the chief executive officer of the National Comprehensive Cancer Network or NCCN. Dr. Carlson will be telling us about key advances in cancer care that were featured at the 2022 NCCN Annual Conference.   Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcasts.   Bob, I'm really pleased to have you on the podcast today, and personally very excited to serve in my new role as chair of the NCCN Board of Directors.   Dr. Robert Carlson: John, it's a pleasure to be with you this morning and all of us at NCCN look forward to working with you as chair of the NCCN Board of Directors.   Dr. John Sweetenham: Thank you! Bob, there was such a wide breadth of topics that were covered at the NCCN Annual Conference this year. Could you tell us about some of the key abstracts that you think will advance care for patients?   Dr. Robert Carlson: I'd be happy to! We had over 1,000 participants from 40 countries at this year's Annual Meeting. And there were a number of high-quality abstracts reporting on a spectrum of studies, including NCCN young investigators and a number of other investigators.   Three abstracts that I would like to single out include an abstract entitled, “Real-World Data and Independent Predictors of Clinical Outcomes with CDK Inhibitors in Metastatic Estrogen receptor-positive Breast Cancer Patients” which was presented by Priyanka Reddy and colleagues from Case Western Reserve. They assessed how the real-world experience with the CDK 4/6 inhibitors in hormone receptor-positive metastatic breast cancer compared with a clinical trial experience. They retrospectively identified 269 patients with hormone receptor-positive metastatic breast cancer in the first-line setting and assessed progression-free survival and overall survival in the cohort overall, and also in the subset with bone-only metastatic disease in those who had liver involvement.   In the overall cohort, the results demonstrated progression-free survival of 21 and a half months and overall survival of 57.6 months. In those with the bone-only disease, at 5 years, 84% of patients were alive compared with 42% in those with bone plus other visceral sites of disease.   They performed multivariate cox regression, and bone-only disease was an independent predictor of a favorable outcome with a hazard rate of 0.48 for progression-free survival, and 0.38 for overall survival, both highly statistically significant.   In those patients with liver disease, multivariable regression predicted an unfavorable outcome with a hazard ratio of 2.53 for progression-free survival and 2.24 for overall survival. So, the study found that the real-world experience with the CDK 4/6 inhibitors is very similar to that in clinical trials. And that bone-only disease continues to be a positive predictor of outcome and liver disease an unfavorable predictor of outcome.   Another important abstract was entitled, “Reuterin in the Healthy Gut Microbiome Suppresses Colorectal Cancer Growth through Altered Redox Balance,” and was presented by Joshua Goyert and colleagues from the University of Michigan.   This abstract reported on a series of findings related to alterations in the intestinal microbiome, especially related to reuterin, the metabolite from the lactobacillus reuteri.   The investigators found that the fecal metabolites from healthy subjects and wild-type mice suppress colorectal cancer, while metabolites from patients or mice with colorectal cancer do not.   Reuterin was found to be the most potent metabolite in suppressing colorectal cancer. And further study found that Reuterin was effective in inhibiting proliferation and inducing cell death of colorectal cancer, but also in cell lines of lymphoma, ovarian cancer, melanoma, and pancreatic cancer. Normal cells were not found to be at all affected. While early, this all suggests a novel strategy for treatment for translational investigation.   The final abstract to be highlighted was actually funded by the NCCN Oncology Research Program and is entitled “Phase 2 Trial Trifluridine/Tipiracil in Combination with Irinotecan in Advanced Biliary Cancers” and was presented by Sri Tella and colleagues from the Mayo Clinic Comprehensive Cancer Center.   Historically, biliary cancers have had very few and limited treatment options. This current study was an open-label phase two clinical trial in patients with biliary cancer and at least one prior systemic therapy to assess the activity of combination trifluridine/tipiracil plus Irinotecan. The subjects were treated with a regimen of trifluridine/tipiracil 25 milligrams per meter squared, orally, on days 1 through 5 on 14-day cycles, and Irinotecan, 180 milligrams per meter squared intravenously on day one of the 14-day cycles. The primary endpoint for success was 16-week progression-free survival. They enrolled 28 patients 27 of whom were available. And they found a 16-week progression-free survival of 37%, which exceeded their target rate of response of 30% or greater.   Overall survival was just over 1 year. While tolerated reasonably well, those reductions were common, and the investigators concluded that further evaluation in a randomized trial was needed.   Dr. John Sweetenham: Thanks, Bob. All very interesting abstracts. I think that makes important contributions. And in the spirit of interesting discussions at the NCCN, I must say that I personally felt that there were some very interesting and excellent sessions around health equity at the conference, including the plenary sessions.   I wonder if you could give us some key takeaways from those sessions looking at health equity, and also the one that specifically looked at access to cancer care, and equity in the context of access.   Dr. Robert Carlson: So, there were a number of sessions at the NCCN Annual Conference that related directly or indirectly to issues of access and equity of cancer care. I'd like to focus specifically on a plenary session that was devoted to equity in cancer care.   We all know that equities in cancer care are pervasive, and we can't just wish or decree away these disparities. We need to be willing to evaluate how each of us can change our own practice and how we can be an active part of larger systems change. And that is what this plenary session was all about—actively eliminating existing disparities in cancer care.   The session was moderated by Dr. Carmen E. Guerra of the University of Pennsylvania. It started with Thomas Farrington of the Prostate Health Education Network discussing the importance of cancer early detection and screening strategies that are designed to account for the differences in incidence and age distribution of cancers in different racial and ethnic groups.   Mr. Farrington used prostate cancer as an example of where Blacks have an especially high incidence, younger age distribution, and more aggressive prostate cancer than do other racial groups.   Liz Margolies of the National LGBT Cancer Network followed and stated that cancer doesn't discriminate, but the health care system certainly does. She talked about making welcoming spaces for sexual and gender minorities in cancer care settings, of truly learning and understanding the perspectives and needs of the LGBT communities, and gaining their trust. She concluded by saying that being well-intentioned is not enough—hard work is necessary.   Shonta Chambers of the Patient Advocate foundation described the importance of social determinants of health that included socioeconomic factors, physical environment, health behaviors, and health care access and quality. She emphasized the central importance of patient navigation in assuring appropriate access. She described using data and the social vulnerability index to target resources where they are needed the most.   Dr. Maria Garcia-Jimenez from UCLA outlined efforts to improve appropriate racial and ethnic representation across clinical trials, specifically by breaking down barriers to patient participation. Dr. Garcia-Jimenez described how these barriers exist at the health system level, with the provider, at the community level, which typically is through lack of trust, and at the patient level, through lack of trust, language, cultural differences, and lack of awareness.   Alyssa Schatz from the NCCN discussed the Elevating Cancer Equity initiative, which is a collaboration of NCCN, the American Cancer Society Cancer Action Network, and the National Minority Quality Forum, involving a number of additional representatives with expertise in disparities in cancer care. This initiative has developed a health equity report card, which includes 17 measures across 4 different domains, and that has been piloted currently at 5 NCCN member institutions to identify areas of racial access and equity needing improvement. The initiative also developed a series of policy priorities, primarily at the federal level that aimed at minimizing disparities.   The summary of this session is that talking about disparities is inadequate. It is crucial that we take positive and focused action to address existing disparities so that we can improve and facilitate equitable care for all patients. And that equity is everyone's responsibility.   Dr. John Sweetenham: That's great. Thanks, Bob. Yeah, there were 2 statements from that session, which really sort of struck home with me. I think, to your final point there, I know that one of the comments that were made was, 'It is great that there has been so much research in recent years, and so much emphasis in the literature on cancer care disparities. But doing research that demonstrates disparities doesn't actually help the patient. It's what we do about that, which is important. And it's sort of a statement of the obvious, but it's very impactful to me to think about that it's become an area of really quite extensive research, but we actually need some actionable conclusions from those research and to work really hard on that.   The other thing that was said that really struck home with me was the comment that “Cancer is a disease of the family.”' And certainly, the person who said that wasn't talking in the inherited sense, but really more of the impacts that cancer has on the family and the caregivers as a whole.   I thought they were both really impactful statements from what was a really excellent session. Bob, I really appreciate you sharing your insights with us today. Are there any other important messages you'd like to get across before we wrap up?   Dr. Robert Carlson: Well, the Annual Conference of the NCCN serves as a forum to discuss important and rapidly evolving NCCN clinical practice guidelines, to discuss best practices in administering cancer care, and to share the results of a wide range of research activities that relate to improving cancer care. We at NCCN invite the oncology community to next year's NCCN Annual Conference and review the endured materials that will be available sometime this June, from the conference that will be posted on the NCCN website.   Dr. John Sweetenham: Great, thank you! Thanks once again for spending time with us on the podcast today, and for the many contributions that NCCN has made, both nationally and globally, and indeed continues to make to advance quality, effective, equitable, and accessible care for all patients with cancer.   Dr. Robert Carlson: And thank you, John, we look forward to working with you as the chair of the NCCN Board of Directors to further extend all these efforts.   Dr. John Sweetenham: Thanks! Thanks also to our listeners for your time today. If you are enjoying the content on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness   Dr. Robert Carlson: Employment (immediate family member): Flatiron Health Patents, Royalties, Other Intellectual Property: Patents relating to inventions as an employee of NCCN Other Relationship: National Comprehensive Cancer Network   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product or service organization activity or therapy should not be construed as an ASCO endorsement.    

