Podcasts about oxaliplatin

When Joe Bullock began experiencing symptoms of irritable bowel syndrome, he thought he could address it with an over-the-counter medication.  However, when the symptoms persisted, he went in for a colonoscopy.  It revealed an 8cm tumor.  He got it removed and had his colon reattached, but his care team found three cancerous lymph nodes resulting in a diagnosis of Stage 3B colorectal cancer.  Through an aggressive chemotherapy regimen, Joe achieved survivorship.  He now works with Man Up To Cancer, a support group that seeks to help men with the mental aspect of a cancer journey.

Dr. Jon and Brian look at a study (Farkas et al., 2022 https://doi.org/10.1016/j.ibneur.2022.08.007) in mice out of Temple University exploring whether mitragynine can help attenuate chemotherapy-induced peripheral neuropathic (CIPN). The team used oxaliplatin, a chemotherapy drug, to induce this condition in an equal number of male and female mice. Mitragynine was also combined with four … Journal Club #36: Mitragynine for Chemotherapy-Induced Pain Read More » The post Journal Club #36: Mitragynine for Chemotherapy-Induced Pain first appeared on Kratom Science.

L-glutamine is a "conditionally essential" amino acid. What's that? Tune in & find out: what glutamine is, what it does, and when you shouldn't be taking it. Tina & Leah discuss generalities and then delve into specifics, particularly for those who have (or had!) cancer.Glutamine is one of those supplements that many people take…. willy-nilly. That's a bad idea. There is a time and a place for glutamine supplementation. Listen in to find out more.Why is glutamine so tricky to use as a supplement:1-Fact: Glutamine can lessen peripheral neuropathy when taken alongside certain chemo drugs. 2- Fact: Cancers often have a high appetite for glutamine and use it as fuel o grow (proliferate).  As always, Tina & Leah speak from experience and stick to the data. (All while introducing you to oddities like “meat sweats.”)Please like, subscribe/ follow, and leave us a review! If you find this info helpful, please share the show with others you think could benefit.  Or, you can support the show directly with a donation, so we can keep making content and help more people! Support the show

Picture this: it's day 1 of fellowship and your attending needs you to "get consent for treatment." Huh? How do you educate your patient? We share our tips! In this episode, we discuss important considerations, including “does my patient need a port?”, “what if drugs extravasate?”, “how do I keep side effects of drug classes straight?!” *The resources we share are our OWN opinions. Naming of resources are not endorsements. We are not sponsored by any of these entities. Pharmacology 101: * Irritant vs. Vesicant:** Each drug is deemed one of these based on the degree of tissue damage that can result if drug extravasates under skin. 
** Vesicant: needs central access
** Irritant: can be given peripherally 
* Does my patient need a port/picc?** If vesicant; for continuous infusions over several days (e.g. 5-FU); some patients with difficult access may request. 
*Advantages of ports: ** Easy access for labs
** Easy access for chemotherapy/fluids
* Disadvantages: ** Risk of infection
** Risk of thrombosis 
* General overview of chemotherapy side effects: ** Going to target the fastest growing cells in the body, which includes cells that line the GI tract, skin, hair/nails, and blood cells
** Therefore side effects are related: *** GI: nausea/vomiting, diarrhea (sometimes constipation), decreased appetite, taste changes
*** Low blood counts **** WBC nadir ~10-14 days (generally), and recover 21-28 days after chemo
* What about unique side effects of chemotherapy classes? How do we keep them straight?** We love keeping “Chemoman” from the USMLE study days in mind!
* Anthracycline*** MOA: Topoisomerase inhibitors
*** Ends in “rubicin”
*** You might hear people call doxorubicin the “red devil”
*** Used in lots of cancers
*** Hair loss occurs with this one
*** Known to cause cytopenias and associated with higher nausea potential 
*** Unique side effects: **** Heart failure (always get baseline echo!)
**** Development of MDS and leukemia 
* Alkylating agents** MOA: Drugs add alkyl group to the guanine base of the DNA molecule, preventing linking of strands
** End in “fosfamide”
** fosfamide or cyclophosphamide (AKA cytoxan)
** Used in lots of cancers
** Known to cause cytopenias and hair loss
** Unique side effects:*** Secondary MDS or leukemia possible 
*** Ifosfamide = neurotoxicity = methylene blue antidote
*** Cyclophosphamide = hemorrhagic cystitis due to acrolein byproduct accumulation = prevent by giving mesna to protect bladder
* Antimetabolites** MOA: Purine analog, pyrimidine analog, folate antagonists; therefore prevent production of base pairs or binds instead of normal base pairs
** End in “abine” - capecitabine, cytarabine, gemcitabine, cladribine, fludarabine
** Also 5-FU and 6-MP in this category so “number followed by dash”
 ** Unique side effects:*** Think bone marrow suppression in this category 
* Platinum agents** MOA: Believed to cause cross-linking of DNA
** End in “platin”
** Associated with high risk of neuropathy 
** Unique side effects: *** Cisplatin: **** Nephrotoxicity 
**** Ototoxicity 
**** High risk of nausea; need special prophylaxis 
*** Carboplatin: cytopenias
*** Oxaliplatin: higher rates GI side effects 
* Microtubule agents** MOA: Impair microtubule function, therefore impacting cell division
** End in “taxel” or vincristine/vinblastine (“V-stine”)
** Unique side effects: Neuropathy
Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

