Podcasts about Vincristine

At age two, Jon Brent was diagnosed with a type of blood cancer, acute lymphoblastic leukemia.  He underwent an aggressive chemotherapy regimen, including vincristine, dexamethasone, methotrexate and prednisone, but after that still needed a bone marrow transplant.  He has achieved survivorship but is still in pain and expects to some extent he will be for the rest of his life.  Jon can no longer compete in contact sports but is an active participant in ultimate Frisbee.

In this JCO Article Insights episode, Alexandra Rojek provides a summary on "Romidepsin Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Versus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Final Analysis of the Ro-CHOP Trial" by Camus et al published February 16th, 2024 and the associated editorial written by Dr. Mehta-Shah and Dr. Horwitz. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Alexandra Rojek: Hello and welcome to JCO Article Insights. I'm your host, Alexandra Rojek, and today we will be discussing a clinical trial update published in the May 10th issue of JCO addressing the long term follow up of the addition of romidepsin to CHOP chemotherapy for previously untreated peripheral T-cell lymphoma, or PTCL. This report by Camus et al discusses a five-year follow up of the original Ro-CHOP trial, which did not meet its primary endpoint of progression free survival. The original Ro-CHOP study, conducted by the LYSA group, was published in 2021 in JCO and was conducted as a one-to-one randomized phase III study of Ro-CHOP versus CHOP for patients aged 18 to 80 years with PTCL. 98 international centers were included, and the study enrolled patients between 2013 and ‘17. Nodal follicular helper T-cell, or TFH lymphoma was defined in this study follow-up as a PTCL expressing at least two of five TFH markers according to the latest classifications. The study's primary endpoint was PFS with secondary endpoints of OS and duration of response, or DOR. Five year follow up was reached in December 2022. In the original study report, the addition of romidepsin to CHOP did result in a reduction of dose intensity of chemotherapy. However, in this updated follow up, there were no new safety signals reported. A total of 421 patients were enrolled in the trial with a median age of 65 years. Notably, those who were randomized to the Ro-CHOP arm had a higher proportion of IPI 4-5 scores at 33%, versus 24% of those who were assigned to CHOP alone despite randomization. Nearly half of patients carried a histologic diagnosis of angioimmunoblastic T-cell lymphoma. 30% were characterized as PTCL NOS, not otherwise specified, 10% ALK negative anaplastic large cell lymphoma, leaving 13% reported as other. Over 60% of patients had stage four disease at enrollment, with nearly half having more than two sites of extranodal involvement. Median follow up was six years with a median PFS of 12 months for Ro-CHOP and 10.2 months for CHOP, which did not reach statistical significance as reported in the original study publication. Estimated five year OS available as a part of this clinical trial update was 50% for Ro-CHOP and 43% for CHOP alone, and also did not reach significance. There was, however, a longer duration of response observed in the Ro-CHOP arm at 52 months versus 24 months for CHOP, which is a new finding in this extended follow up of the study. In an effort to better understand whether there are subgroups which may benefit from romidepsin despite the overall negative outcome of this study, the authors are able to provide new insights from this Ro-CHOP study in line with our current and updated understanding of PTCL. When the authors evaluated the study population for subgroups which may benefit from addition of romidepsin, TFH lymphomas, which included angioimmunoblastic, follicular, and NOS subtypes, were noted to have an improved response to the addition of this HDAC inhibitor. This subgroup, numbering 201 patients, experienced a mean PFS of over 19 months with Ro-CHOP versus over 10 months for those who received CHOP, and this difference achieved statistical significance. Similarly, there was a higher complete response rate and longer duration of response for those in the TFH subgroup who received romidepsin. The authors also make note that those patients in this subgroup with high IPI appeared to particularly benefit. However, those in the PTCL NOS group who did not fit the TFH subtype experienced poor outcomes with shorter PFS and OS as compared to other histologic subtypes, which is in line with other reported data in the field. The authors in this update also report on treatments and outcomes after first progression or relapse of disease, which includes a total of 274 patients, of whom 251 received second line therapy. The median PFS in OS after progression or relapse was only 3.3 months and 11.5 months, respectively, and again, patients with the TFH subtype experienced a longer median OS than other included histologies. Only 8% of patients proceeded to undergo autologous stem cell transplantation overall, and 5% underwent allogeneic stem cell transplantation. While the authors note that they did not observe any notable outcome differences between various included second line therapies, they do note of a possible benefit of the antibody drug conjugate brentuximab vedotin or BV in combination with chemotherapy backbones. Those who received a BV containing regimen in the second line experienced a better CR rate and a longer PFS, too. However, the OS too was not significantly different. Again, the authors note that most of the benefit of the addition of BV to chemotherapy in the second line appeared focused on this TFH lymphoma subgroup. Of note, CD30 status was not recorded as a part of the study for included patients and could not be further reported on. The findings of the authors present in this subgroup analysis of the negative Ro-CHOP study seek to find benefit in future lessons for patients with these rare lymphomas who do not have a multitude of effective treatments available to them. The subgroup benefit in this clinical trial update based on the TFH phenotype fits our evolving understanding of PTCL in the modern era. Mutations characteristic of the TFH subgroup, in this case often involved in chromatin modification and the tumor microenvironment, have been linked to improved responses when treating with epigenetic targeting drugs such as romidepsin, thus making the findings of TFH lymphoma in the Ro-CHOP trial confirmatory of what we would expect from correlative studies. Despite the benefit of Ro-CHOP for those with TFH lymphoma, this updated analysis of a major frontline study of PTCL highlights the critical need in the T-cell lymphoma field to, first of all, better understand and separate what we have come to recognize as the heterogeneous diseases historically lumped together as PTCL. This historic classification, based on a lack of deeper molecular understanding of disease biology is unlikely to represent the true biologic diversity of its component subtypes, including the focus on TFH lymphoma presented here. The second critical unmet need, which this subgroup analysis highlights, is the need to investigate the benefit of new therapeutic agents in these distinct subgroups of PTCL, where the need for improved survival outcomes is sorely needed when examining historical outcomes with currently available therapies, both in the frontline setting as well as those in the relapsed refractory group. The associated editorial, written by Dr. Mehta-Shah and Dr. Horwitz, elegantly discusses the challenges of designing studies in rare diseases such as PTCL, which are both biologically informed as well as appropriately powered. As the authors discuss, it is rare to get a second chance for a drug, as is the case for romidepsin, where these negative results led to its voluntary withdrawal in PTCL, affecting availability of the drug for patients in the relapsed setting, as well as future clinical trials, which could have had potential for success. Additionally, better understanding of the biological underpinnings of PTCL needs to lead to better designed and appropriately powered clinical trials, as these subsets of patients are in great need of therapeutic advances. While none of these tasks is easy nor straightforward, this clinical trial update of the RoCHOP study suggests a path forward from learning from prior, promising yet failed attempts at moving the standard of care for frontline therapy of T-cell lymphoma forward. This is Alexandra Rojek thank you for listening to JCO Article Insights. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at ascp.org/podcasts. 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.  

Chest pains and severe fatigue drove Valerie David to seek medical attention, which led to a diagnosis of Stage 3B Cell Diffuse Large Cell Non-Hodgkin's Lymphoma.  A chemotherapy regimen helped her achieve survivorship.  However, years later, she discovered a lump under her armpit.  After getting it checked out, she was diagnosed with Stage 2 Invasive Lobular Carcinoma, a form of breast cancer. Again, aided by a chemotherapy regimen, Valerie survived this diagnosis, but not long after that, she was diagnosed with Stage 4 metastatic breast cancer.  Despite the staging, Valerie was prescribed a less aggressive form of chemotherapy, and survived.  Inspired by her cancer journey, she written and starred in an award-winning one-woman play, “The Pink Hulk,” seen through the United States and in Europe.