Internist-oncoloog prof. dr. ir. Koos van der Hoeven spreekt met drs. Emma Hulshof, ziekenhuisapotheker in het Catharina Ziekenhuis in Eindhoven, en prof. dr. Hans Gelderblom, internist-oncoloog in het Leids Universitair Medisch Centrum, over het voorkomen van ernstige bijwerkingen door irinotecan. Aan bod komen onder andere de studieresultaten die onlangs in The European Journal of Cancer zijn gepubliceerd, aanpassen van richtlijn en hoe UGT1A1 getypeerd kan worden.

ONS member Rae Norrod, MS, RN, CNS, AOCN®, oncology service line manager at Kettering Health Network in Ohio and member of the West Central Ohio ONS Chapter, joins Stephanie Jardine, BSN, RN, oncology clinical specialist at ONS, to discuss how oncology nurses can safely administer irinotecan chemotherapy and manage its associated side effects and adverse events. This episode is part of an ongoing series about outpatient oncology drug infusion. The others are linked in the episode notes. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at myoutcomes.ons.org by August 13, 2023. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of NCPD by the American Nurses Credentialing Center's Commission on Accreditation. Episode Notes Check out these resources from today's episode: Complete this evaluation for free NCPD. Previous Oncology Nursing Podcast episodes on outpatient oncology drug infusion ONS Voice article: The Case of the Pancreatic Phenomenon Oncology Nursing Forum article: Allelic Expression of Phase II Metabolizing Enzymes and Relationship to Irinotecan Toxicity ONS book: Clinical Guide to Antineoplastic Therapy: A Chemotherapy Handbook (Fourth Edition) ONS Communities thread on administering premeds to prevent diarrhea ONS learning library on safe handling of hazardous drugs ONS symptom management interventions for chemotherapy-induced diarrhea and mucositis ONS position statement: Education of the Registered Nurse Who Administers and Cares for the Individual Receiving Antineoplastic Therapies Irinotecan package insert Liposomal irinotecan package insert National Cancer Institute information on irinotecan To discuss the information in this episode with other oncology nurses, visit the ONS Communities.  To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org.

Featuring an interview with Dr Jaffer Ajani, including the following topics: Evolving Therapeutic Landscape of Upper Gastrointestinal Tumors (0:00) Case: A Man in His Late 50s with PD-L1-Positive, HER2-Negative, Microsatellite-Stable Metastatic Adenocarcinoma of the Gastroesophageal Junction (29:01) Case: A Man in His Mid-40s with HER2-Positive, Metastatic Gastroesophageal Cancer (30:35) Clinical Data on TAS-102 in Gastric Cancer (33:24) Ramucirumab with Irinotecan as Second-line Therapy for Patients with Advanced Gastric Cancer — Phase III RAINBOW-Asia Study (37:24) CME information and select publications