I am a survivor of stage 3b colorectal cancer. I was diagnosed in May 2018 after a routine colonoscopy. I have been NED since February of 2019. Trevor Maxwell a stage IV CRC patient who created Manuptocancer.com ask me to help him create The Howling Place Group on Facebook. We have grown to 1100 men strong in 16 months. The goal is to help men not to self isolate themselves during cancer diagnosis and treatment. to also support them during survivorshipStage 3b colorectal cancer survivor Durham, N.C.I was diagnosed in May of 2018 with stage3b Colorectal Cancer after a routine Colonoscopy at age 50. I had symptoms for a few months but had ignored them for several months following the death of both my parents in 2017 within a six-month period. During the Colonoscopy, my GI doctor found two polyps and a 1Ocm tumor in my colon. I had surgery to remove the tumor, reconnect my colon, and had 40 lymph nodes removed. Three of those tested positive for cancer. After surgery i underwent treatment with two forms of chemotherapy, Oxaliplatin infusions and Xeloda pills for 8 cycles or six months. In February 2019 I became known as NED (No Evidence of Disease) or cancer-free.Over the last few months, I have been working on finding my voice in the cancer community. I have begun living by the mantra " Cancer might be done with me but I'm not done with cancer." I have looked to other men in the cancer community who have made strides in this area and followed their examples. The following are my current roles of advocacy in the cancer community.*** January 2020 Lead Administrator for the Men's Cancer Facebook support group 'Man Up To Cancer/ The Howling Place' . It's a part of manuptocancer.com *** February 2020 I became a 'Card Angel' for Chemo Angels***April 2020 I became a contributor to manuptocancer.com as a blogger for ' Joe's Wolfpack Trailblazers' . A blog about the works of service and the daily lives of the men of The Howling Place. ***June 2020 I became an Ambassador for Fight CRC 2021 *** October 2020 I became an Empowered Patient Leader for Colontown.org***December 2020 Created 'Colontown Junior' with the help of Colontown.org to support the families of children diagnosed with pediatric colorectal cancer.I am married to my wife Michelle Bullock for 29 years. We live in Durham, N.C. with our two children._____________________Connect with Joe:_____________________twitter @jbullock114https://www.facebook.com/joe.bullock.7792instagram jbullock114manuptocancer.comwww.facebook.com/groups/manuptocancer/______________________________________________________This episode is sponsored by: That's why the BC Schizophrenia Society has launched a brand new podcast, called Look Again, Mental Illness Re-examined. Host Faydra Aldridge talks to doctors, families, and people with lived experience about how to recognize mental illness, and the specific treatments that can help. Check it out. They'll really challenge you to“look again” at what you think you know about mental illness. Support the show (https://www.patron.com/findyourrare)