In episode 60 of the Summits Podcast, Vince Todd, Jr. is joined by Dr. Jenny Belsky of Riley Hospital for Children. Tune in as Dr. Belsky shares her research on decreasing the detrimental side effects children and teens experience while receiving cancer therapy, now funded by the Heroes Foundation Team JOEY fund. For more on Dr. Belsky's research, visit https://www.heroesfoundation.org/pediatric-cancer-researcher-will-use-30k-from-team-joey-to-make-patient-journeys-less-painful/. Subscribe to the audio version of the Summits Podcast https://summitspodcast.fireside.fm Find out more about the Heroes Foundation https://www.heroesfoundation.org Find out more about The Brookfield Group https://thebrookfieldgroup.com Discover Platform 24 co-working https://www.platform24.co What's your cancer story? Hosted by cancer survivor and philanthropist Vince Todd, Jr., Chairman and Co-Founder of the Heroes Foundation, and Heroes Foundation Board Member Daniel Abdallah, the Summits Podcast is a place for people to share their stories. Everyone has a cancer story. From battling a deadly disease to caring for a loved one, when we rise up and face life's greatest challenges, we see with a new vision, feel with a greater passion, and think with a deeper perspective. Along the way, paths cross, journeys intersect, and missions converge. For Vince Todd, it was his own cancer diagnosis that led him and his wife, Cindy, to launch the Heroes Foundation to provide meaningful support to cancer patients, education to promote cancer prevention, and resources to advance research for a cure. What started with friends and family grew into a community. The Summits Podcast is an extension of that community. Our stories are what bring us together. Artists, athletes, doctors, business people - we're all family members, community leaders, and activists. Everyone has a story. Anyone can inspire. No one battles alone. Join the conversation. Let's climb the summit together.

In this week's episode we will review no survival benefit for vincristine/steroid pulses in contemporary studies of childhood acute lymphoblastic leukemia (or ALL). Next, the rheumatology drug abatacept may be a promising strategy for the treatment of acute graft-versus-host disease (or GVHD). Finally, we'll discuss the hemorrhage risk of dasatinib therapy.

Dr. Paul Crane discusses Vincristine-induced neuropathy. This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.  

After an incorrect diagnosis of Mild Cerebral Palsy,  Jamie McElhatton's  now 8 year old son Max was diagnosed with the Pediatric Brain Cancer Pilositic Astrocytoma in 2018. Jamie will talk about his son and about a 60 minutes piece that aired on May 22nd by Bill Whitaker that talked about the drugs Vincristine and Vinblastine, and the shortages of each of these drugs that are important to Pediatric Cancer patients. 

In part one of a two-part episode, Bernie Marini and Anthony Perissinotti take a journey through the history of acute lymphoblastic leukemia treatment throughout the decades and explain how we got to our current standard of care treatment of ALL patients. In part 2 we tackle the UKALL14 study evaluating the addition of rituximab to acute lymphoblastic leukemia therapy. Some important historical articles that we reference: Nitrogen mustard therapy: https://pubmed.ncbi.nlm.nih.gov/20997191/ Methotrexate/Aminopterin: https://www.nejm.org/doi/full/10.1056/nejm194806032382301 Vincristine: https://pubmed.ncbi.nlm.nih.gov/13627916/ and https://pubmed.ncbi.nlm.nih.gov/2085431/ and https://www.utpjournals.press/doi/pdf/10.3138/cbmh.17.1.155 6-MP: https://pubmed.ncbi.nlm.nih.gov/13105700/ Total Therapy: https://pubmed.ncbi.nlm.nih.gov/5237796/ and https://pubmed.ncbi.nlm.nih.gov/5279904/ BFM: https://pubmed.ncbi.nlm.nih.gov/320377/ and https://pubmed.ncbi.nlm.nih.gov/23700050/ This episode is dedicated to the late Don Pinkel (9/7/1927 - 3/9/2022), a pioneer in the treatment of childhood ALL. Read more about his legacy here: https://cancerletter.com/obituary/20220318_4/ and https://www.nature.com/articles/s41375-022-01562-9.pdf and https://www.smithsonianmag.com/innovation/childhood-leukemia-untreatable-dr-don-pinkel-st-jude-180959501/

Welcome to the first ever episode of The Underdog Vet Podcast! I am ridiculously excited for you to hear this episode. For the very first 'Animal Advocate Interview' I chatted with the inspirational Michael Baines. A chef by profession but a dog rescuer by choice Michael left his native Sweden and moved to Thailand in 2002 where he has become known as the man that rescues dogs. Michael is the President and Co-Founder of The Man That Rescues Dogs Foundation. Since it was established in 2011 the Foundation has grown massively and now cares for more than 1000 dogs. It has taken over the running of the local government dog shelter and has a fully equipped free of charge veterinary clinic. Michael and I talked about how he got into rescuing dogs, how the Foundation started, living with 18 dogs in your home and of course the Wheelchair Mafia! The Foundation's work includes neutering of cats and dogs in its veterinary clinic, caring for 690 dogs in its sanctuary and feeding some 350 dogs living on the streets. They also educate the local community about keeping pets and that a pet is for life. Also 6000 Thai Baht is about £135 or USD$170. Michael used some terms some listeners may not be familiar with: TVT are Transmissible Venereal Tumours, a malignant tumour common in street dogs in Thailand (here's a link for more information on these tumours in dogs https://www.msdvetmanual.com/veterinary/dog-owners/reproductive-disorders-of-dogs/transmissible-venereal-tumor-in-dogs). Vincristine is a chemotherapy drug often used in treating cancers. Links: The Man That Rescues Dogs website: https://tmtrd.org/ The Man That Rescues Dogs Facebook Page: https://tmtrd.org/ Facebook page: https://www.facebook.com/tmtrdorg/ The Man That Rescues Dogs Instagram page: https://instagram.com/themanthatrescuesdogs?utm_medium=copy_link How you can help: https://tmtrd.org/how-you-can-help/ Clips: The Wheelchair Mafia on Instagram: https://www.instagram.com/reel/CUPeDGSsqrc/?utm_medium=copy_link The Wheelchair Mafia on Facebook: https://fb.watch/c07KPsR0wI/ Clip that went viral in 2015 mentioned by Michael: https://fb.watch/bNO-H-2Axs/ The Wheelchair company Michael uses for The Wheelchair Mafia: https://www.handicappedpets.com/ --- Send in a voice message: https://anchor.fm/the-underdog-podcast/message

On this week's episode of Fanboys, Edgar and Ty blow Diego's greatest secret and successfully (?) apply lit theory to cloud rap. Grab the full episode on The Hard Times' Patreon! (https://patreon.com/thehardtimes) ALSO: are you in a shitty band? Want to hear the Fanboys try to say something nice about it? Submit your music to Edgar's Twitter (https://twitter.com/EdgarTowner)! Be sure to check out this week's featured artists: Stribling Way (https://open.spotify.com/album/2wXhWEGoopA9lZ7WXuFfZA?si=MqF2_G0DRn2Rf6o0jlvXgQ&nd=1), Moses Atlas Gold (https://soundcloud.com/frank-moses-332593052/sets/the-decision?si=a4432c28a05d4e6296507ac6779c112a&utm_source=clipboard&utm_medium=text&utm_campaign=social_sharing), Ultra Dust (https://open.spotify.com/album/4jUmmvlhL9lOR7X3ywb4YK?si=SN6tE-unQiqG2Oh3NIKi0Q&nd=1), Vincristine (https://www.youtube.com/watch?v=IzSzbA6p4DI), Creation Myth (https://open.spotify.com/artist/0l2bRsTKtkRGYrqaSi3jb1?si=_GbPgYIiTSiH7YhuZnEHfQ&nd=1), and Travis Alexander (https://boaisy.com/)