Anti-aging compound improves muscle glucose metabolism in people Washington University School of Medicine in St. Louis, April 26, 2021   A natural compound previously demonstrated to counteract aspects of aging and improve metabolic health in mice has clinically relevant effects in people, according to new research at Washington University School of Medicine in St. Louis. A small clinical trial of postmenopausal women with prediabetes shows that the compound NMN (nicotinamide mononucleotide) improved the ability of insulin to increase glucose uptake in skeletal muscle, which often is abnormal in people with obesity, prediabetes or Type 2 diabetes. NMN also improved expression of genes that are involved in muscle structure and remodeling. However, the treatment did not lower blood glucose or blood pressure, improve blood lipid profile, increase insulin sensitivity in the liver, reduce fat in the liver or decrease circulating markers of inflammation as seen in mice. The study, published online April 22 in the journal Science, is the first randomized clinical trial to look at the metabolic effects of NMN administration in people. Among the women in the study, 13 received 250 mg of NMN orally every day for 10 weeks, and 12 were given an inactive placebo every day over the same period. "Although our study shows a beneficial effect of NMN in skeletal muscle, it is premature to make any clinical recommendations based on the results from our study," said senior investigator Samuel Klein, MD, the William H. Danforth Professor of Medicine and Nutritional Science and director of the Center for Human Nutrition. "Normally, when a treatment improves insulin sensitivity in skeletal muscle, as is observed with weight loss or some diabetes medications, there also are related improvements in other markers of metabolic health, which we did not detect in our study participants." The remarkable beneficial effects of NMN in rodents have led several companies in Japan, China and in the U.S. to market the compound as a dietary supplement or a neutraceutical. The U.S. Food and Drug Administration is not authorized to review dietary supplement products for safety and effectiveness before they are marketed, and many people in the U.S. and around the world now take NMN despite the lack of evidence to show clinical benefits in people. The researchers studied 25 postmenopausal women who had prediabetes, meaning they had higher than normal blood sugar levels, but the levels were not high enough to be diagnosed as having diabetes. Women were enrolled in this trial because mouse studies showed NMN had the greatest effects in female mice. NMN is involved in producing an important compound in all cells, called nicotinamide adenine dinucleotide (NAD). NAD plays a vital role in keeping animals healthy. Levels of NAD decline with age in a broad range of animals, including humans, and the compound has been shown to contribute to a variety of aging-associated problems, including insulin resistance in studies conducted in mice. Supplementing animals with NMN slows and ameliorates age-related decline in the function of many tissues in the body.  Co-investigator Shin-ichiro Imai, MD, PhD, a professor of developmental biology and of medicine who has been studying NMN for almost two decades and first reported on its benefits in mice said, "This is one step toward the development of an anti-aging intervention, though more research is needed to fully understand the cellular mechanisms responsible for the effects observed in skeletal muscle in people." Insulin enhances glucose uptake and storage in muscle, so people who are resistant to insulin are at increased risk for developing Type 2 diabetes. But the researchers caution that more studies are needed to determine whether NMN has beneficial effects in the prevention or management of prediabetes or diabetes in people. Klein and Imai are continuing to evaluate NMN in another trial involving men as well as women.     N-acetylcysteine for depression in adolescents and young adults at risk for bipolar disorder University of Cincinnati, April 23, 2021 According to news reporting originating from Cincinnati, Ohio, by NewsRx correspondents, research stated, “To investigate the mechanism of action of N-acetylcysteine (NAC) in depressive symptoms in young individuals at familial risk for bipolar disorder. We conducted an 8-week open label clinical trial of NAC 2400 mg/days in 15-24 years old depressed offspring of a bipolar I disorder parent, with baseline and endpoint proton magnetic resonance spectroscopy acquired within the left ventrolateral prefrontal cortex (VLPFC).” Our news editors obtained a quote from the research from the University of Cincinnati, “Nine participants were enrolled and finished the study. NAC significantly improved depressive and anxiety symptom scores, and clinical global impression (all p< .001). There was a non-significant reduction in glutamate levels in the left VLPFC. Reduction in depressive symptom scores was positively associated with reduction in glutamate levels in the left VLPFC (p = .007).” According to the news editors, the research concluded: “This pilot study suggests that NAC might be efficacious for depressive symptoms in at-risk youth, and that its mechanism of action involves the modulation of glutamate in the left VLPFC.” This research has been peer-reviewed.     Soda consumption linked to accelerated aging and increased mortality risk University of California at San Francisco, April 26, 2021 A recent study by researcher from the University of California, San Francisco says that drinking soda can increase the risk of all-cause mortality and accelerate aging. The findings build on mounting evidence of the adverse effects drinking soda and other sugary beverages have on the body, which include obesity, Type 2 diabetes, heart disease, kidney disease, non-alcoholic fatty liver disease, dental caries and gout. The team collated data from the National Health and Examination Surveys, an annual program for assessing the health and nutrition of American adults and children. They gathered data from over 5,300 participants between 1999 and 2002, all of whom had no history of diabetes or cardiovascular disease.  In particular, they looked at stored DNA data from the participants – measuring telomere length and comparing it with their consumption of sugar-sweetened soda. The researchers found that those who regularly drank sugar-sweetened soda had shorter telomeres than those who didn’t. Research has shown that telomeres have been previously associated with lifespan. Having shorter telomere length, for instance, has been linked to cardiovascular disease, diabetes and even certain types of cancer. The team reported in their study that consuming even just eight ounces of soda every day can accelerate aging by nearly two years. Meanwhile, 20 ounces of soda can accelerate aging by up to 4.6 years when consumed daily. In fact, drinking sugar-sweetened soda can reduce telomere length at a rate similar to smoking. The UCSF study is also the first to link regular consumption of sugar-sweetened soda to telomere shortening. According to study co-author Elissa Epel, drinking sugar-sweetened soda adds strain to the body by metabolizing these sugars and accelerates cellular aging in tissues. “This finding held regardless of age, race, income and education level. Telomere shortening starts long before disease onset,” Epel added. ” Although we only studied adults here, it is possible that soda consumption is associated with telomere shortening in children, as well.” Sugary sodas linked to rising all-cause deaths In another study, European experts revealed that drinking sugary sodas and other sweetened drinks increases the risk of all-cause deaths. The researchers collected data from more than 450,000 individuals enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a large-scale cohort study for biochemical and genetic markers for cancer and other chronic diseases. A follow-up revealed that more than 40,000 participants from the original study had already died. Using their data, the team found a strong link between regular soda consumption and all-cause mortality. Those who regularly drank more than two glasses of sugary drinks increased their risk of dying from circulatory diseases, while those who drank at least one glass of sugary drinks increased their risk of dying from digestive diseases and Parkinson’s disease. “Our results … provide additional support for the possible adverse health effects of sugar-sweetened soft drinks and to replace them with other healthier beverages, preferably water,” explained co-author Neil Murphy. “For artificially-sweetened soft drinks, we now need a better understanding of the mechanisms that may underlie this association and research such as ours will hopefully stimulate these efforts.” The findings appeared in JAMA Internal Medicine.     Curcumin concoction could combat colitis: Study Baylor University, April 25, 2021 A formula that blends curcumin and turmeric oils can prove effective against the activity and inflammatory burden of colitis, a study has determined. Published in Nature Scientific Reports, the study identifies the efficacy of a specific curcumin preparation containing essential turmeric oils (ETO-curcumin) in reducing colitis symptoms. These turmeric oils, aromatic-tumerones (ar-tumerones), alpha-turmerones, beta-turmerones, alpha-santalene and aromatic curcumene, appear to be responsible for an anti-inflammatory and anti-oxidant action, the study suggests. The combination also appeared to exert higher bioactivity than stand-alone curcumin – a feature that could prove valuable in using turmeric for other intestinal conditions. “The therapeutic benefits of turmeric can be attained at its best by combining curcumin with turmerone, an active compound derived from essential oil of turmeric,” said P.J. Kunjachan, chairman and managing director for Arjuna Natural Extracts “This new finding provides our customers an added value for promoting their BCM-95-based formulations in an increasingly crowded curcumin market,” added Dr Benny Antony, joint managing director for Arjuna. BCM-95 often combines curcumin with other turmeric compounds as its poor bioavailability has been cited as a barrier to its use in other disorders. Obstacles are not limited to curcumin's chemical properties. Despite the 17 claims for its anti-inflammatory and digestive health properties, there are currently no approved health claims for curcumin in the EU. These claims are featured on the 2000+ list of on-hold botanical claims yet to be processed by the European Food Safety Authority (EFSA). As well as Arjuna, other manufacturers with an interest in curcumin include herbal manufacturers Sabinsa and Italian botanicals firm Indena. Led by Dr Shusuke Toden, research associate from Baylor University in the US, the trial compared ETO-curcumin preparations  against standard curcumin at three specific doses (0, 5, 25 or 50 milligrams per kilogram (mg/kg)). These doses were administered to an animal model with induced colitis for seven days. The research team found that ETO-curcumin improved disease activity index (DAI) dose-dependently, while the anti-inflammatory efficacy of standard curcumin remained constant. “This suggests that ETO-curcumin may provide superior anti-inflammatory efficacy compared to standard curcumin,” the study explained. “ETO-curcumin associated anti-inflammatory effects were particularly pronounced at higher doses.” Further findings revealed that anti-inflammatory proteins produced included IL-10 and IL-11 as well as FOXP3, which increased in number in the colon by ETO-curcumin.   