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.11.245969v1?rss=1 Authors: Szikriszt, B., Poti, A., Nemeth, E., Kanu, N., Swanton, C., Szuts, D. Abstract: Platinum-based drugs are a mainstay of cancer chemotherapy. However, their mutagenic effect can increase tumour heterogeneity, contribute to the evolution of treatment resistance, and also induce secondary malignancies. We coupled whole genome sequencing with phenotypic investigations on two cell line models to compare the magnitude and understand the mechanism of mutagenicity of cisplatin, carboplatin and oxaliplatin. Cisplatin induced significantly more base substitution mutations than carboplatin or oxaliplatin when used at equitoxic concentrations on human TK6 or chicken DT40 cells, and also induced the highest number of short insertions and deletions. Assessment through histone H2AX phosphorylation and single cell agarose gel electrophoresis suggested that cisplatin caused more DNA damage than carboplatin or oxaliplatin. The analysis of base substitution spectra revealed that all three tested platinum drugs elicit both a direct mutagenic effect at purine dinucleotides, and an indirect effect of accelerating endogenous mutagenic processes. Whereas the direct mutagenic effect correlated with the level of DNA damage caused, the indirect mutagenic effects were equal. The different mutagenicity and DNA damaging effect of equitoxic platinum drug treatments suggests that DNA damage independent mechanisms significantly contribute to their cytotoxicity. Thus, the comparatively high mutagenicity of cisplatin should be taken into account in the design of chemotherapeutic regimens. Copy rights belong to original authors. Visit the link for more info

In this week's episode of the Spine & Nerve podcast, Dr. Brian Joves and Dr. Nicolas Karvelas begin a new journal club format to discuss multiple articles that have a similar theme. The goal of this series on the podcast is to summarize recent research, and provide a discussion of some key points in regards to potential impact on clinical care. In this week's podcast the doctors summarize and discuss three recent articles regarding medications for treatment of chronic pain. Please see References section below for the articles discussed in today's podcast. References: 1. Alberti P, et al. Topiramate prevents Oxaliplatin-related axonal hyperexcitability and oxaliplatin induced peripheral neurotoxicity. Neuropharmacology. 2020. 2. Karin Bruun-Plesner, MD, Morten Rune Blichfeldt-Eckhardt, MD, PhD, Henrik Bjarke Vaegter, MSc, PhD, Joergen T Lauridsen, MSc, PhD, Kirstine Amris, MD, MedScD, Palle Toft, MD, PhD, MedScD. Low-Dose Naltrexone for the Treatment of Fibromyalgia: Investigation of Dose–Response Relationships. Pain Medicine. 2020. 3. Lynn Webster, MD, Jeffrey Gudin, MD, Robert B Raffa, PhD, Jay Kuchera, MD, Richard Rauck, MD, Jeffrey Fudin, PharmD, Jeremy Adler, DMSc, PA-C, Theresa Mallick-Searle, NP. Understanding Buprenorphine for Use in Chronic Pain: Expert Opinion. Pain Medicine. 2020. Follow our practice on Facebook at Spine & Nerve Diagnostic Center. Please leave us a comment or review- these help us to improve and provide value to more people. This podcast is for information and educational purposes only, it is not meant to be medical advice. If anything discussed may pertain to you, please seek council with your healthcare provider. The views expressed are those of the individuals expressing them, they may not represent the views of Spine & Nerve.