An interview with Dr. Jaishri Blakeley from Johns Hopkins University School of Medicine in Baltimore, MD, and Dr. Nimish Mohile from the University of Rochester Medical Center in Rochester, NY, co-chairs on “Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline”. This guideline addresses evidence-based therapies for patients with newly diagnosed and recurrent gliomas. Read the full guideline at www.asco.org/neurooncology-guidelines.   TRANSCRIPT [MUSIC PLAYING]   SPEAKER 1: 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. SPEAKER 2: Hello, and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today, I'm interviewing Dr. Jaishri Blakeley from Johns Hopkins University School of Medicine in Baltimore, Maryland, and Dr. Nimish Mohile from the University of Rochester Medical Center in Rochester, New York, co-chairs on therapy for diffuse astrocytic and oligodendroglial tumors in adults American Society of Clinical Oncology and Society for Neuro-Oncology guideline. Thank you for being here, Dr. Blakeley and Dr. Mohile. SPEAKER 3: Thank you. SPEAKER 4: Thank you. SPEAKER 2: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with a publication of the guideline in the Journal of Clinical Oncology. Dr. Blakeley, do you have any relevant disclosures that are directly related to this guideline topic? SPEAKER 3: No, I do not. SPEAKER 2: Thank you. And Dr. Mohile, do you have any relevant disclosures that are related to this guideline topic? SPEAKER 4: No, I don't have any relevant disclosures. SPEAKER 2: Great. Thank you. Then let's get into the content of this guideline. So Dr. Mohile, can you start by giving us a general overview of the scope and purpose of this guideline? SPEAKER 4: Yeah, so over the past 10 years, there have been several positive clinical trials in various glioma subtypes, and several of them have demonstrated a benefit for chemotherapy. The primary purpose of this guideline is to help practicing clinicians understand how these trials might impact treatment for patients with gliomas. During this period, there's also been two updates to the World Health Organization classification of gliomas, and the terminology of gliomas has changed. So what we call tumors today is different from what we might have called them 10 years ago. And so a second purpose of our guideline is essentially to provide a key or a translator so a clinician can look at a pathology report today in 2021 with a current terminology and know what to do with that patient and what treatment best fits for that patient today based on what they would have been called in a trial several years ago. SPEAKER 2: Great. That makes a lot of sense. So then Dr. Blakeley, looking at this guideline, it addresses four clinical questions, which are after maximal safe surgical resection, what are the evidence-based therapies for adults with newly diagnosed glioma including optimal regimens, settings, and timing of therapy? Then also, what are the appropriate therapies for adults with recurrent glioma, including optimal regimens, settings, and timing of therapy, followed by what should the effect of MGMT promoter methylation status be on choice of therapy and if there are subpopulations that should affect the choice of therapy. I'd like to review the key recommendations for those clinical questions. In reading through the guideline, the expert panel provided recommendations based on the IDH mutation status and the diagnostic categories in the WHO 2016 and 2021 classification systems for tumors of the central nervous system. So it seems appropriate to review the recommendations in this manner as well. Starting with IDH mutant astrocytic and oligodendroglial tumors, what is recommended for patients with oligodendroglioma, IDH mutant, 1p19q deleted CNS WHO grade 2 or 3? SPEAKER 3: Absolutely, and I'll just summarize for our listeners to help simplify that as you said, essentially, all of the guidelines are divided along molecular markers. And the first cohort are 1p19q co-deleted gliomas. Something that is a 1p19q deleted gliomas also an oligodendroglioma. Those are interchangeable. If you are 1p19q co-deleted, you have oligodendroglioma and vise versa. In general, 1p19q co-deleted tumors also are IDH mutant. So you can consider that one bundle. And oligodendroglioma is something that is 1p19q co-deleted and IDH mutant. And for that whole classification, whether it's WHO grade 2 or WHO grade 3, the recommendation is for radiation followed by the combination of procarbazine, CCNU, and vincristine, based on two prospective studies that showed similar results at different time points. There are a couple of modifications to that guideline. There is a statement that if people feel that the combination of Procarbazine, CCNU, and Vincristine, also called PCV, is too toxic, they can consider temozolomide as an alternative for this subclass of tumors 1p19q co-deleted IDH mutant. And also, importantly, the 1p19q co-deleted grade 2 gliomas are some of the best performing tumors in terms of prognosis of all glial tumors and maybe all CNS tumors. And so there is a statement in the recommendations that say-- it says it is reasonable to defer therapy under appropriate circumstances. And the text goes into what those appropriate circumstances might be, including how much of a resection could be achieved, what the functional status of the person is, how old they are, et cetera. But big picture-- 1p19q co-deleted tumor equals an oligodendroglioma, and those are almost all IDH mutant. And the bottom line recommendation is radiation followed by PCV with the parentheses saying temozolomide might be a reasonable alternative to PCV, and if you have a particularly benign presentation with a grade 2 tumor, you can consider deferring that therapy start for a time. The next big bundle is astrocytic tumors that are not 1p19q co-deleted. So in the guidelines, those are termed as 1p19q non-co-deleted. And those tumors do come in two flavors-- IDH mutant or IDH wild type. And I'm going to focus on the IDH mutant because they track closer to the oligodendroglioma, but they are kind of a bridge between the very good prognosis associated with oligodendrogliomas and the more aggressive prognosis associated with malignant gliomas. And for this cohort, the 1p19q non-co-deleted IDH mutant cohort, the recommendation is for radiation therapy with adjuvant chemotherapy, and there is data that supports that adjuvant chemotherapy being either PCV or temozolomide. We don't prioritize between those two regimens. And why I'm highlighting the word adjuvant is in some centers, there is a tendency to use temozolomide concurrent with radiation therapy. And the recommendation for these 1p19q non-co-deleted IDH mutant WHO grade 2 tumors is not to use it concurrent but to use it in the adjuvant setting. And then I will round out with talking about IDH wild type. So now we're, again, 1p19q non-co-deleted but IDH wild type. Those tumors may act closer to the glioblastoma. And in that setting, we would say-- the recommendations say to treat with radiation and consider concurrent temozolomide as you would with glioblastoma or only adjuvant temozolomide as you would with the lower grade astrocytoma. SPEAKER 2: Great. Thank you for going through that and providing such clarity to those recommendations. Then following that, Dr. Mohile, moving on to glioblastoma and other IDH wild type diffuse glioma, what are the key recommendations for people with newly diagnosed glioblastoma IDH wild type CNS WHO grade 4? SPEAKER 4: So in the current classification, IDH wild type CNS World Health Organization grade 4 is what we've known of classically as glioblastoma. And for patients with glioblastoma who are fit and can tolerate therapy, we recommend treatment with radiation, concurrent temozolomide, and a six month course of adjuvant temozolomide. We also recommend that they can receive alternating electric field therapy along with the adjuvant temozolomide. Now the recommendations become a little bit more complicated for patients who might not be as fit-- so patients who might be older, have poor performance status, have other measures of frailty. And the way we wrote this is we said that if a patient who is undergoing a six week course of radiation, if that course of radiation, if the benefits did not outweigh the harm, then you could consider alternate regimens. And these include shorter courses or hypofractionated courses of radiation with or without chemotherapy and also includes courses that are chemotherapy alone. So in people who have tumors that have MGMT promoter methylation, we can consider the option of temozolomide alone. So this would be specifically for patients who either are older, more frail, who we feel are going to have difficulty going through a radiation course. There is some data to support this temozolomide alone approach. SPEAKER 2: Thank you. I appreciate you going through those recommendations very clearly as well. You clearly put a lot of effort into these recommendations. So then, Dr. Blakeley, what is recommended for patients with astrocytomas IDH wild type CNS WHO grade 2 or 3? SPEAKER 3: Yes, thank you. So as Dr. Mohile was just saying, for glioblastoma, you can really think about the recommendations for WHO grade 4 very similarly for IDH wild type independent of grade. And that is a new shift in the management of gliomas in adults. Previously, the histologic grading had a lot of weight on whether or not we would offer radiation and chemotherapy. But with the new prognostic and predictive value known associated with the IDH1 mutation or lack of mutation being IDH wild type, the recommendation is if somebody is IDH wild type CNS WHO grade 2 astrocytoma or grade 2 or grade 3, they would be offered treatment similar to a glioblastoma, which would be concurrent radiation and temozolomide followed by adjuvant temozolomide as long as performance status and all other factors support doing so. SPEAKER 2: Understood. I appreciate you providing that information as well. So were there additional areas where the expert panel found evidence either insufficient or was unable to make a recommendation? SPEAKER 4: Yeah, so there's two tumor types where we didn't have enough data to make a specific therapeutic recommendation. The first, unfortunately, is in recurrent glioblastoma. And there were no randomized controlled trials that demonstrated a benefit of one therapy over another. And so our recommendation is that when available, patients should be referred for a clinical trial. The other area is in a tumor type called diffuse midline glioma. This is a tumor characterized by the h3k27 mutation more commonly seen in children. But we do see this in adults. And here as well, there were no randomized trials that could clearly give us guidance on what the best therapy was even in the newly diagnosed setting. And our recommendation here also was, if available, to be considering a clinical trial. SPEAKER 2: Understood. It's important to recognize where there are areas where we're lacking evidence as well. So then, Dr. Blakeley, in your view, why is this guideline important and how will it change practice? SPEAKER 3: Thank you. Well, as Dr. Mohile said at the start, it is quite challenging to review the literature for gliomas in adults because we've had different nomenclature applied across clinical trials and diagnostic studies over the last 10 to 15 years. And this document and these guidelines really seek to be the clearinghouse to help clinicians match up what they see on the pathology report for their patient to the data that is published on phase III studies that has influenced our current standards of care. So I think the most important way it will change practice is bringing clarity to the data that already exists but has not been accessible to providers trying to help patients make the best decisions for them. It also importantly highlighted how much more work is needed. We desperately need new clinical trials for patients with glioblastoma and patients with astrocytoma IDH wild type 1p19q non-co-deleted WHO grade 2 and 3 and the other areas that Dr. Mohile highlighted. But we're hopeful that this will help provide clarity on both what we do know to help us identify patients who have the best chance of truly meaningful benefit from chemotherapy and where we need to invest more resources. SPEAKER 2: Absolutely. It seems like this will be a helpful resource for how to treat now and a guide as to what areas of research should be investigated in the future. So in addition to that, Dr. Mohile, finally, how do you view that these guideline recommendations will impact patients? SPEAKER 4: Yeah, my hope is that this will help standardize our approach to patients with gliomas. In the United States, patients with gliomas get care in all kinds of different settings. And when they're seeing an oncologist, particularly in the community, this might be a very small percentage of the types of cancers that they might be seeing, and it's hard to keep up with all of these trials and hard to keep up with the changes in classification. So our hope is that this guideline helps that oncologist in providing them the clarity, as Dr. Blakeley said, on how to approach treatment here so that all of our patients are getting the best standard of care based on the best available evidence and that they're being considered in those areas where there is not good evidence or referral for clinical trials so that in 10 years, when we put together the next guideline, that we're able to make some progress on some of these questions. SPEAKER 2: Great. Well, thank you both for all of your work that you did to review the literature and produce these evidence-based recommendations and, as you said, provide a real clear and helpful resource to both clinicians and to improve the quality of care for patients. And thank you for taking the time to speak with me today, Dr. Mohile and Dr. Blakeley. Finally, thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/neurooncology guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