Study examines association between lifestyle patterns and BMI in early childhood Results support obesity prevention efforts early in life Deakin University (Australia), April 26, 2021   A new Australian study reveals that changes in lifestyle patterns were longitudinally associated with concurrent changes in body mass index (BMI) z scores, and maternal pre-pregnancy BMI, maternal dietary patterns and television viewing time are significant determinants, according to a paper published online in Obesity, The Obesity Society's (TOS) flagship journal. This is the first study that used multi-trajectory modeling to examine the longitudinal relationship between concurrent changes in lifestyle patterns and BMI z scores in early childhood.  "The findings will inform early childhood obesity prevention intervention and policy, and will be of great interest to pediatricians, researchers, policymakers and the general public," said Miaobing Zheng of the Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, in Geelong, Australia. Zheng is the corresponding author of the study.  Experts explain that longitudinal studies investigating the association between lifestyle patterns and obesity in children are scarce. An association between a healthy lifestyle pattern and lower obesity risk has, however, been previously reported in a few cross-sectional studies. In the present study, the co-occurrence of stable healthy lifestyle patterns along with a concurrent normal BMI z score trajectory of one unit from 18 to 60 months in about half of the children provides new longitudinal evidence supporting that children with healthy lifestyles were more likely to concurrently have normal BMI z score development.  Data of 439 children were used from the Melbourne Feeding Activity and Nutrition Trial (InFANT) program. This longitudinal cohort of children commenced in 2008 as a 15-month parent-focused cluster randomized controlled trial aiming to reduce obesity risk behaviors in children until 18 months. Additional follow-ups without interventions occurred for children aged 42 and 60 months. Multi-trajectory modeling identified groups of children following similar lifestyle patterns and BMI z score trajectories and multi-nomial logistic regression assessed the determinants of the trajectory groups.  Three trajectory groups of child lifestyle patterns and BMI z scores were identified and distinguished, showing a mixture of healthy and unhealthy lifestyle behaviors and BMI zscores. Compared to Groups 1 "Unhealthy lifestyle pattern, Low BMI z" and 3 "Unhealthy lifestyle pattern, High BMI z", Group 2 "Healthy lifestyle pattern, Mid BMI z" revealed the most distinctive trajectories across lifestyle patterns and BMI z scores. Group 2 comprised nearly 53 percent of children and followed a stable and low trajectory for an unhealthy lifestyle pattern characterized by energy-dense and nutrient poor discretionary food consumption and television viewing time and a high and rising trajectory for a healthy lifestyle pattern of fruit and vegetable intakes and time outdoors, along with a mean BMI z score of +1 unit over time. Groups 1 and 3 shared similar high trajectories for an unhealthy lifestyle pattern of discretionary food consumption and television viewing time, and low trajectories for a healthy lifestyle pattern of fruit and vegetable intakes and time outdoors. The two groups however differed in BMI z score trajectories, showing stable patterns but at mean scores of 0 and +2 units, respectively. Child sex, breastfeeding duration and maternal physical activity were not associated with the identified trajectory groups. The study's authors note that the co-occurrence of stable lifestyle patterns and BMI z score trajectories in early childhood highlight the importance of initiating lifestyle obesity prevention early in life, and such interventions could target both children and the mother. A multi-behavior approach to simultaneously target healthy diet, physical activity and sedentary behaviors could be adapted. "Young children learn by imitating that which they see daily. There is no doubt that children copy the behaviors observed in the presence of parents: healthy and unhealthy," said Liliana Aguayo, PhD, MPH, a childhood obesity expert, TOS member and research assistant professor from the Hubert Department of Global Health at Emory University in Atlanta, Ga. "Evidence from this study highlights the importance of early childhood as a critical period for development of obesity. More research is needed to identify effective approaches to simultaneously address parent and child health behaviors." Aguayo was not associated with the research.     DDT exposure in grandmothers linked to obesity, earlier periods in granddaughters Young women today may face increased health risks linked to breast cancer due to effects from the banned toxic pesticide lasting over three generations University of California at Davis, April 16, 2021 In the first study to report on the health effects of exposure to a toxic environmental chemical over three human generations, a new study has found that granddaughters whose grandmothers were exposed to the pesticide DDT have higher rates of obesity and earlier first menstrual periods. This may increase the granddaughters' risk for breast cancer as well as high blood pressure, diabetes and other cardiometabolic diseases.  The research by the Public Health Institute's Child Health and Development Studies (CHDS) and the University of California at Davis was published today in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research. It suggests that effects from the pesticide DDT -- despite being banned in the U.S. nearly 50 years ago -- may contribute to the falling age of first periods and increases in obesity rates among young women today. The study found that the risk of obesity in young adult granddaughters was 2 to 3 times greater when their grandmothers (who were not overweight) had higher levels of o,p'-DDT (a contaminant of commercial DDT) in their blood during or just after pregnancy. Granddaughters were twice as likely to have earlier first menstrual periods when their grandmothers had higher o,p'-DDT blood levels. DDT and its related chemicals, including o,p'-DDT, are known to be endocrine disrupting chemicals, compounds that can alter and interfere with natural hormones that are essential for development.  "We already know that it's nearly impossible to avoid exposures to many common environmental chemicals that are endocrine disruptors. Now our study shows for the first time in people that environmental chemicals like DDT may also pose health threats to our grandchildren," said Barbara Cohn, director of CHDS and senior author of the study. "In combination with our on-going studies of DDT effects in the grandmother's and mother's generations, our work suggests we should take precautionary action on the use of other endocrine disrupting chemicals, given their potential to affect generations to come in ways we cannot anticipate today."  The Child Health and Development Studies is a unique project that has followed 20,000 pregnant women and their families for more than 60 years. CHDS enrolled and began following pregnant women in the Bay Area between 1959 and 1967, a time of high pesticide use before DDT was banned in 1972. These "founding grandmothers" in the study gave blood samples at each trimester during pregnancy and one sample shortly after birth. The blood samples were tested for levels of DDT and its related chemicals, including active ingredients, contaminants and their metabolites. The study today focused on o,p'-DDT as it has previously been linked to breast cancer, obesity and other harmful health effects in daughters, and is believed to be the most sensitive biomarker for exposures before and immediately after birth. Since granddaughters' exposure would occur via their mothers' in utero egg cell development, o,p'-DDT levels are a potential predictor of granddaughters' exposure outcomes.  "These data suggest that the disruption of endocrine systems by DDT initiates in immature human eggs, decades before the eggs are fertilized," said Michele La Merrill, associate professor at UCD who was co-lead author of the study. The CHDS study included interviews, home visits and questionnaires from the daughters and granddaughters of the original enrollees. During home visits, blood pressure and height and weight measurements were taken. The study today is based on 365 adult granddaughters who completed questionnaires, participated in a home visit, had available DDT measures from grandmothers' serum, and (for 285 of them) had available information on body mass index (BMI) in all three generations. Information on the age of first period for all three generations was available from 235 granddaughters. Previous CHDS studies have shown that mothers' DDT exposure during pregnancy or immediately after birth correlates with increased daughters' risk of breast cancer and the prevalence of breast cancer risk factors, including obesity, among adult daughters. Other prior studies have linked DDT exposure to birth defects, reduced fertility and an increased risk of diabetes. A commentary in the journal Reproductive Toxicology last year called CHDS "a national treasure that keeps on giving" and noted that "There are no other U.S. studies as well defined, sampled, and followed as the CHDS....The CHDS provides unique and essential value in understanding health effects of environmental exposures as they relate to life-stage sensitivity."       