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. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today, I'm interviewing Dr. Nancy Baxter from St. Michael's Hospital in Toronto, senior author on "Duration of Oxaliplatin-Containing Adjuvant Therapy for Stage III Colon Cancer: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Baxter. Thanks very much, Shannon, for speaking with me. I'm happy to share our work developing this guideline. So first, can you give us a general overview of what this guideline covers and the studies which provide the evidence? Absolutely. So use of adjuvant therapy for patients with stage III colon cancer is common, and it's effective. We know that these patients are at substantial risk of recurrence of their disease and that adjuvant therapy can reduce that risk. But we also know that comes with a cost. The most effective adjuvant therapy is FOLFOX or oxaliplatin-containing chemotherapy regimens. And we know that a really substantial number of people will end up with neurotoxicity, with peripheral sensory neurotoxicity, that can be long lasting and certainly affects their quality of life. So the whole question was whether the duration of oxaliplatin-containing chemotherapeutic regimens could be shortened when they're used for adjuvant therapy, so if we could give three months instead of six months. Because we know that if we give three months of therapy, the risk of neurotoxicity is much lower. So if we had the same effectiveness with the shorter duration, then we could spare patients the negative consequences of the agent given for a longer period of time. So in developing these guidelines, we looked at the results of international group of trials, the six trials from the IDEA collaboration. So these were six randomized trials in various jurisdictions that tried to look at this question, so three months of an oxaliplatin-based chemotherapeutic regimen for adjuvant therapy for stage III cancer versus six months duration of therapy. And so there was a planned analysis to bring all of these data together to develop the evidence base to make this recommendation. So our guideline and our systematic review basically identified this is the key piece of literature to base our recommendations and guidelines on. That's essentially the main study, so the meta-analysis of these six randomized controlled trials that formed the basis of the IDEA collaboration. So the IDEA collaboration studies-- there were six individual randomized trials that formed part of the IDEA collaboration. And they were conducted in Italy, Greece, Japan, North America, through CALGB/SWOG, the UK, Denmark, Spain, Australia, Sweden, and New Zealand, as well as France. So data came from, really, around the world. The median age of people in the studies was 64 years of age. And these people had a really good performance status, so almost all of these patients had an ECOG performance status of 0 or 1. So they were healthy patients that were in the study. And so some patients received CAPOX, and some received FOLFOX. That wasn't part of the randomization scheme. Other than the CALGB/SWOG study, this was up to the discretion of the investigator or patient. In the SWOG/CALGB study, only FOLFOX was given. And the authors planned a prespecified subgroup analysis to look at differences between CAPOX and FOLFOX. There was also a prespecified analysis to look at differences based on stage. What they found when they looked at the results was that, overall, the difference between groups in terms of the three months versus six months was that the hazard ratio between these two was 1.07, meaning a small difference between the groups in terms of recurrence or death between three months and six months overall. But because the prespecified confidence interval, noninferiority interval, for the difference in outcome was 1.12, the 95% confidence interval for the hazard ratio was above this. So it was 1.15, indicating that this prespecified noninferiority margin was exceeded. And so the study did not prove noninferiority of the three-month regimen. So we're left with an inconclusive result. So that's why our guidelines don't have a strong recommendation for the three months, because we can't rule out a small but potentially important difference between the two groups in terms of recurrence or death. Now, interestingly, when they looked at the prespecified subgroup analysis, which was looking at CAPOX versus FOLFOX, a difference was found. So they actually found that for FOLFOX chemotherapy, three months of therapy was inferior to six months of therapy, while for CAPOX, actually, three months and six months were the same. So it met the criteria of noninferiority. So these are kind of two different conclusions based on which type of chemotherapy was used. This was surprising to the investigators and was not expected. And certainly, it was not consistent with the randomized trials that we have comparing these regimens. So we therefore did not make any conclusions in our recommendations about CAPOX versus FOLFOX. But this is certainly something that requires further investigation in the future. In terms of stage, we did not find that there was an interaction between T stage or end stage when you looked at the differences between the three and the six month. And that was the prespecified analysis. But in non-prespecified analysis, which was the higher risk versus lower risk categories, you did find this difference where the patients with high-risk disease had inferior disease-free survival with three months versus six months of therapy, while those at low risk of disease, it seemed quite safe to give three months versus six months. So that's a long story. But