Episode 296: Pharmacology 101: Anthracyclines and Other Antitumor Antibiotics

"The search for daunorubicin's sister really led to this discovery of doxorubicin, which is an analog with much greater activity. The discovery of doxorubicin can be coined kind of as, 'one of the best drugs born in Milan, Italy.' And after that, a few analogs were developed and tested, and two that we currently use today, are idarubicin and epirubicin," Puja Patel, PharmD, BCOP, clinical oncology pharmacist at the Delnor Hospital Northwestern Medicine Cancer Center in Geneva, IL, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a discussion about anthracyclines and other antitumor antibiotics. This episode is part of a series about drug classes, which we'll include a link to in the episode notes. You can earn free NCPD contact hours after listening to this episode and completing the evaluation linked below. Music Credit: " Fireflies and Stardust " by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: The learner will report an increase in knowledge of anthracyclines and antitumor antibiotics. Episode Notes The NCPD activity for this episode has expired, but you can still earn NCPD through many other ONS Podcast episodes. Find a full list of opportunities . Oncology Nursing Podcast : Pharmacology 101 series ONS Voice oncology drug reference sheets IV Cancer Treatment Education Sheets ONS Voice articles: The Evidence Is Building for ACE Inhibitors in Anthracycline-Associated Cardiotoxicity Outpatient Oncology Drug Series: Doxorubicin Is the Infamous Red Devil Clinical Journal of Oncology Nursing articles: Nursing Alchemy: Transforming R-CHOP Information Into Essentials Dyspnea: Common Side Effect Cardiac Toxicity: Using Angiotensin-Converting Enzyme Inhibitors to Prevent Anthracycline-Induced Left Ventricular Dysfunction and Cardiomyopathy Oncology Nursing Forum article: Symptom Clusters in Lymphoma Survivors Before, During, and After Chemotherapy: A Prospective Study ONS Huddle Card: Antitumor Antibiotics Additional healthcare professional resources: Blindspot: Hidden Biases of Good People Harvard University Implicit Association Test OncoPharm Podcast ASCO Education Podcast The roots of modern oncology: from discovery of new antitumor anthracyclines to their clinical use Additional patient resources: National Comprehensive Cancer Network patient resources National Comprehensive Cancer Network patient webinars National Cancer Institute resources for patients To discuss the information in this episode with other oncology nurses, visit the ONS Communities . To find resources for creating an ONS Podcast Club in your chapter or nursing community, visit the ONS Podcast Library . To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org . Highlights From Today's Episode "Anthracyclines are kind of categorized as topoisomerase II inhibitors, and these agents are very powerful in that they have—it's really like three drugs in one—they have various mechanisms." TS 3:55 "We need to create a stable environment, and so we actually cut one of the cords, and that's exactly what topoisomerase is doing. It's cutting one of the DNA strands. And in this case, it's cutting two strands, and that's why it's called topoisomerase II, so it's cutting both of the strands. It's cutting the DNA, releasing some of that tension, allowing for replication, and then rejoining that portion. So, it's a very important enzyme, and it'll go about doing this for the entire strand of DNA." TS 4:50 "The other second mechanism is kind of the effect on DNA. So, you'll come across reading the term 'DNA intercalation.' So, what does that word mean? When you take the word 'intercalate,' the definition of it means 'intrusive inserting of something in an existing series or sequence.' The analogy that I could think of here is simple: It's thinking about too many passengers squeezing in the backseat of your car. There could be safety issues, there's weight issues, there's instability maybe while driving. And that's what this doxorubicin is doing. It's sliding right in between the base pairs of the DNA double helix, destroying hydrogen bonds between those two bases, which then change the shape of that double helix. And by changing the shape, topoisomerase II, which we just talked about, can no longer go in and bind to DNA. It can't relax that super coil. And so, DNA synthesis doesn't happen." TS 6:02 "So, the main toxicity that our listeners might be familiar with is cardiotoxicity. And also with cardiotoxicity, breaking it down a little bit, there's an onset that occurs during treatment or even years to decades, and that's kind of this delayed cardiotoxicity. Signs and symptoms of acute cardiotoxicity could vary from EKG changes present as tachycardia, tachyarrhythmia. Delayed cardiotoxicity is anything from heart failure to left ventricular ejection fraction decrease." TS 9:41 "We're worried about heart failure in these patients. So, we might see EKG changes, we might see LVEF [left ventricular ejection