Capsaicin analog could help treatment-resistant lung cancer Small cell lung cancer cells exposed to synthetic analog of chili pepper compound responded better to chemotherapy Marshall University, April 27, 2021 A new study found that non-pungent synthetic analog of capsaicin -- the compound that makes chili peppers hot -- made small cell lung cancer cells more responsive to treatment. Small cell lung cancer is a very aggressive form of cancer with a low survival rate.  Cisplatin-based combination chemotherapy is typically the first-line treatment for small cell lung cancer patients. Although patients initially respond very well to this chemotherapy, the tumor usually comes back within a year in a form that doesn't respond to treatments. Patients with relapsed small cell lung cancer have very few treatment options.  "Irinotecan is the only FDA approved second-line drug for small cell lung cancer, but less than 3% of patients respond to it," said research team leader Piyali Dasgupta, PhD, from Marshall University. "Therefore, agents that improve the anti-cancer activity of irinotecan would be of great value to these patients." Jamie Friedman, a former doctoral student in Dasgupta's lab will present the new findings at the American Society for Investigative Pathology annual meeting during the virtual Experimental Biology (EB) 2021 meeting, to be held April 27-30.  The natural compound capsaicin has been shown to have anti-cancer effects, but its heat can also cause a burning sensation, stomach cramps, gut pain and nausea. In the new work, the researchers studied arvanil, a synthetic capsaicin analog without capsaicin's undesirable side effects.  When the researchers exposed two cisplatin-resistant lung cancer cell lines to a low concentration of arvanil, they saw no growth-inhibitory activity. However, when they treated the cells with varying concentrations of SN38 -- the active ingredient irinotecan -- they observed that the presence of arvanil greatly enhanced the ability of SN38 to slow cancer cell growth. Statistical analysis showed that the interaction between arvanil and SN38 was synergistic in nature.  "Because arvanil enhanced the anti-cancer activity of SN38 in human small cell lung cancer cells, arvanil-based combination therapies may be useful for patients with relapsed small cell lung cancer cells," said Friedman. "We hope that this work will pave the way for novel therapies for relapsed and cisplatin-resistant small cell lung cancer."     Five Therapeutic Properties of Medicinal Mushrooms GreenMedInfo, April 25, 2021   Mushrooms have recently gained popularity in culinary circles, but their far-reaching therapeutic properties should get your attention for a longer and healthier life. Although mushrooms have been part of the healer’s toolbox since ancient times, the medicinal power of mushrooms is gaining momentum in evidence-based journals. Medicinal mushrooms come in a wide variety and shapes such as white button, reishi, maitake, shiitake, oyster, cordyceps, cauliflower, tiger tail and lion’s mane, and most have health benefits that range from fighting cancer and boosting your immunity and memory to preventing diseases like diabetes and arthritis. 1. Anticancer Reishi (in Japanese) or lingzhi (in Chinese) mushrooms are well known in Asia for their anticancer properties. In a meta-analysis by scientists of 23 trials involving 4,246 cancer patients, reishi mushrooms enhanced longevity and quality of life in cancer patients.[i] Therapy with white button mushrooms impacted prostate-specific antigen (PSA) levels and inhibited prostate cancer by decreasing immunosuppressive factors.[ii] Polysaccharides from Cordyceps cicadae mushrooms inhibited the growth of cancer cells and induced cancer cell deaths showing its effectiveness as a low cost and safe treatment for cervical cancer.[iii] A peptide from the shiitake mushroom showed promising results in growth arrest, cell death and cleaning out damaged cells in a breast cancer in vitro study.[iv] In both in vitro and in vivo studies, results showed that mice with induced testicular cancer treated with the Cordyceps sinensis mushroom had significantly smaller and fewer tumors than the control group.[v] Cordyceps cicadae mushroom treatment prevented testicular damage and tumors caused by the chemotherapy drug cisplatin via inhibition of oxidative stress and inflammation in rats.[vi] In a lung cancer-induced study of mice, treatment with reishi mushrooms inhibited cell viability and mobility of lung cancer cells in vitro.[vii] In a cell study of reishi mushroom extract, the treatment offered high antitumor and liver protection with low toxicity on human liver cancer cells.[viii] 2. Immunomodulatory In a meta-analysis of 20 animal disease studies, grifola frondosa, or maitake mushroom, polysaccharide showed strong immune function by enhancing T cells, natural killer cells and macrophages in mice and increasing the secretion of two important immune factors, TNF-α and INF-γ.[ix] In a clinical study of 105 cancer patients undergoing chemotherapy or radiation treatments, a combination of reishi mushroom extract and geraniums improved immunity and fought the cancer and secondary infections that could have compromised treatment and health.[x] In a study of 18 patients diagnosed with low and intermediate myelodysplastic syndrome, which can lead to leukemia if not managed well, maitake mushroom extract treatment of three milligrams (mg) twice a day for 12 weeks increased immunity, positively affecting neutrophil, monocyte and free radical production.[xi] In a clinical study of asymptomatic children from 3 to 5 years old, treatment with beta glucans from reishi mushrooms showed increased immune system cells in the peripheral blood — signaling a strong defense against childhood infections.[xii] Reviewing in vivo and in vitro studies on mice and human cell lines using lion’s mane (Hericium erinaceus) and tiger tail (Trametes versicolor) mushrooms, treatments showed immunomodulatory, anticancer, anti-inflammatory and neuroregenerative effects.[xiii] 3. Antioxidant Polysaccharide beta glucan extracted from reishi mushroom was shown to be a powerful antioxidant in 37 high risk and 34 stable angina patients; those who were treated with 750 mg per day for three months had significantly decreased oxidative radicals and improved progression of atherosclerosis.[xiv] In a study of 42 healthy subjects, another intervention with beta glucan from reishi mushrooms of 225 mg per day for three months demonstrated its antioxidative effects — enhanced total antioxidant capacity and enzyme activities as well as reduced mild fatty liver condition to normal by suppressing oxidative stress were observed.[xv] 4. Anti-inflammatory  Crohn’s disease is a chronic inflammatory disease of the gastrointestinal tract. Treatment with a triterpene compound from reishi mushrooms showed that the inflammatory cytokines were significantly inhibited in a study of children with Crohn’s disease.[xvi] Sixty patients with moderate persistent asthma were studied and those who took the cordyceps sinensis mushroom capsule for two months had reduced airway inflammation caused by their chronic asthma.[xvii] Cordycepin from medicinal mushrooms showed strong effects on many anti-inflammatory diseases.[xviii] In a study of 32 patients with active rheumatoid arthritis, supplementation of medicinal mushroom and Chinese herbs — reishi (4 grams) and San Miao San (2.4 grams) daily — lowered arthritic pain for patients.[xix] The data in a mice study support a model where white button mushrooms regulate immunity in vitro and protect the colon from inflammation-induced injuries in vivo.[xx] The brain is susceptible to inflammation as well. In an Alzheimer’s disease model of rats, treatment with medicinal mushroom extracts delayed disease progression, improved learning and memory functions and stopped neural cell deaths and brain atrophy.[xxi] Chaga mushrooms administered to mice successfully protected against Alzheimer’s disease by modulating oxidative stress, Nrf2 signaling and mitochondrial cell deaths while improving memory and cognition.[xxii] Cordycepin from the Cordyceps sinensis mushroom alleviated Parkinson’s disease motor disorder symptoms by lowering oxidative stress and inflammation in vivo and in vitro.[xxiii] Lion’s mane mushrooms were supplemented for 12 weeks and were effective in preventing dementia and cognitive decline.[xxiv] Lion’s mane supplementation for four weeks in a study of 30 females also reduced depression and anxiety.[xxv] 5. Antidiabetic Dyslipidemia, high blood cholesterol and triglycerides is often a harbinger of future diabetes. In a rat model, white button mushrooms and a probiotic were found to lower dyslipidemia and decrease oxidative stress.[xxvi] In a study of 89 diabetic patients, oyster mushroom consumption significantly reduced blood glucose, blood pressure, triglycerides and cholesterol without ill effects on the liver or kidneys.[xxvii] Polyphenols from Phellinus igniarius, or willow bracket, mushroom extract were used in vitro and in vivo studies of induced Type 2 diabetes mice and showed improved glucose tolerance, reduced hyperglycemia and normalized insulin levels.[xxviii] Diabetic nephropathy, kidney disease caused by Type 2 diabetes, was studied in vitro with disease-induced rats and treatment with Cordyceps cicadae resulted in improved insulin resistance and glucose tolerance, suppressed inflammation and balanced gut microbiome thus stopping the diabetes-related progression of renal disease and tumors.[xxix] In an animal study, maitake mushroom prevented the progression of kidney fibrosis in diabetic nephropathy rats, significantly decreased fasting blood glucose levels, reduced inflammatory cytokines and lowered renal fibrosis indexes indicating its effectiveness in the treatment or prevention of nephropathy.[xxx] In their meta-analysis of 623 articles and 33 randomized controlled experiments using cauliflower mushroom extract (S. Crispa), researchers found statistically significant differences in diabetic symptoms including decreased serum insulin levels and wound rates and an increase in nutrient intake content.[xxxi] Mushrooms and Their Medicinal Powers Medicinal mushrooms are widely researched and used as treatment in the prevention and progression of many diseases from cancer and asthma to diabetes and dementia. Mushrooms protect you due to their anti-inflammatory, antitumor, antidiabetic, immune boosting and antioxidant activities. To learn more, see GreenMedInfo.com’s database on mushrooms.          