ISMP Targeted Medication Safety Best Practices for Hospitals #1 is to dispense vinCRIStine and other vinca alkaloids in a minibag of a compatible solution and not in a syringe. This best practice is to prevent intrathecal infusion, which can be lethal. Learn how one health system implemented this best practice. The information presented during the podcast reflects solely the opinions of the presenter. The information and materials are not, and are not intended as, a comprehensive source of drug information on this topic. The contents of the podcast have not been reviewed by ASHP, and should neither be interpreted as the official policies of ASHP, nor an endorsement of any product(s), nor should they be considered as a substitute for the professional judgment of the pharmacist or physician.

This episode covers vincristine and vinblastine!

A lot can happen in two years. You might have matched into residency, graduated from fellowship, had a kid... Or several phase II trials in low grade glioma research could have been published. Since the original airing of this episode in May 2018, there have been a few updates in neuro-oncology. We'll cover some of the major ones this week in the BrainWaves podcast. Produced by James E. Siegler, Brian Nahed and Jorg Dietrich. Music courtesy of Ian Sutherland, Lovira, and Lee Roosevere. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast. REFERENCES McGirt MJ, Chaichana KL, Attenello FJ, Weingart JD, Than K, Burger PC, Olivi A, Brem H and Quinones-Hinojosa A. Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery. 2008;63:700-7; author reply 707-8. Shaw EG, Wang M, Coons SW, Brachman DG, Buckner JC, Stelzer KJ, Barger GR, Brown PD, Gilbert MR and Mehta MP. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30:3065-70. Schiff D. Low-grade Gliomas. Continuum (Minneap Minn). 2017;23:1564-1579. Wen PY and Huse JT. 2016 World Health Organization Classification of Central Nervous System Tumors. Continuum (Minneap Minn). 2017;23:1531-1547. Bell EH, Zhang P, Fisher BJ, Macdonald DR, McElroy JP, Lesser GJ, Fleming J, Chakraborty AR, Liu Z, Becker AP, Fabian D, Aldape KD, Ashby LS, Werner-Wasik M, Walker EM, Bahary JP, Kwok Y, Yu HM, Laack NN, Schultz CJ, Gray HJ, Robins HI, Mehta MP and Chakravarti A. Association of MGMT Promoter Methylation Status With Survival Outcomes in Patients With High-Risk Glioma Treated With Radiotherapy and Temozolomide: An Analysis From the NRG Oncology/RTOG 0424 Trial. JAMA Oncol. 2018;4:1405-1409. van den Bent MJ, Klein M, Smits M, Reijneveld JC, French PJ, Clement P, de Vos FYF, Wick A, Mulholland PJ, Taphoorn MJB, Lewis J, Weller M, Chinot OL, Kros JM, de Heer I, Verschuere T, Coens C, Golfinopoulos V, Gorlia T and Idbaih A. Bevacizumab and temozolomide in patients with first recurrence of WHO grade II and III glioma, without 1p/19q co-deletion (TAVAREC): a randomised controlled phase 2 EORTC trial. Lancet Oncol. 2018;19:1170-1179. Fangusaro J, Onar-Thomas A, Young Poussaint T, Wu S, Ligon AH, Lindeman N, Banerjee A, Packer RJ, Kilburn LB, Goldman S, Pollack IF, Qaddoumi I, Jakacki RI, Fisher PG, Dhall G, Baxter P, Kreissman SG, Stewart CF, Jones DTW, Pfister SM, Vezina G, Stern JS, Panigrahy A, Patay Z, Tamrazi B, Jones JY, Haque SS, Enterline DS, Cha S, Fisher MJ, Doyle LA, Smith M, Dunkel IJ and Fouladi M. Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol. 2019;20:1011-1022. Bell EH, Zhang P, Shaw EG, Buckner JC, Barger GR, Bullard DE, Mehta MP, Gilbert MR, Brown PD, Stelzer KJ, McElroy JP, Fleming JL, Timmers CD, Becker AP, Salavaggione AL, Liu Z, Aldape K, Brachman DG, Gertler SZ, Murtha AD, Schultz CJ, Johnson D, Laack NN, Hunter GK, Crocker IR, Won M and Chakravarti A. Comprehensive Genomic Analysis in NRG Oncology/RTOG 9802: A Phase III Trial of Radiation Versus Radiation Plus Procarbazine, Lomustine (CCNU), and Vincristine in High-Risk Low-Grade Glioma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020:JCO1902983. Breen WG, Anderson SK, Carrero XW, Brown PD, Ballman KV, O'Neill BP, Curran WJ, Abrams RA, Laack NN, Levitt R, Galanis E, Buckner JC and Shaw EG. Final report from Intergroup NCCTG 86-72-51 (Alliance): a phase III randomized clinical trial of high-dose versus low-dose radiation for adult low-grade glioma. Neuro Oncol. 2020;22:830-837. Ullrich NJ, Prabhu SP, Reddy AT, Fisher MJ, Packer R, Goldman S, Robison NJ, Gutmann DH, Viskochil DH, Allen JC, Korf B, Cantor A, Cutter G, Thomas C, Perentesis JP, Mizuno T, Vinks AA, Manley PE, Chi SN, Kieran MW and Consortium NFCT. A Phase II Study of Continuous Oral mTOR Inhibitor Everolimus for Recurrent, Radiographic-Progressive Neurofibromatosis Type 1-Associated Pediatric Low-Grade Glioma: A Neurofibromatosis Clinical Trials Consortium Study. Neuro Oncol. 2020.

Mississippi Edition for Monday, October 21:Find out how a nationwide shortage of an anti-cancer drug is affecting kids with cancer right here in Mississippi. And after Byte Size Tech, the family of the late Emmett Till is in Mississippi to honor the Chicago teen whose Delta murder was a catalyst in the civil rights movement. And find out how digital technology is giving people a way to remember Till that can never be riddled with bullets. ____________________________________Segment 1:A nationwide shortage of a critical pediatric cancer drug has Mississippi's Batson Children's Hospital putting a contingency plan in place. Dr. Anderson Collier says one of the two companies that made Vincristine has stopped production. He says doctors use the drug for almost every major tumor they treat in children. Through careful rationing, Collier says they should have enough Vincristine to get through six weeks or so. After that, who knows? Dr. Anderson Collier spoke with MPB's Desare Frazier.____________________________________Segment 2: Byte Size Tech ____________________________________Segment 3: A fourth sign commemorating Emmett Till's death is now up in the Mississippi Delta near the site where the Chicago teen was found murdered in 1955. The new sign replaces the bullet-riddled sign which was only put up last year. This summer, an image of three University of Mississippi students standing near the vandalized sign with guns went viral. The Emmett Till Memory Project mobile app is on APPLE and GOOGLE. See acast.com/privacy for privacy and opt-out information.