essentially, because the high risk versus low risk analysis was not prespecified, there's a limitation to how strong our recommendations can be to have three months of therapy. However, given that the hazard ratio associated with three months versus six months of therapy for this lower risk group was only 1.01, indicating they were the same, and the risk of neuropathy was substantially higher with six months, this has led to us making recommendations that the three months of therapy is adequate for patients with low-risk disease after discussion with patients about the possible pros and cons. And what are the key recommendations of this guideline? Well, so the recommendations of this guideline do depend on the pathology, so how high risk the patient is. So based on the evidence from the IDEA collaboration, the researchers found that patients who had a high risk of recurrence-- so had T4 disease or heavily node-positive disease, N2 disease-- the six-month duration of therapy was better than the three-month duration of therapy. These studies and the meta-analysis were designed as noninferiority meta-analyses. But it was clear from the results that the three-month duration was inferior when compared to three months for these high-risk patients. So that seems clear, although we know that those patients will also be at more risk of neuropathy. And so that needs to be discussed with patients, as well. So for the second group, which are patients who are at lower risk of recurrence, what we found was there was less of a clear benefit of six months of therapy. The recommendation was that patients who are in this low-risk category-- so T1, T2, or T3 cancers that are N1, so not heavily node-positive-- clinicians can offer three months versus six months of therapy after having a discussion with their patients about the pros and cons of that. So the clinicians can go ahead and offer that to patients and still be within the common guidelines based on evidence for treatment of stage III colon cancer. So because there's some uncertainty after analysis of the IDEA collaboration, one of the really important recommendations that we make is about this shared decision-making approach. So the third recommendation that we make is that oncologists should discuss these factors with their patients who have stage III resected colon cancer and that the duration of therapy needs to take into account the tumor characteristics-- the surgical resection, the number of lymph nodes examined, the comorbidities, the patient functional status, all of these various things-- and there needs to be a discussion of the potential for benefit and the risk of harm based on the duration of therapy. And oncologists definitely discuss these things with their patients. And this just emphasizes how this is yet another component of the discussion that needs to be included, particularly when speaking with low-risk patients who are at substantial risk of harm from neuropathy and are unlikely to benefit greatly by extending chemotherapy to six months. So why is this guideline so important? And how will it change practice? Well, I think, until now, the standard recommendation has been six months of FOLFOX or six months of oxaliplatin-based chemotherapy. And again, there are many patients who have quality of life-affecting neuropathy because of this. So for a substantial proportion of patients who present to us with stage III cancer-- so those that are low risk-- I think this provides some options to them. So they can opt for a shorter duration of chemotherapy with a lower risk of toxicity. This saves time. This saves cost to the patient and to the system and potentially improves their quality of life without a great impact on outcome in terms of disease recurrence. So that's a substantial number, a substantial proportion of our patients, who can be treated in this way. So I think that this is a real benefit. Again, oncologists need to have a conversation with their patients about the pros and cons. But this is an option for their patients, whereas from an evidence-based perspective, it wasn't before the publication of the IDEA collaboration. Finally, how will these guideline recommendations affect patients? So for patients who have heavily node-positive disease-- so high-risk patients with T4 or N2 disease-- it's not going to affect care. So the expectation would be those patients would be treated with six months of therapy, similar to previous recommendations. So this will be for people who are at lower risk of disease recurrence, so patients with T1 to 3 tumors that are N1 positive, so not heavily node positive. So these patients will have the opportunity to opt for a shorter duration of therapy. So that's a major benefit to patients. Again, it's important that there's a discussion and that patients understand the pros and cons. But this is now an option for them, which is excellent. Thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, please go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Com o objetivo de comparar Mitomicina C vs. Oxaliplatina na HIPEC para pacientes com Câncer Colorretal, os autores desse paper avaliaram, de modo retrospectivo, mais de 200 pacientes em termos de sobrevida. O dr. David Morris e seus colaboradores concluíram que os pacientes que receberam oxaliplatina (n=106) durante a HIPEC tiveram melhores taxas de sobrevida global (56 vs. 29m) quando comparados com os que usaram mitomicina (n=96). Interessante dizer que a sobrevida livre de doença foi igual! https://www.ncbi.nlm.nih.gov/pubmed/27780675 Quer saber mais sobre a discussão desse trabalho? Acesse o spotify ou podcast no seu smartphone, ou acesse o nosso site: www.clinicalpaperspodcast.com.br