The Foundations of #OncoPharm series returns with all the must-know information for irinotecan.

Read the related article "Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve Outcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group" on JCO.org This JCO podcast provides observations and commentary on the JCO article “addition of vincristine, irinotecan to vincristine, dactinomycin and cyclophosphamide does not improve outcome for intermediate risk rhabdomyosarcoma a report from the Children’s Oncology Group by Hawkins, et al.” My name is Alberto Pappo and I am a pediatric oncologist and Head of the Division of Solid Tumors at St Jude Children’s Research Hospital in Memphis, Tennessee. Investigators of the Children’s Oncology Group (COG) developed a prospective randomized study to improve the outcome of patients with intermediate risk rhabdomyosarcoma by comparing the addition of the doublet vincristine and irinotecan (which will be called the irinotecan arm) to standard vincristine actinomycin D and cyclophosphamide (which will be called the VAC arm) to VAC chemotherapy only. Intermediate risk disease comprises the largest subgroup of patients with rhabdomyosarcoma and comprises patients with embryonal histology who present with tumors that are non-metastatic and unresected and arise in unfavorable sites as well as patients who present with non-metastatic alveolar histology tumors. The authors nicely review prior failed strategies that were aimed at increasing the outcome of this group of patients including dose intensification of active agents as well as the  addition of novel agents such as ifosfamide, etoposide and topotecan. 1-3 Irinotecan is a prodrug that is converted to its active metabolite SN38 and inhibits topoisomerase I. In a front-line trial for patients with metastatic rhabdomyosarcoma demonstrated a high level of activity with a 70% early response rate and an 8% disease progression rate.4 Based strong preclinical and clinical data, this agent was incorporated into an upfront randomized trial for rhabdomyosarcoma testing the benefit of adding vincristine and irinotecan to standard VAC in intermediate risk rhabdomyosarcoma. Eligibility criteria included patients with embryonal rhabdomyosarcoma who had stage II and III clinical Group 3 disease and any alveolar rhabdomyosarcoma without evidence of distant metastases.  During the first 12 weeks the two treatments were identical in duration of schedule with the exception of the substitution of irinotecan for dactinomycin and cyclophosphamide at week 4 and for cyclophosphamide at week 7 and 10 in the irinotecan arm.  During the next 30 weeks irinotecan replaced actinomycin D and cyclophosphamide at weeks 16, 19, 25, 31 and 37 in irinotecan arm.  Patients were evaluated for response at week 15, 30 and at the end of therapy.  Radiation therapy unlike the prior COG D9803 trial  started early at week 4 instead of 12 and the dose was determined by the clinical group and histology with doses ranging to 36 Gy for those with clinical group I and II to 50.4Gy for those with Group III disease. The study was designed with an 80% power to detect an overall increase in the long term event-free survival from 65% with VAC chemotherapy to 76% with the doublet VAC VI with a sample size of 486 patients.   Between December 2006 and December 2012 there were 481 patients enrolled on the study of whom 33 were ineligible.  Of the remaining 448 eligible patients 222 were randomized to VAC and 226 were randomized to the irinotecan arm.  The patient’s characteristics were similar between both arms and to other COG trials. There was a slight predominance of males, 61% of patients were between 1 and 10 years of age and 71% were Caucasian.  Embryonal rhabdomyosarcoma was the predominant histology seen in 53% of the patients and 86% had clinical Group III disease. The most common primary site was parameningeal followed by bladder prostate, extremity and retroperitoneum.    With a median followup for surviving patients of 4.8 years the estimated 4 year event-free survival was 63% for the VAC arm and 59% for the irinotecan arm.  The estimated 4 year overall survival rates was 73% for the VAC arm and 72% for the irinotecan arm. There were no differences in radiographic response among clinical Group III patients as assessed by institutional report by week 15 and no evidence of differences in outcome by treatment arm in the histologic subgroup analysis.  When compared to the previous trial D9083 which had slightly different eligibility criteria, there were no differences in event and overall survival for patients with alveolar rhabdomyosarcoma. However, patients with embryonal tumors had an inferior 4 year event-free survival in this trial when compared to patients in D9803 although the 4 year overall survival rates were similar.  The vast majority of treatment failures were due to tumor progression or recurrence. The 4 year local failure rate was 22.4%, the 4 year regional lymph node failure rate was 5.7% and the 4 year distant failure rate was 18%.  Hematologic toxicity and febrile neutropenia were more commonly observed in the VAC arm whereas diarrhea and mucositis were more prevalent in the irinotecan arm. Hepatopathy was more common in the VAC arm and patients in the irinotecan arms who developed grade 3 4 diarrhea were more likely to carry the UGT1A1  7/7 genotype.  The authors conclude that the addition of vincristine and irinotecan to a VAC backbone failed to improve the outcome of patients with intermediate risk rhabdomyosarcoma. However, the lower cumulative doses of cyclophosphamide in the irinotecan arm which could potentially reduce the risk of infertility in selected patients and the lower rates of hematologic toxicity in this regimen have provided a rationale for the COG to use a VAC irinotecan backbone in their current up front randomized trial for intermediate risk rhabdomyosarcoma.   This trial highlights the lack of significant advances in the therapy of pediatric rhabdomyosarcoma despite the fact that irinotecan showed significant preclinical and clinical activity in metastatic patients with this disease.5,6 Similarly, in a previous study, the addition of another camptothecin, topotecan failed to improve the outcome of intermediate risk patients despite promising clinical activity in newly diagnosed metastatic patients 7suggesting that identification of novel agents based on their activity in  phase II window studies for high risk rhabdomyosarcoma is not an optimal method for selecting active compounds that could be incorporated into front-line studies for intermediate risk disease. As suggested by the authors of the paper just discussed, other novel mechanisms of drug testing such as randomized phase II studies in recurrent disease might offer alternative more effective strategies for identifying agents to be tested in intermediate risk patients. In contrast to this results, the European Pediatric Soft Tissue Sarcoma Study Group has recently reported at the ASCO 2018 meeting improved outcomes for a similar population of patients when maintenance therapy with low dose cyclophosphamide and vinorelbine is added to a backbone of vincristine, ifosfamide and actinomycin D (VAI). 8  In this trial, patients with non metastatic incompletely resected embryonal rhabdomyosarcoma arising in unfavorable sites and localized alveolar rhabdomyosarcoma without nodal metastases who achieved a complete remission after 9 cycles (27 weeks) of VAI with or without doxorubicin were randomized to stop treatment or receive maintenance chemotherapy with six 28 days cycle of vinorelbine and cyclophosphamide.  The study was initially designed with an 80% power to detect an increase in the 3 year EFS from 55% to 65% with a hazard ratio of 0.67 but was then amended to allow detection of a relativity reduction rate in the relapse rate of 50%.  This trial accrued 670 patients of whom 371 were eligible and 186 were assigned to the standard arm and 185 to the maintenance arm.  The clinical features were well balanced between the two groups. With median follow up of 5 years in surviving pts, the 3 year event-free survival and overall survival in the maintenance arm and the standard arm were  78.4% vs 72.3% (p value 0.061) and 87.3% vs. 77.4 (p value = 0.011).  The investigators concluded that the addition of maintenance therapy is a novel strategy that improves the outcome of this group of patients with rhabdomyosarcoma and establishes the new standard of care for patients in Europe.  The results of this trial however, need to be interpreted with caution and cannot be generalized. The follow-up of patients is relatively short and only those who achieved a complete radiographic response after chemotherapy were eligible to be randomized, no information was provided regarding outcomes of patients who were randomized to receive doxorubicin, there are only 9 cycles of chemotherapy given prior to randomization to maintenance therapy whereas the COG studies give 14 cycles of therapy and finally, there are slight differences in the eligibility criteria when compared to the previous COG  trials.    In conclusion, the addition of an irinotecan backbone to standard VAC chemotherapy does not improve the outcome of patients with intermediate risk rhabdomyosarcoma. However, the irinotecan containing regimen offers potential advantages such as outpatient administration of chemotherapy, reduced hematologic toxicity and cumulative cyclophosphamide exposure and has therefore become the standard backbone for patients with intermediate risk rhabdomyosarcoma in the United States.  This concludes this JCO podcast.  Thank you for listening.    