fraction] changes, and we're kind of tracking these agents based on what is called cumulative dose tracking or lifetime dose. So, all of these agents have specific lifetime maximums that we need to be aware of." TS 14:53 "So, smoking, hypertension, diabetes, dyslipidemia, obesity, or you're older in age, or perhaps you have a compromised cardiac function—you're at greater risk for developing these cardiotoxicities. An example that I've had in my clinic is I've identified some of these patients that have these risk factors, and we go into a little bit more aggressive monitoring for the echocardiogram or MUGA [multigated acquisition]. And when we put in those orders, we often get denials from insurance. We submit the guidelines in, kind of, appeals to help those patients kind of proactively realize if we're putting them in a greater cardiac risk." TS 15:47 "One of the biggest things is for nurses to kind of look over their policies for administration for vesicants and specifically checking blood return for these agents, because many of them are given, you know, IV push. So, checking blood return every 2–5 ml is really important to make sure that you are in the right space. And then these agents, some of them can also be given continuously. So, you're thinking about, first of all, you should have a central line in for these agents because they're vesicants. But if it's being given continuous, there is something that's called anthracycline streaking, and it's not the same as an extravasation. So, I think being able to decipher the difference between the two is really, kind of, comes with experience." TS 20:36 "I think awareness is really essential. And thankfully, you know, thankfully or not, I guess, you were with the patient for this entire time, right? Because you're pushing every 2–5 ml, you're checking. So, it's a very kind of intimate experience in and of itself. So, I think just being very vigilant is very important." TS 22:24 "So, to talk about bleomycin here, for example, kinetically, two-thirds of this drug is eliminated renally. And so, we would think that there would need to be renal adjustments if there's renal changes. So, for creatinine clearance greater than 50, there are no renal dose adjustments. But after that, every 10 ml per minute decrease in GFR [glomerular filtration rate], there are dose reductions that are required. And this drug, in particular, has a lot of gradations in terms of renal dysfunction that I've seen." TS 27:30 "Thinking about bleomycin, it's IV over 10 minutes, and you want to think about the lifetime maximum dose. So, when you are working up your patient, that's something to kind of think about. Dactinomycin is highly emetogenic, so making sure that there's antibiotics on board. It's also a vesicant, so thinking about vesicants precautions. Cold compresses is how you would help treat that if there is an extravasation." TS 33:14 "I think trust is the foundation oncology really because we are asking our patients to do so many things outside of our infusion center, picking up medications, taking medications, calling us about signs and symptoms, going and getting all these imaging know. So, if there isn't that foundation of trust, having this perfect curative treatment plan may be more challenging to really be carried out." TS 38:06 "We've developed these very powerful agents, and they're non–cell specific. So, I think the next step would be, how can we reformulate them to make them less toxic and provide more of a targeted approach? And so, perhaps an antibody-drug conjugate that is specifically attacking the lymphoma or the breast cell can deliver this chemotherapy with a cytotoxic payload is there in the horizon." TS 39:07 "I think the misconception that 'I will develop heart damage' is really important. Doxorubicin has the infamous name of the red devil, but I think it's important to let your patients know that heart failure increases with cumulative dosing. You know, talking to them about 300 mg/m2 is associated with a 1.5% heart failure risk. Whereas going all the way across to 500 mg/m2, now you're looking at 6%–20% probability of developing heart failure." TS 42:30 "I think taking the time and understanding the literature. Typically, we don't start these agents with LVEF less than 50–55. There's some great review articles in JCO [Journal of Clinical Oncology] that kind of define what cardiomyopathy decrease looks like and decreases in LVEF over 10% to a value below the institutional limit of normal, I think, is a nice point to have as a value, a number to kind of work with." TS 43:53 "Working with your nurse educator and leader to help achieve OCN®, oncology certified nurse, certification is really important. And I think live simulated experiences are really beneficial, maybe even looking at extravasations or having an infusion-related reaction, because here in the acute setting, we're really kind of in this like responsive mode. But if we practice, we can respond more deliberately and more calmly." TS 45:05