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. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today, I'm interviewing Dr. Nancy Baxter from St. Michael's Hospital in Toronto, senior author on "Duration of Oxaliplatin-Containing Adjuvant Therapy for Stage III Colon Cancer: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Baxter. Thanks very much, Shannon, for speaking with me. I'm happy to share our work developing this guideline. So first, can you give us a general overview of what this guideline covers and the studies which provide the evidence? Absolutely. So use of adjuvant therapy for patients with stage III colon cancer is common, and it's effective. We know that these patients are at substantial risk of recurrence of their disease and that adjuvant therapy can reduce that risk. But we also know that comes with a cost. The most effective adjuvant therapy is FOLFOX or oxaliplatin-containing chemotherapy regimens. And we know that a really substantial number of people will end up with neurotoxicity, with peripheral sensory neurotoxicity, that can be long lasting and certainly affects their quality of life. So the whole question was whether the duration of oxaliplatin-containing chemotherapeutic regimens could be shortened when they're used for adjuvant therapy, so if we could give three months instead of six months. Because we know that if we give three months of therapy, the risk of neurotoxicity is much lower. So if we had the same effectiveness with the shorter duration, then we could spare patients the negative consequences of the agent given for a longer period of time. So in developing these guidelines, we looked at the results of international group of trials, the six trials from the IDEA collaboration. So these were six randomized trials in various jurisdictions that tried to look at this question, so three months of an oxaliplatin-based chemotherapeutic regimen for adjuvant therapy for stage III cancer versus six months duration of therapy. And so there was a planned analysis to bring all of these data together to develop the evidence base to make this recommendation. So our guideline and our systematic review basically identified this is the key piece of literature to base our recommendations and guidelines on. That's essentially the main study, so the meta-analysis of these six randomized controlled trials that formed the basis of the IDEA collaboration. So the IDEA collaboration studies-- there were six individual randomized trials that formed part of the IDEA collaboration. And they were conducted in Italy, Greece, Japan, North America, through CALGB/SWOG, the UK, Denmark, Spain, Australia, Sweden, and New Zealand, as well as France. So data came from, really, around the world. The median age of people in the studies was 64 years of age. And these people had a really good performance status, so almost all of these patients had an ECOG performance status of 0 or 1. So they were healthy patients that were in the study. And so some patients received CAPOX, and some received FOLFOX. That wasn't part of the randomization scheme. Other than the CALGB/SWOG study, this was up to the discretion of the investigator or patient. In the SWOG/CALGB study, only FOLFOX was given. And the authors planned a prespecified subgroup analysis to look at differences between CAPOX and FOLFOX. There was also a prespecified analysis to look at differences based on stage. What they found when they looked at the results was that, overall, the difference between groups in terms of the three months versus six months was that the hazard ratio between these two was 1.07, meaning a small difference between the groups in terms of recurrence or death between three months and six months overall. But because the prespecified confidence interval, noninferiority interval, for the difference in outcome was 1.12, the 95% confidence interval for the hazard ratio was above this. So it was 1.15, indicating that this prespecified noninferiority margin was exceeded. And so the study did not prove noninferiority of the three-month regimen. So we're left with an inconclusive result. So that's why our guidelines don't have a strong recommendation for the three months, because we can't rule out a small but potentially important difference between the two groups in terms of recurrence or death. Now, interestingly, when they looked at the prespecified subgroup analysis, which was looking at CAPOX versus FOLFOX, a difference was found. So they actually found that for FOLFOX chemotherapy, three months of therapy was inferior to six months of therapy, while for CAPOX, actually, three months and six months were the same. So it met the criteria of noninferiority. So these are kind of two different conclusions based on which type of chemotherapy was used. This was surprising to the investigators and was not expected. And certainly, it was not consistent with the randomized trials that we have comparing these regimens. So we therefore did not make any conclusions in our recommendations about CAPOX versus FOLFOX. But this is certainly something that requires further investigation in the future. In terms of stage, we did not find that there was an interaction between T stage or end stage when you looked at the differences between the three and the six month. And that was the prespecified analysis. But in non-prespecified analysis, which was the higher risk versus lower risk categories, you did find this difference where the patients with high-risk disease had inferior disease-free survival with three months versus six months of therapy, while those at low risk of disease, it seemed quite safe to give three months versus six months. So that's a long story. But essentially, because