In June 2013 I was diagnosed with pancreatic cancer. Pancreatic cancer is a very difficult cancer, with a five-year survival rate of only seven percent. The only potential cure for pancreatic cancer is a harsh operation, called a “Whipple,” in which parts of the pancreas and other organs are removed, and the remaining organs are sewn together. After chemotherapy and radiation I became eligible for the surgery, which was performed in March 2014. The surgery was successful, and all of the visible cancer was removed. But even when it appears that all the cancer has been removed by surgery, pancreatic cancer frequently recurs. The cancer returned In August 2014, and my doctors determined that it had spread elsewhere in my body. I then went on a year of rigorous chemotherapy which made the tumors disappear on scans. In August 2015 I went on a lighter, maintenance chemotherapy. Still, months later, the cancer is not visible on scans.I told my story to an event sponsored by the Miami affiliate of the Pancreatic Cancer Action Network. The video of my talk is online (https://youtu.be/cVZ3Ls9H2gc).Cancer and Genetic MutationsJournal entry by Robert Glazier — 11/5/2016Long ago all diseases of a certain type were linked together as “cancer.” Over time, doctors recognized that different cancers are different diseases: for example, prostate cancer is different from pancreatic cancer, with different treatments and different prognoses. More recently, doctors have began to understand that a person’s genetic profile can sometimes be the basis for treating a person with a disease that starts in a particular location based on the person’s genetic mutations, rather than solely the place of origin. Not all pancreatic cancers, for example, are alike. This is known as personalized medicine.Personalized medicine is in its early stages, and has not yet found much information useful for the treatment of pancreatic cancer. But there is some. Let me explain. Over the last few years I have learned that I suffer from two unusual conditions.First, I have Gilbert’s Syndrome. This condition, which about 3% to 12% of people have, means that my body does not process bilirubin as well as it should. This isn’t much of a problem. It simply means that for me a slightly elevated bilirubin level is not something to be concerned about, as it would be with most people.Second, I have an unusually toxic reaction to one of the drugs in Folfirinox, the chemotherapy regimen I was on for a year. The drug is called Irinotecan. I learned this from experience—I had miserable diarrhea, which disappeared when they removed the Irinotecan. After they did this I had genetic testing of my tumor, and it disclosed that I have a genetic mutation which would make the drug toxic for me.This week I learned that these two conditions—my high bilirubin levels and my toxic reaction to Irinotecan—are linked. They are both caused by the same genetic mututation, known as UGT1A1. Scientists hope that with time they will discover effective treatments for pancreatic cancer based on genetic mutations. I hope that I am around to benefit from those advances.

