{"id":266,"date":"2019-10-09T21:32:26","date_gmt":"2019-10-09T16:02:26","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=266"},"modified":"2019-10-09T21:32:26","modified_gmt":"2019-10-09T16:02:26","slug":"prevention-treatment-of-chemotherapy-induced-nausea-vomiting","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/prevention-treatment-of-chemotherapy-induced-nausea-vomiting\/","title":{"rendered":"Prevention &#038; Treatment of Chemotherapy-Induced Nausea &#038; Vomiting"},"content":{"rendered":"\n<p><strong>Prevention and Treatment of Chemotherapy-Induced Nausea and\nVomiting<\/strong><\/p>\n\n\n\n<p>Three distinct types of CINV have been defined, with important\nimplications for both prevention and management:<\/p>\n\n\n\n<ul><li><strong>Acute emesis,<\/strong> which most commonly begins within one to two hours of chemotherapy and usually peaks in four to six hours<\/li><li><strong>Delayed emesis,<\/strong> occurring more than 24 hours after chemotherapy<\/li><li><strong>Anticipatory emesis,<\/strong> occurring prior to treatment as a conditioned response in patients who have developed significant nausea and vomiting during previous cycles of chemotherapy<\/li><\/ul>\n\n\n\n<p><strong>OVERVIEW OF THE APPROACH TO PROPHYLAXIS<\/strong><\/p>\n\n\n\n<ul><li><strong>Estimating the risk of nausea and vomiting<\/strong> \u2014 The most important factor determining the likelihood of acute or delayed emesis developing during chemotherapy is the <strong>intrinsic emetogenicity of the particular agent. <\/strong><\/li><li><strong>other factors<\/strong><ul><li>patient age, <\/li><\/ul><ul><li>sex, and <\/li><\/ul><ul><li>history of alcohol consumption, <\/li><\/ul><\/li><\/ul>\n\n\n\n<p><strong>Chemotherapy agents were divided into four categories based upon\nthe risk of emesis in the absence of antiemetic prophylaxis:<\/strong><\/p>\n\n\n\n<p>\u25cf<strong>Highly emetic<\/strong> \u2013 &gt;90 percent risk of emesis <strong>Anthracycline\/cyclophosphamide<\/strong> for breast cancer<br>(<strong>Carmustine, Cisplatin, Cyclophosphamide \u22651500 mg\/m2, Dacarbazine, Mechlorethamine, Streptozocin<\/strong>)<br>\u25cf<strong>Moderately emetic<\/strong> \u2013 &gt;30 to 90 percent risk of emesis<br>\u25cf<strong>Low emetogenicity<\/strong> \u2013 10 to 30 percent risk of emesis<br>\u25cf<strong>Minimally emetic<\/strong> \u2013 &lt;10 percent risk of emesis<\/p>\n\n\n\n<p>For\ncombination regimens, the emetic level is determined by identifying the most\nemetic agent in the combination and then assessing the relative contribution of\nthe other agents. <\/p>\n\n\n\n<p>As an\nexample, cyclophosphamide and doxorubicin are both moderately emetogenic\nagents, but when given together, the regimen is highly emetic. <\/p>\n\n\n\n<p><strong>Choosing the prophylactic strategy \u2014<\/strong><\/p>\n\n\n\n<p>The three\ncategories of drugs with the highest therapeutic index for the management of\nCINV are <\/p>\n\n\n\n<ul><li>(5-HT3) receptor antagonists, <\/li><li>the neurokinin-1 receptor (NK1R)\nantagonists, <\/li><li>and glucocorticoids (especially\ndexamethasone). <\/li><li>antipsychotic medication <strong>olanzapine<\/strong>. <\/li><\/ul>\n\n\n\n<p><strong>An important point is that virtually all of the clinical trials\nevaluating CINV have focused on intravenously delivered chemotherapy. <\/strong><\/p>\n\n\n\n<p>Therefore,\nevidence-based guidelines for antiemetic prophylaxis with oral chemotherapy\nagents are not currently possible. <\/p>\n\n\n\n<p><strong>Highly emetogenic chemotherapy<\/strong><\/p>\n\n\n\n<p><strong>Cisplatin and other highly emetogenic single agents<\/strong><\/p>\n\n\n\n<p>\u25cfDay 1 \u2013 a combination of an NK1R antagonist, a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. <br>\u25cfDays 2 to 4 \u2013 continuing dexamethasone (days 2 to 4) and continuing olanzapine (days 2 to 4).