Dr. Hayes interviews Dr. Freireich on his involvement with combination chemotherapy.   TRANSCRIPT: 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Welcome to JCO's Cancer Stories, the Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. Welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm a medical oncologist and a translational researcher at the University of Michigan Rogel Cancer Center. And I've also had the privilege of being the past president of the American Society of Clinical Oncology. I'm privileged to be your host for a series of podcast interviews with the people who founded our field. Over the last 40 years, I've been fortunate to have been trained, mentored, and also, frankly, inspired by these pioneers. In fact, it's my hope that, through these conversations, we can all be equally inspired by gaining an appreciation of the courage, the vision, and the scientific understanding that led these men and women to establish the field of clinical cancer care over the last 70 years. In fact, by understanding how we got to the present and what we now consider normal in oncology, we can also imagine, and we can work together towards a better future for our patients and their families during and after cancer treatment. Today, my guest on this podcast is Dr. Emil J. Freireich, who is generally considered one of the pioneers of combination chemotherapy. Dr. Freireich is currently the Ruth Harriet Haynesworth chair and distinguished teaching professor in the Department of Leukemia at the Division of Cancer Medicine at MD Anderson Cancer Center in Houston. He was raised in Chicago during the Great Depression, the son of Hungarian immigrants. Dr. Freireich attended the University of Illinois College of Medicine in Chicago starting, unbelievably, at age 16. And from there, he also received a medical degree in 1949. He completed his internship at Cook County Hospital and his residency at Presbyterian Hospital in Chicago. He then moved to Boston, where he studied hematology with Dr. Joseph Ross at Mass. General. And then he went to the NIH in 1955, where he stayed until he moved to MD Anderson a decade later. And there he still remains. He and his colleagues at the National Cancer Institute, Drs. Jim Holland and Emil "Tom" Frei, were the first to demonstrate that administering concurrent combination chemotherapy, rather than giving it sequentially with each episode of disease progression, resulted in complete responses in childhood acute lymphocytic leukemia. And that paper was first published in the now classic paper in Blood in 1958. In the mid-1960s, they ultimately developed the VAMP regimen. And that was reported in 1965, with really, in my opinion, the first cures that we'd seen with chemotherapy in an advanced cancer of any sort. This work was the groundbreaking basis for the subsequent cures of advanced Hodgkin's disease, non-Hodgkin's lymphomas, adult leukemias, testicular cancer, and, in my opinion, the striking results of adjuvant combination chemotherapy in breast and many other cancers. Dr. Freireich has authored over 500 peer-reviewed papers, numerous reviews and editorials. He's edited 16 different textbooks. And he's won too many awards and honors for me to even begin to list. But in particular in 1972, he received the Lasker Award, America's most highly regarded medical honor. And most importantly to me, frankly, is that he proceeded me as president of ASCO in 1980 to 1981. Dr. Freireich, I'm sorry for the long introduction. But your career is pretty substantial. Welcome to our program. Thank you. I have a number of questions. And to start with, I know, as I said, you grew up in Chicago during the depression and that you entered college at the age of 16. And I think our listeners would love to hear more about those circumstances. That's pretty unusual. And I've actually read about some of your childhood. You want to tell us more about that and how was it you chose medicine in the first place? I was born 1927 of to immigrant Hungarians. I had an older sister three years older. And they had a Hungarian restaurant in Chicago. And 1929, when I was two years old, there was a big event in the United States. They lost their restaurant. My father died suddenly, I believe of suicide, but not proven. And my mother, tough mother, went to work in a sweatshop. She worked 20 hours a day. She had two children. She found an Irish lady who worked for room and board only, no salary. Her name was Mary. So Mary was my ex officio mother. And I grew up, as you pointed out, in a ghetto community. I spent my life stealing things, hubcaps and windshield wipers, and avoiding getting crushed by the roving gangs. When I finished elementary school and when I went to a ghetto high school called Tuley, T-U-L-E-Y. In Tuley High School, I majored in typing and shorthand. My mother thought I could make a living as a secretary. I was prepubescent, short and fat. And I was a frequent victim of my colleagues in school. When I was very young, I can't tell you when, about eight or so, I developed tonsillitis. And we had in our little ghetto community one of these Tree Grows in Brooklyn physicians. His name was Dr. Rosenblum. And he took care of people in the ghetto for favors. My mother made him goulash. Dr. Rosenblum came to your house. He didn't have an office, because we didn't have any transportation. So my mother called him. And I had tonsillitis. He came and looked to me. He was wearing a suit and tie. I'd never seen that. During the depression, all the men wore coveralls and dirty pants. And he looks very elegant. He had a suit and a tie. He looked in my throat, and he said to my mother, the treatment for tonsillitis is ice cream. I always remember Dr. Rosenblum, because my mother had to go out and buy ice scream. And it's not bad treatment. It actually cools off the hot throat. So when I went to high school, taking shorthand and typing and getting beaten up by the bigger guys, a professor appeared like Dr. Rosenblum, suit and tie, young guy, PhD. Came to a ghetto high school to teach physics. Physics fascinated me. So I worked very hard in physics. He had a contest. I did a project on the Bernoulli theorem. And the classic project is a jet of water. You put a ping pong ball in it. And the ping pong ball stays in the jet, amazingly. That was because of Bernoulli. What happens when the ping pong ball goes off to one side, the fluid goes faster on the other side. It reduces the pressure, and that pushes it back in the stream. And that's the principle of airplanes and so on and so forth. So I won first prize. And he called me to his office. He said, Mr. Freireich, you should go to college. I said, what's college? He said, well, there's-- [LAUGHTER] He said there's a place down south of here called the University of Illinois where you can get advanced studies. What do you want to be when you grow up? So I thought a minute, and I said, I want to be like Dr. Rosenblum. I want to be a family doctor. He said, well, you have to go to college first. So I said, what do I need to go to college? He said you need about $25, which in that day was a lot of money. So I went home, and I told if it was my mother, my professor wants me to go to college. And I need $25. My mother, she's hardened in the depression, working in sweatshops. And she said, OK, I'm going to get $25. She asked around in the little Hungarian ghetto community. And we found a lady who had lost her husband and had an insurance policy. And so she had money. And she distributed it to her colleagues in the ghetto community for good causes, wonderful lady. So my mother dressed me up in a borrowed suit. And we went to see Mrs. so-and-so. And she patted my head and gave my mother $25. It's an incredible story. In fact, I'm struck by the fact that one of the founders of our field was a juvenile delinquent stealing hubcaps. Oh, yeah. I did that to hubcaps and windshield wipers and everything you could take off a car. I got a ticket on the Illinois Central Railroad, $6. I got off the Champaign-Urbana. And I said to the guy, where's the university? He said, over there. I went over there. I said, where do you register. They said, over there. So I went over there. And I said, I'm Freireich, and I'm registering for college. The guy said, where's your transcript. I said, well, they told me at the high school that they would send everything they needed. He said, we've never had a student from Tuley High School. I was the first to go. I was the first Tuley student to go to college. And he said, OK, I'll register you. And I'll write the university, and I'll get your transcript. I presume you're qualified. So how much is registration? $6! So I'm down to $13. I'm getting pretty poor. So I registered. And then I said, where do I live? He said, there's a list over there. And I went over there. I found the lady who lost her husband. She rented his bedroom for $6. And then I had to figure out how to eat. And I asked my friend the registrar, where do I eat? He said, go to work in one of these rich sorority houses. You get free meals. So I waited tables in a sorority house. I got good grades. When I had to elect a language, I took German, because at that time, all the science was in the Festschrift. The Germans had invented the chemical industry. And my advisor said, that's good for you if you want to be a doctor. So I took German. My professor in German, he taught stage German. And he read the role the first day. And he came to my name and he said Freireich, [EXAGGERATING "CH" SOUND] because, he said, Americans can't say. [EXAGGERATED "CH" SOUND] Everybody called me "Freireish." But he called me Freireich [EXAGGERATING "CH" SOUND]. And our book was called, Ich lerne Deutsch, I'm learning German. So "ich" was important. Freireich was important. I got an A in German because of my great name. And I did well in physics. And everything was accelerated during the war. So the university had three semesters a year instead of two. There was no summer. And the requirements for medical school were dropped from three years to two years. So two years is four semesters. So at the end of the first year, I was eligible for medical school. And my physics professor said, you better apply, because all the guys coming out of the military want to be doctors. So I said, aw, damn, I'm having such a good time scrubbing floors and smoking and getting along with good looking girls. He said, you better do it. So I applied. And I was accepted. So I had to leave the beautiful campus of Champaign-Urbana and go back to the ghetto of Chicago where my mother and my sister were living. And I couldn't figure out where I was going to get the money to pay for medical school. I had a friend who had had polio. Polio was rampant in those days. And I said to him, how do you get money to go to college? He said he gets money from the state, rehabilitation. And he said my rehab guy is coming to see me tomorrow. Why don't you come and see if you're eligible? So the rehab guy came. He said, what's wrong with you, Freireich? I said, I had a broken leg in college. He said, OK, fill in the forms. And I became a ward of the state of Illinois Department of Rehabilitation. From that point on, they paid all my tuition, all my supplies, all my microscope rentals, and so on. So I went to medical school free thanks to the State of Illinois Department of rehabilitation. So I went to Chicago. And a bunch of us sat in the room for the opening introduction. And the dean of the medical school came in. His name was Andrew C Ivey. I don't know if you know the name, famous GI physiologist. And Dr. Ivey said, you guys are lucky to be in medical school. There were 20 applicants for everyone accepted, 20. Isn't that's amazing? Because all the guys who were medics in the military realized that being a doctor is a soft job. So they all wanted