the high risk versus low risk analysis was not prespecified, there's a limitation to how strong our recommendations can be to have three months of therapy. However, given that the hazard ratio associated with three months versus six months of therapy for this lower risk group was only 1.01, indicating they were the same, and the risk of neuropathy was substantially higher with six months, this has led to us making recommendations that the three months of therapy is adequate for patients with low-risk disease after discussion with patients about the possible pros and cons. And what are the key recommendations of this guideline? Well, so the recommendations of this guideline do depend on the pathology, so how high risk the patient is. So based on the evidence from the IDEA collaboration, the researchers found that patients who had a high risk of recurrence-- so had T4 disease or heavily node-positive disease, N2 disease-- the six-month duration of therapy was better than the three-month duration of therapy. These studies and the meta-analysis were designed as noninferiority meta-analyses. But it was clear from the results that the three-month duration was inferior when compared to three months for these high-risk patients. So that seems clear, although we know that those patients will also be at more risk of neuropathy. And so that needs to be discussed with patients, as well. So for the second group, which are patients who are at lower risk of recurrence, what we found was there was less of a clear benefit of six months of therapy. The recommendation was that patients who are in this low-risk category-- so T1, T2, or T3 cancers that are N1, so not heavily node-positive-- clinicians can offer three months versus six months of therapy after having a discussion with their patients about the pros and cons of that. So the clinicians can go ahead and offer that to patients and still be within the common guidelines based on evidence for treatment of stage III colon cancer. So because there's some uncertainty after analysis of the IDEA collaboration, one of the really important recommendations that we make is about this shared decision-making approach. So the third recommendation that we make is that oncologists should discuss these factors with their patients who have stage III resected colon cancer and that the duration of therapy needs to take into account the tumor characteristics-- the surgical resection, the number of lymph nodes examined, the comorbidities, the patient functional status, all of these various things-- and there needs to be a discussion of the potential for benefit and the risk of harm based on the duration of therapy. And oncologists definitely discuss these things with their patients. And this just emphasizes how this is yet another component of the discussion that needs to be included, particularly when speaking with low-risk patients who are at substantial risk of harm from neuropathy and are unlikely to benefit greatly by extending chemotherapy to six months. So why is this guideline so important? And how will it change practice? Well, I think, until now, the standard recommendation has been six months of FOLFOX or six months of oxaliplatin-based chemotherapy. And again, there are many patients who have quality of life-affecting neuropathy because of this. So for a substantial proportion of patients who present to us with stage III cancer-- so those that are low risk-- I think this provides some options to them. So they can opt for a shorter duration of chemotherapy with a lower risk of toxicity. This saves time. This saves cost to the patient and to the system and potentially improves their quality of life without a great impact on outcome in terms of disease recurrence. So that's a substantial number, a substantial proportion of our patients, who can be treated in this way. So I think that this is a real benefit. Again, oncologists need to have a conversation with their patients about the pros and cons. But this is an option for their patients, whereas from an evidence-based perspective, it wasn't before the publication of the IDEA collaboration. Finally, how will these guideline recommendations affect patients? So for patients who have heavily node-positive disease-- so high-risk patients with T4 or N2 disease-- it's not going to affect care. So the expectation would be those patients would be treated with six months of therapy, similar to previous recommendations. So this will be for people who are at lower risk of disease recurrence, so patients with T1 to 3 tumors that are N1 positive, so not heavily node positive. So these patients will have the opportunity to opt for a shorter duration of therapy. So that's a major benefit to patients. Again, it's important that there's a discussion and that patients understand the pros and cons. But this is now an option for them, which is excellent. Thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, please go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Dr Iveson speaks with ecancer at ASCO 2017 about results from the SCOT trial, a non-inferiority assessment of adjuvant oxaliplatin chemotherapy for 3 or 6 months to treat colorectal cancer. He describes how, by meeting these non-inferiority endpoints, 3 months of oxaliplatin can reduce cost for healthcare providers and improve patient quality of life, with less risk of peripheral neuropathy. The SCOT trial contributes to a larger international trial schema called IDEA, an international collaborative assessment of oxaliplatin with capecitabine or FOLFIRI at different fractions and staging. Findings within IDEA have identified high and low risk groups, Dr Iveson encourages to be considered eligible for 3 months CapOx.