April 25, 2011 In this third episode, host Tim Cripe, MD, PhD, asks his co-hosts to discuss two recent papers that provide new information about genetic predisposition to increased toxicity to vincristine in some children, and the results of a phase II study using a combination therapy (irinotecan and temozolomide) in relapsed or refractory neuroblastoma. 1:24 Maureen O'Brien, MD discusses "Increased risk of vincristine neurotoxicity associated with low CYP3A5 expression genotype in children with acute lymphoblastic leukemia" in Pediatr Blood Cancer. 2011 Mar;56(3):361-7. doi: 10.1002/pbc.22845. Epub 2010 Nov 11.http://www.ncbi.nlm.nih.gov/pubmed/21225912 22:10 Lars Wagner, MD discusses "Phase II study of irinotecan and temozolomide in children with relapsed or refractory neuroblastoma: a Children's Oncology Group study" from J Clin Oncol. 2011 Jan 10;29(2):208-13. Epub 2010 Nov 29. http://www.ncbi.nlm.nih.gov/pubmed/21115869

Dr. Colin Weekes, pancreatic cancer specialist from the University of Colorado, discusses the history of and recent developments in chemotherapy for metastatic pancreatic cancer.

Dr. Colin Weekes, pancreatic cancer specialist from the University of Colorado, discusses the history of and recent developments in chemotherapy for metastatic pancreatic cancer.

Dr. Colin Weekes, pancreatic cancer specialist from the University of Colorado, discusses the history of and recent developments in chemotherapy for metastatic pancreatic cancer.

Dr. Colin Weekes, pancreatic cancer specialist from the University of Colorado, discusses the history of and recent developments in chemotherapy for metastatic pancreatic cancer.

Dr. Colin Weekes, pancreatic cancer specialist from the University of Colorado, discusses the history of and recent developments in chemotherapy for metastatic pancreatic cancer.

Dr. Colin Weekes, pancreatic cancer specialist from the University of Colorado, discusses the history of and recent developments in chemotherapy for metastatic pancreatic cancer.

Dr. Mark Socinski reviews key results in small cell lung cancer (SCLC) from ASCO 2012, including the SWOG 0802 trial of topotecan +/- VEGF inhibitor aflibercept and a Japanese randomized trial of cisplatin/amrubicin vs. cisplatin/irinotecan.

Dr. Mark Socinski reviews key results in small cell lung cancer (SCLC) from ASCO 2012, including the SWOG 0802 trial of topotecan +/- VEGF inhibitor aflibercept and a Japanese randomized trial of cisplatin/amrubicin vs. cisplatin/irinotecan.

Background: Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question whether this statement holds true also for bevacizumab-based first-line treatment including escalation-and de-escalation strategies. Methods/Design: The AIO KRK 0110/ML22011 trial is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m(2) bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m(2) BID for 14d (d1-14), irinotecan 200 mg/m(2) (d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumour tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are overall response rate (ORR), overall survival, progression-free survival, safety and quality of life. Conclusion: The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with combination chemotherapy (CAPIRI-Bev) and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary.

Objectives: Bevacizumab is a monoclonal antibody that directly inhibits vascular endothelial growth factor, a key regulator of angiogenesis. Bevacizumab significantly improves progression-free and/or overall survival in metastatic colorectal cancer in combination with standard chemotherapy. This review describes the evolution of irinotecan-based regimens for metastatic colorectal cancer and evaluates the addition of bevacizumab to these regimens. Methods: Literature searches from large publication databases (PubMed, ASCO, ASCO GI, ESMO) were performed to capture key data relevant to bevacizumab, irinotecan, and the treatment of colorectal cancer. Results: Data from numerous large, multinational studies support the addition of bevacizumab to irinotecan-containing chemotherapy regimens for further improvement in patient outcomes. In a randomized, placebo-controlled trial, addition of bevacizumab to irinotecan significantly improved progression-free survival, overall survival and response rate in patients with metastatic colorectal cancer, and these results are supported by a number of other clinical trials and observational studies. Furthermore, the addition of bevacizumab to irinotecan improves outcomes regardless of K-ras mutational status. Bevacizumab has a well-established safety profile and the toxicities associated with its use are usually mild in severity and easily manageable. Conclusions: Addition of bevacizumab to irinotecan-containing regimens is an effective therapy option for the treatment of metastatic colorectal cancer. Copyright (C) 2010 S. Karger AG, Basel

Oncology Times Broadcast News: Metastatic Colorectal Cancer: Capecitabine Equivalent to 5-FU in Irinotecan/Bevacizumab Combos Adding the oral drug capecitabine to a regimen of bevacizumab plus irinotecan was as effective as adding infusions of 5FU/folinic acid for patients who had metastatic colorectal cancer in a phase II study presented to the World Congress on Gastrointestinal Cancer in Barcelona (24-27 June, 2009; Abstract: 0-0013). Michel Ducreux, Head of the Gastrointestinal Service at the Institut Gustave Roussy in Villejuif, Paris, discussed the new evidence and its clinical implications with Peter Goodwin.

Michel Ducreux, Head of the GI Service at Institut Gustave Roussy, talks about the new evidence and its clinical implications, as reported in his Phase II study at the ESMO World Congress on Gastrointestinal Cancer.

Michel Ducreux, Head of the GI Service at Institut Gustave Roussy, talks about the new evidence and its clinical implications, as reported in his Phase II study at the ESMO World Congress on Gastrointestinal Cancer.

Background: The cytotoxic treatment of patients suffering from advanced or metastatic cancer undergoing hemodialysis due to chronic renal failure still remains a problem, since for those patients pharmacokinetic and pharmacodynamic data on most cytotoxic agents are lacking. Case Report: We report a 45-year-old male who suffered from chronic renal failure and was diagnosed with stage-3 colorectal cancer (CRC) in February 2000. After surgical removal of the tumor an adjuvant chemotherapy of dose-reduced i.v. bolus 5-fluorouracil and folinic acid was begun (Mayo protocol). Due to excessive gastrointestinal toxicity, therapy was discontinued after the first cycle. In April 2000 liver metastases were diagnosed. The patient was then put on a weekly schedule of dose-reduced CPT-11 (50 mg/m(2), 80 mg total). No hematological or non-hematological toxicity grade 3/4 was observed. Due to excellent tolerability and lack of severe side effects the dose was increased up to 80 mg/m2 (140 mg total) weekly. A dose escalation to 100 mg/m(2) (180 mg total) resulted in severe diarrhea (grade 4). Within 2 months of treatment the patient achieved a lasting partial remission until April 2001 (12 months). A significant progression of hepatic metastases required an alternative treatment regimen beginning in July 2001 (HAI, hepatic artery infusion). Conclusion: This case report demonstrates the feasibility and efficacy of a weekly treatment with dose-reduced CPT-11 in a patient with metastatic CRC on hemodialysis due to chronic renal failure.