to be doctors. But they didn't have as good an academic career as I did. So anyhow, I went to medical school. I did pretty well. It was complicated, medical school. I had to ride the L in Chicago. It cost a nickel. And I lived at home. And I rode the L in the morning. And I walked to the university campus. I attended classes. I walked to the L. And I went back home. And I did that for four years. And then, as I said, I graduated number six in the class. And I graduated. And I had to decide where to do an intern. I wanted to be a family doctor like Dr. Rosenblum. So I interned at Cook County Hospital. Cook County Hospital was an abattoir, terrible place. In that year, 1949, the two most prominent diseases were tuberculosis and polio. So my first rotation was the TB ward. That was horrible what you had to do to those men. 90% of them died. Then my next rotation was infectious diseases. And that was all children in iron lungs who were doomed to die. So I started off pretty badly. And then I got to the good things like surgery. I delivered a hundred babies. I did the ear, nose and throat. So I did everything. And I felt ready to go into practice. And then I got to internal medicine. Internal medicine was not like OB and all that stuff, not mechanical. It was intellectual. You had the worry about the blood flow to the kidney. And you had to get diuretics and blood and stuff. So internal medicine fascinated me. When I was on-call, I would admit 20 new patients a night, 20. And one guy I admitted was very interesting. He was a learned guy. And he was dying of heart failure. And I had to figure out how to treat him. And I admitted him. And when I got done, exhausted in the morning, I went to make rounds. And I didn't see him. And I said to the nurse, where's Mr. so-and-so. She said, don't worry about him. He's gone. I said, where did he go. She said he goes into the death room. Cook County Hospital, the problem was they had too many patients for the beds. And the head nurse made rounds every day. And the sickest patients went to the death room. And I went in there. And I found my patient. And I said to the nurse, I want my patient on the ward. I'm a young squirt. How old was I? I was 19, I think. So the next day, I get a call from the hospital director. He says, Freireich, I think you better leave County. I said, what do you mean? I'm having a good time. I'm learning everything. He said, you don't know how we operate. The nurses run the ward. And you make trouble. And that means you've got to leave. Uh-oh. So I said, well, the only thing I can do is get a residency in medicine and learn all this complicated stuff. So next door was Presbyterian Hospital, which had the Rush Clinic. Have you heard the rush clinic? They were a bunch of famous guys. I made rounds with Roland Woodyatt, the first physician in the United States to use insulin. I made rounds with-- I forgot the name of the cardiologist who described coronary artery disease. He was the first to recognize the association between chest pain and myocardial infarction. So these guys were great. And Olie Poll, who taught me EKG-- And I was going along fine. But again, the chair of medicine was a Harvard import, S Howard Armstrong. And he had a teaching service. And all the house staff wanted to be on the teaching service where they learned stuff. Private doctors, of course, were offended. So they descended on administration. And they fired the chair of medicine. Armstrong was fired. The house staff teaching service was disbanded. And Armstrong tried to tend to his house. He called me in. He said, Freireich, what do you know about medicine? I said, Dr. Armstrong, you got a wonderful department. I learned EKG. I learned diabetes. I learned heart. I learned everything. The only thing I don't know anything about is hematology, because the guy who teaches hematology is a jerk. Armstrong said, don't worry, Freireich. Go to Boston, that's where the new medicine is coming from Europe. And he gave me letters to the three great hematologists in Boston, Bill Dameshek, Joe Ross, and Dr. Israel, who was a clotter. So I took everything I owned. I put it in my 1946 fastback, broken down Oldsmobile. And I drove to Boston. When I got to Boston, I met Dr. Ross. The guy in the lab who was the chief was so Stuart Finch. I think he just retired. And I collaborated with a young man named Aaron Miller who worked at the VA hospital. And my project funded. Dameshek gave me a job but no money. Israel gave me a job, no money. Ross gave me a job and paid me $5,000 a year, wonderful. So I became a hematologist. I worked on the mechanism of the anemia of inflammation. I studied patients with rheumatoid arthritis. And we had radioisotopes. So I was able to study the iron metabolism and the binding to transferrant. And we did experiments in dogs. And we worked out the mechanism of the anemia. The biggest hematology group in the country, the Wintrobe group, who wrote the textbook, had proven that the anemia of inflammation was due to a failure to incorporate iron into heme. And we found that that was false. When we put the ion on transferrant, it went right into heme. The difficulty was the reutilization of iron from hemoglobin to new heme. And we proved that in dogs. We did experiments with turpentine abcesses in dogs. So I was on a roll. I was doing Nobel laureate stuff. I mean, I gave a paper to the AAP. I gave a paper to the ASCI. I was doing well. And one day I got a letter. You are drafted into the army as a private. If you don't want to be a private, you can become a second lieutenant if you accept the assignment we give you. So I told Ross, I'm leaving. I got to go. I tried to finish up all my experiments. I told my wife we're in trouble. We didn't know what we'd do. We had one baby, one-year-old. She was pregnant with our second child. I didn't tell you the story about my wife. What happened is the head nurse in the clinic, like me, she came for a visit to Boston. They broke into my car and stole her luggage. And so we became attached. And we got married. And we've been married 65 years. But anyhow, she got a job at Mass. General. I had a job at Mass. Memorial. We had enough money to live. And as I say, she got pregnant, and we had babies. And I got this letter that I'm drafted. So I said to my wife, we have to go to the Army. The next morning, I get a call from Chester Scott. Keefer, who you already mentioned-- Dr. Keefer was the physician in charge of the penicillin distribution during the war. He was a very famous infectious disease doctor. He was a brilliant teacher and respected and loved by everybody. When Eisenhower was elected president, as you probably know, like all Republicans, he wanted to decrease the size of the government. So he decided to combine three cabinet departments, Health, Education, and Welfare, into one. That was obviously going to save positions and money. And he appointed Oveta Culp Hobby, who was the publisher of the Houston Post newspaper. She didn't know anything about health. She didn't know anything about education or anything about welfare. So what she did was she hired three people as department heads. And she picked Dr. Keefer to be head of health. Dr. Keefer would not give up the dean of the medical school. So she agreed to have him do both jobs. He was dean of the medical school and Secretary of Health. And he called me to his office. And we all respected Dr. Keefer. You dressed up in a new coat and clicked your heels and said, yes, sir. He said, Freireich, Dr. Ross says you're doing good. Thank you, sir. Have you ever heard of the National Institutes of Health? No, sir. There's a place in Washington where they have a hospital out in the country. And they can't staff it. So we have to send young people who are drafted there. If you go to the public health service, you don't have to go in the army and get shot during the war. Yes, sir. He picked up the phone. Fred, I have a doctor Freireich in my office. He'll be there tomorrow morning. Bye. Thank you. I went home. I told my wife, I have to go to Washington. I got in my car, drove to Washington, 200 miles in a broken down car. I got there. I found the guy at the HEW. He said, Freireich, you have to go to NIH. So go out here and take the bus. It takes you to the clinical center. Before the war, they decided to put a clinical center in the campus of the National Institutes of Health, which were all basic science institutes. There was no medicine. So here was this hospital, and they couldn't staff it. So they took all the draft dodgers. They called us yellow berets. And they staff the NIH with guys right out of their training. So anyhow, I got in my car and drove out there. Where's NIH? There. Who do I talk to? There, you go there. I talked to all the clinical directors. No one needed me. I got to Gordon Zubrod, who had just come from St. Louis University. He was an infectious disease guy. Do you know Gordon Zubrod? Yeah, I actually met him a couple of times with Dr. Frei. Good, yes. Actually, I'd love to hear this story. Dr. Frei has told me the story, your first day at the NCI when you, quote, "found your office." Can you tell us about that one? Yeah. So anyhow, Dr. Zubrod said, what do you do, Freireich? I said, I'm a hematologist. He scratched his head. And he said, I'll tell you what, you have to cure leukemia. I said, yes, sir. You know I'm in the military, so you have to do what you're told. He said, your office is on the 12th floor. I went up to the the 12th floor. I walked along, looked for a name. I came to room that said Emil Frei. I said, isn't that like the damn government? They can't even spell my name. So I walked in. And there was a tall, skinny guy with no hair. I said, sir, you're in my office. He said, your office is next door. I'm Frei. You're Freireich. And we've been friends for a lifetime. He told that story to us many, many times, I'm going to tell you. He thought that was hilarious that this guy walked into his office and said, you're in my office. And he said, no, you're in my office. The other thing I want to talk about then, as you moved on, what made you and Dr. Frei and Dr. Holland decide to go at combination therapy? I think it was based on the infectious disease stuff. Correct, totally. At the time, we had three drugs, 6-MP, methotrexate, prednisone, 48, 53, and about 54, something. Each individually gave some responses. They lasted six to eight weeks. And the children all died. So the world's authority on hematology, Max Wintrobe, wrote a review. And he said, these drugs are simply torturing these children. And they don't do anything. Dameshek wrote editorials in Blood saying they're just killing children. So we were not very popular. But Zubrod came from infectious disease. And Tom Frei was infectious disease. And they had just discovered that in tuberculosis, if you use sequential streptomycin PAS, they became resistant to both drugs. If you gave them simultaneously, their effectiveness was prolonged. So combinations of agents were more effective than the sequences. So Zubrod said, why don't we do the same thing for cancer? We'll do 6-MP and methotrexate in sequence. And we'll do them in combination. To do the combination, we had to work out the doses. Dave Rolle did that in mice. 60% of two immunosuppressive drugs make one. And we gave 6-MP and methotrexate concurrently and in full dose sequentially, that is until they failed, we gave the other one. And the study was called Protocol 1. Jim Holland had gone to Roswell Park. And he agreed to join us. So we became the first acute leukemia cooperative group, Holland at Roswell Park, Frei and Freireich at MD Anderson. Freireich treated the children. And Frei protected Freireich from the rest at NCI and from Zubrod. Zubrod trusted Frei. So if I needed to do anything radical, I'd talk to Frei, and he'd talk