Thu, 10 Jul 2014 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/17208/ https://edoc.ub.uni-muenchen.de/17208/1/Stieg_Mareike.pdf Stieg, Mareike

This trial supports the use of neoadjuvant capecitabine monotherapy as a potentially more convenient radiosensitizer that does not sacrifice surgical and pathologic outcomes in rectal cancer. However, further study is needed.

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.

Thu, 18 Oct 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15147/ https://edoc.ub.uni-muenchen.de/15147/1/Novotna_Jaroslava.pdf Novotna, Jaroslava ddc:610, ddc:6

Colorectal Cancer

As oncologists treat an increasing number of older patients with colon cancer, and as treatment options improve for older patients, oncologists should work with geriatricians to make the best treatment decisions.

This podcast reviews a negative phase III clinical trial of cetuximab combined with chemotherapy in first-line metastatic colorectal cancer and focuses on the interaction of targeted therapy combined with chemotherapy.

Background: To evaluate the value of KRAS codon 13 mutations in patients with advanced colorectal cancer (advanced CRC) treated with oxaliplatin and fluoropyrimidines. Methods: Tumor specimens from 201 patients with advanced CRC from a randomized, phase III trial comparing oxaliplatin/5-FU vs. oxaliplatin/capecitabine were retrospectively analyzed for KRAS mutations. Mutation data were correlated to response data (Overall response rate, ORR), progression-free survival (PFS) and overall survival (OS). Results: 201 patients were analysed for KRAS mutation (61.2% males; mean age 64.2 +/- 8.6 years). KRAS mutations were identified in 36.3% of tumors (28.8% in codon 12, 7.4% in codon 13). The ORR in codon 13 patients compared to codon 12 and wild type patients was significantly lower (p = 0.008). There was a tendency for a better overall survival in KRAS wild type patients compared to mutants (p = 0.085). PFS in all patients was not different in the three KRAS genetic groups (p = 0.72). However, we found a marked difference in PFS between patients with codon 12 and 13 mutant tumors treated with infusional 5-FU versus capecitabine based regimens. Conclusions: Our data suggest that the type of KRAS mutation may be of clinical relevance under oxaliplatin combination chemotherapies without the addition of monoclonal antibodies in particular when overall response rates are important.

The addition of oxaliplatin to fluorouracil-based neoadjvuant chemoradiation for locally advanced rectal cancer significantly increases toxicity but does not improve the pathologic complete response rate.

Diese dreiarmige Phase-II-Studie ist die erste prospektive randomisierte Studie, die drei verschiedene Zweifach-Kombinations-Chemotherapien beim fortgeschrittenen duktalen Adenokarzinom des Pankreas vergleicht. Die Daten zum Zeitpunkt der Auswertung sind insbesondere bezüglich dem primären Zielkriterium Progressfreies Überleben (PFS) und dem sekundären Zielkriterium Gesamtüberleben (OS) und bezüglich der Auswertungen der Nebenwirkungen als reif anzusehen. Die Ausgangskriterien und die Strata sind relativ gut über die drei Arme verteilt. Im Median sind die Patienten 63 Jahre alt. Bei der überwiegenden Mehrheit der Patienten (82%) liegt ein metastasiertes Stadium vor, 68% hatten nachgewiesene Metastasen in der Leber. Ein Großteil der Patienten hat bei Einschluss einen ordentlichen KPS (84% mit KPS ≥80%) aufgewiesen. Keine der drei Kombinationen hat den primären Endpunkt einer Rate des PFS nach 3 Monaten von über 70% erreicht. Das PFS nach 3 Monaten lag aber für die randomisierten Patienten insgesamt mit 60% (95%-KI: 54% - 68%) über dem unter einer Gemcitabin- Therapie zu erwartenden PFS nach 3 Monaten von 50%. Hier schneidet im Trend der CAPGEM-Arm mit 64% (95%-KI: 53% - 77%) und der mGEMOX-Arm mit 60% (95%- KI: 49% - 74%) etwas besser ab als der CAPOX-Arm mit 51% (95%-KI 40% - 65%). Der Median des PFS als sekundäres Zielkriterium wurde im CAPGEM-Arm mit 5,7 Monaten geschätzt. Dies war im Trend besser als unter CAPOX (p=0,42) mit 4,2 Monaten und unter mGEMOX (p = 0,47) mit 3,9 Monaten. Die Gesamtansprechrate (ORR) als weiterer sekundärer Endpunkt war ebenfalls im CAPGEM-Arm mit 25% im Trend besser als die mit jeweils 13% identischen Ergebnisse im CAPOX-Arm und mGEMOX-Arm (jeweils p = 0,11). Beim sekundären Zielkriterium medianes Gesamt-Überleben (OS) besteht zwischen den Behandlungsarmen kein statistisch signifikanter Unterschied, es erreichte 8,1 Monate für CAPOX, 9,0 Monate für CAPGEM und 6,9 Monate für mGEMOX. Insgesamt ist die Effektivität der drei Therapiearme bezüglich der Zielkriterien PFS nach 3 Monaten und OS statistisch nicht signifikant unterschiedlich. Bei den paarweisen Vergleichen ergibt sich aber ein Trend im PFS, in der objektiven Remissionsrate und im medianen Gesamtüberleben (OS) zuungunsten des mGEMOX-Arms. Bei Betrachtung der Sicherheit sind die Häufigkeiten von Grad-3- oder Grad-4-Nebenwirkungen insgesamt mäßig. Alle drei Therapiemodalitäten konnten bei vertretbarer Verträglichkeit gegeben werden. Es konnten jedoch signifikante Unterschiede im Spektrum der Nebenwirkungen beobachtet werden. Die hämatologische Toxizität ist signifikant am geringsten im CAPOX-Arm (p