to Zubrod. So we were a great team. That was really the start of the cooperative group set, right? That would be CALG, the cancer and leukemia group, is that right? That was the first cooperative group in the country. That's incredible. The cooperative group had to two institutions, Roswell Park and MD Anderson. Who tried to block you on these things? I know it must have taken a lot of courage to put all these drugs together. You mentioned Wintrobe. But were there others who were fundamentally opposed to using combinations? Oh, I'm getting to that. So with the first study, Protocol 1, Russell Park and MD Anderson, children received 6-MP and methotrexate simultaneously and in sequence. And it turned out that Protocol 1 was published. The combination had more frequent remissions and longer duration. So we were onto something. Next we did the prednisone. Prednisone's not myelosuppressive. We could do full-dose prednisone with 6-MP, full dose prednisone with methotrexate, same result. In every instance, the combination was superior to the sequence. So one day I'm sitting in my office. About once a week he'd come around and look. He came in one day. He said, Dr. Freireich, this ward is a mess. Everything is full of blood, the nurse's uniforms, the curtains, the ceiling. Well, anyhow, I was taking care of my bleeding children one day when a guy from Eli Lilly showed up. I think his name was Armstrong. And he said, we've got a new drug that was founded by-- you know who that was. Let me see his name. Mike Black. He discovered it in mice, periwinkle extract. Periwinkle had 80 alkaloids. And they screened them all against mice. And this one was active in one kind of mouse leukemia. But it wasn't active in L1210. So he said, we have this drug. And we offered it to Dr. Farber at Dana Farber. And we're going to offer it to you if you want to do it. I said, wonderful. So I wrote a protocol. And Zubrod said, but this drug is not active in L1210. And we know that the drugs active in L12101 leukemia are active in human leukemia. So this drug cannot be studied. Aha, time for Emil Frei III. I went to Tom. I said, look, Tom, vincristine is not myelosuppressive. As a single agent, it causes 80% complete remissions. I want to vincristine to 6-MP and methotrexate. Zubrod says no. Frei said, leave it to me. He talked to Zubrod. I told Zubrod, these children are dying. I've got to do something. So they approved it. And we did decide the VAMP. We knew prednisone was not myelosuppressive. We could add it to 6-MP and methotrexate, full dose. We knew this dose of 6-MP and methotrexate. Vincristine turned out to be not myelosuppressive, CNS toxicity. So we designed the VAMP drug. Then we said, let's let Holland and the other members of the cooperative group join so we can get this done quick. The cooperative group refused. Jim Holland refused. He wanted to do them one at a time, prednisone, 6-MP, methotrexate, vincristine, prednisone, vincristine, and so on. It would have taken us five years. We went through the same thing with MOPP. They wanted to do it one at a time. So we had to do it alone in the cancer institute. So Frei went to Zubrod and said, why can't we do it? Zubrod said, if you say it's OK, you can do it. Frei was chair of the group. And I'm not going to put my patients on the group. So Frei had to resign. Holland became the chair. And Frei was an advisor. So we started out with VAMP. We had 98% remissions. The remissions lasted about six weeks. We realized that they weren't cured. So we said to the parents, this treatment was toxic. It was full-dose 6-MP and methotrexate. And the parents said they're going to risk their children's life, but we're going to do what we called early intensification. That is, the children in complete remission would get full-dose induction therapy, never done before. And I met with the parents every morning and went over each child to be sure that they were with us. The parents were wonderful. We had solved the bleeding problem with platelet transfusions. We'd had white cell transfusions and so on. And they went along with us. So we did early intensification. We did it in about 12 patients. Two of them almost died, very severe infection on the brain. But we saved them. So we knew this was dangerous. But they all relapsed. Median duration remission was about eight weeks, even though we did early intensification. So MC Li had cured choriocarcinoma. I don't know if you know that story. MC Li and I were residents at Presbyterian at the same time. We were good friends. I was his advisor on this strategy. He measured chorionic gonadotropin in the urine. And he knew that as long as there was gonadotropin in the urine, they weren't cured. So he kept treating them. So we decided to follow the Li model. And what we did was we did early intensification, which they all survived, fortunately. And then we did intermittent reinduction. Every four to six weeks, we'd bring them in and give them another course of treatment. And we did that for a year. And then we stopped. And then we watched them. And that's when we found 20% of the patients were in remission at, I think, 18 months. Never been reported before. And I did report that to AACR. I've seen the AACR abstract. And I would love to know what was the energy in the room when that was presented. Did people stand up and throw rotten tomatoes at you, or did they stand up and applaud, or everything in between? No one applauded. Everybody was incredulous. The people in the group didn't believe it. Most people thought we were lying. If it wasn't for Frei, I'd have never gotten away with it. Let me ask you another question. Dr. Frei told me that the first patient you gave platelets to, you had to sneak out at night and do it. Is that true? He said there were people who did not want you to give platelet transfusions. The platelet transfusions were a bigger fight than the chemotherapy, because everybody knew that platelets were not the cause of it. Dr. Brecher had studied patients in the war from radiation injury. He had dogs that he completely phoresed, zero platelets. And they didn't bleed. So obviously, platelets were not the problem. The problem was a circulating anticoagulant. And I did experiments in the lab and proved that that was false. But anyway, the platelet transfusions are what made all of this possible, because the children all died of hemorrhage. And once we had platelets, we could treat them with the chemotherapy. Is there a story behind the first patients who got platelet transfusions? Again, Dr. Frei told me that-- Oh, boy, that's a wonderful story. I actually published it. This was a young man who was bleeding to death whose father was a minister. And since it was proven that platelets were not important and there was a circulating anticoagulant, I decided that the only way to arrest the hemorrhage was to do an exchange transfusion like you do in eritroblastosis fetalis. So I said to the minister, if you bring me 10 healthy volunteers, I want to do this experiment on your son. And he was desperate. His son was a beautiful 8-year-old boy. His name was Scotty Dinsmore. How do you like that? [LAUGHTER] Scotty Dinsmore was bleeding to death. And he arrived the next morning with 10 volunteers. And I sat down in the treatment room. And I did an exchange transfusion with 50 cc syringes, 50 ccs from Scotty in the trash can, 50 ccs from the donor in Scotty. And we calculated I had exchanged three blood volumes to get to where the concentration was detectable. And when I finished this four-hour procedure, bending over my back with syringes and volunteers, his platelet count was 100,000. And is bleeding completely stopped. So we thought we'd made a breakthrough, but we were smarter than that. We watched him every day and did a platelet count. And we found that the platelet lifespan was four to six days. And when the platelets got below 10,000-- we had done a retrospective study, and we knew what the threshold for bleeding was. And he started bleeding again. So it was obvious that it was not an anticoagulant. I did experiments in my lab. I took the serum and mixed it with the plasma and so forth. So we proved that it was platelets and not an anticoagulant. And then we had to figure out how to get platelets. And Allen Kleiman in the blood bank and I worked together to do platelet phoresis. We took the unit separate platelets, put the blood back, volunteer donors. And we proved that platelets stopped the bleeding. And we published that, a great paper, citation classic. I was going to say for the young folks. And I asked Dr. Frei this too when I was at the Dana Farber. Did you ever doubt yourself? Did you think, we need to quit doing this? This is more than we can handle. I know Dr. Farber was widely criticized in Boston for-- Oh, boy. He studied vincristine at the same time we did. Yeah. So did you ever say, maybe we should set this whole system down and give up? No, I was never intimidated, because Dr. Zubrod gave me orders, cure leukemia. So I was going to do it. Yeah, my impression from talking with Dr. Frei is Gordon Zubrod was the sort of unsung hero in all of this. He is. He is. He had the courage to back a 25-year-old guy and his resident to do things that were potentially insane. We could have gone to jail for what we did. We could have killed all those kids. That's what Dr. Frei-- Dr. Holland has told me the same story. So we owe you a great debt. So let me ask you. When you were the president of ASCO, in those days, what made you decide to run for ASCO? It was still pretty early in the early 1980s. Well, that's a very good story. I'm a pioneer in that regard too. When you became a cancer doctor, you had to join the AACR. AACR was dominant. I joined the AACR. I sent my papers on platelets and chemotherapy to AACR. They accepted all of them. But they put the clinical papers on Saturday morning. When I gave my first paper at AACR, the chairman of the session, my wife and my son were the only ones in the audience. Nobody stayed till Saturday morning. So I got mad. I said, I'm discovering things, and I can't present them at AACR. No one's listening. So we said, let's form a society that is clinical oncology and meets the day before AACR the clinical scientists who want to go AACR don't have to go to two meetings. So we organized a plenary meeting the day before AACR began. In the first session, we had a lecture on CML from-- I forgot who the talker was who is treating CML, Berechenal or someone. Karanovsky? I don't know. So we had lectures, not papers. And we did that for a couple of years. And then AACR knew what we were doing. We were totally cooperating. But we hired a manager. And we started a scientific exhibit. So we had lots of money. And AACR needed money. And we were rich. So I got a call from the president of AACR. And he said, we don't want to continue to meet at the same time, because all of our doctors want to get these free samples. And they go to your meetings, and they don't go to our meetings. So we're separating from ASCO. I said, that's terrible, because the ASCO doctors all want to go AACR. He said, sorry, we can't take you anymore. I forgot who was president at the time. So ASCO had to separate from AACR. They separated from us. Most people think we separated from them. They separated from us. You were there at the very start. So I really appreciate your contributions to the field. And I appreciate your taking time today. And I appreciate all the things you did to help all the patients who've now survived that wouldn't have if you hadn't. Thank you very much. Until next time, thank you for listening to this JCO's Cancer Stories, the Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple podcast or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories, the Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org.

Kat Arney unearths the story of a truly international effort to develop new drugs for cancer, and the female researcher whose key role went overlooked

De Wakkere Wetenschapper van deze week is Mirjam van de Velde. Zij doet in Memphis onderzoek naar de bijwerkingen van het medicijn Vincristine. Vincristine wordt gebruikt bij de behandeling van veel verschillende soorten van kinderkanker.

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.    

The Foundations in Oncology Pharmacy continues with vincristine. Its origin, unique toxicity profile, and clinical use is discussed. Periwinkle!

In today's VETgirl online veterinary continuing education podcast, we discuss treatment for immune-mediated thrombocytopenia (ITP) in dogs. Have you treated a patient with primary ITP? Did you use steroids alone, or did you try combination therapy with vincristine or human intravenous immunoglobulin (hIVIG)? Well, while treatment with immunosuppressive doses of glucocorticoids is the initial treatment of choice, and most patients will have platelet recovery within 1-15 days of starting treatment, adding treatment with vincristine or hIVIG has been shown to shorten platelet recovery time. In some peer-reviewed, scientific veterinary prospective studies, dogs with severe ITP treated with prednisone alone versus prednisone and vincristine, or prednisone alone versus prednisone and hIVIG, both combination therapies resulted in faster increases in platelet numbers and shorter durations of hospitalization. To date, though, there haven't been any studies looking at the efficacy of vincristine versus hIVIG as adjunctive treatments. This is important because hIVIG is much more expensive, and giving it to your patient is more time consuming and challenging that giving vincristine.

In today's VETgirl online veterinary continuing education podcast, we discuss treatment for immune-mediated thrombocytopenia (ITP) in dogs. Have you treated a patient with primary ITP? Did you use steroids alone, or did you try combination therapy with vincristine or human intravenous immunoglobulin (hIVIG)? Well, while treatment with immunosuppressive doses of glucocorticoids is the initial treatment of choice, and most patients will have platelet recovery within 1-15 days of starting treatment, adding treatment with vincristine or hIVIG has been shown to shorten platelet recovery time. In some peer-reviewed, scientific veterinary prospective studies, dogs with severe ITP treated with prednisone alone versus prednisone and vincristine, or prednisone alone versus prednisone and hIVIG, both combination therapies resulted in faster increases in platelet numbers and shorter durations of hospitalization. To date, though, there haven't been any studies looking at the efficacy of vincristine versus hIVIG as adjunctive treatments. This is important because hIVIG is much more expensive, and giving it to your patient is more time consuming and challenging that giving vincristine.

Chelsea Stutchbury took on Katy Perry with BarRat and Jess Buy her single "Vincristine " here > https://goo.gl/pOR2cE < #KatyPerry #Cover #Music

Dr. Cathy Pietanza from Memorial Sloan Kettering Cancer Center discusses standard chemotherapy options for treatment of both sensitive and refractory small cell lung cancer (SCLC).

Dr. Cathy Pietanza from Memorial Sloan Kettering Cancer Center discusses standard chemotherapy options for treatment of both sensitive and refractory small cell lung cancer (SCLC).

Dr. Cathy Pietanza from Memorial Sloan Kettering Cancer Center discusses standard chemotherapy options for treatment of both sensitive and refractory small cell lung cancer (SCLC).

Vincristine is used in a variety of different childhood cancers. This podcast describes its use and side effects.

Interview with William E. Evans, PharmD, author of Association of an Inherited Genetic Variant With Vincristine-Related Peripheral Neuropathy in Children With Acute Lymphoblastic Leukemia

Editor's Audio Summary by Howard Bauchner, MD, Editor in Chief of JAMA, the Journal of the American Medical Association, for the February 24, 2015 issue

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