<\/p>\n\n\n\n<p>If\naprepitant is used on day 1, we recommend continuing aprepitant on days 2 and\n3.<\/p>\n\n\n\n<p>All other\nNK1R antagonists (i.e., fosaprepitant, rolapitant, netupitant) are administered\non day 1 only.<\/p>\n\n\n\n<p><strong>Moderately emetogenic chemotherapy<\/strong><\/p>\n\n\n\n<p><strong>Carboplatin-based regimens<\/strong><\/p>\n\n\n\n<p>\u25cfDay 1 \u2013 a combination of an NK1R antagonist, a 5-HT3 receptor antagonist, and dexamethasone on day 1.<br>\u25cf<em>No additional prophylaxis<\/em> beyond day 1 for delayed emesis is recommended. <\/p>\n\n\n\n<p><strong>Non-carboplatin-based regimens<\/strong><\/p>\n\n\n\n<p>\u25cfDay 1 \u2013 a combination of a 5-HT3 receptor antagonist plus dexamethasone on day 1.<br>\u25cfDays 2 to 3 \u2013 To prevent delayed emesis if the regimen contains agents with known potential to induce delayed emesis (eg, oxaliplatin), we suggest single-agent treatment with dexamethasone on days 2 and 3. <\/p>\n\n\n\n<p>If a\nfirst-generation 5-HT3 receptor antagonist is used rather than palonosetron on\nday 1, then treatment with a first-generation 5-HT3 receptor antagonist alone\non days 2 and 3 is a reasonable alternative. <\/p>\n\n\n\n<p><strong>Low emetogenic chemotherapy<\/strong><\/p>\n\n\n\n<p>\u25cf <strong><em>dexamethasone\n(4 to 8 mg) as a single agent.<\/em><\/strong> <\/p>\n\n\n\n<p>glucocorticoid\nuse is contraindicated \u00e0\na single dose of a drug such as <strong><em>prochlorperazine or a 5-HT3 receptor\nantagonist.<\/em><\/strong> <\/p>\n\n\n\n<p>This\npatient population generally does not require prophylaxis against delayed\nemesis. <\/p>\n\n\n\n<p><strong>Minimally emetogenic chemotherapy<\/strong><\/p>\n\n\n\n<p>\u25cf\nantiemetic therapy not be routinely administered <\/p>\n\n\n\n<p>Prophylactic\nantiemetics (dexamethasone 4 to 8 mg, prochlorperazine, or metoclopramide) may\nbe administered to patients who have had emesis with prior low-risk regimens,\nor on an &#8220;as needed&#8221; basis. <\/p>\n\n\n\n<p><strong>Anticipatory emesis<\/strong><\/p>\n\n\n\n<p>\u25cfThe\nprimary approach to the prevention of anticipatory emesis is the prevention of\nCINV beginning with the initial cycles of chemotherapy. <\/p>\n\n\n\n<p><strong>behavioral therapy and\/or\nbenzodiazepines. <\/strong><\/p>\n\n\n\n<p><strong>Poor emesis control\/rescue therapy<\/strong><\/p>\n\n\n\n<p>\u25cfFor\npatients who do not achieve adequate control of CINV with their initial\nantiemetic regimen, the patient&#8217;s management \u00e0 <\/p>\n\n\n\n<p><strong><em>Olanzapine\n5 or 10 mg daily for three days <\/em><\/strong><em>can be considered as rescue therapy for patients with breakthrough\nnausea and vomiting who did not receive olanzapine initially<\/em>.\n<\/p>\n\n\n\n<p>For\npatients <em>already receiving olanzapine<\/em>,\n\u00e0\nagent from a different class than was used for initial prophylaxis (eg, <em>prochlorperazine).<\/em><\/p>\n\n\n\n<p>\u25cf<strong>The modest antiemetic activity of\ncannabinoids and their unfavorable side effect profile, especially in older\npatients, limit the clinical utility of this class of agents for the treatment\nof refractory CINV.<\/strong> <\/p>\n\n\n\n<p>Nevertheless,\nguidelines from NCCN and ASCO state that cannabinoids can be considered for\nrefractory nausea and vomiting, and as a rescue antiemetic. <\/p>\n\n\n\n<p><strong>ANTIEMETIC EFFICACY OF INDIVIDUAL AGENTS \u2014 <\/strong><\/p>\n\n\n\n<ol><li><strong>5-HT3\nreceptor antagonists \u2014<\/strong><\/li><li>has a high therapeutic index for the prevention\nof CINV.<\/li><li>more effective than less-specific\nagents such as high-dose metoclopramide and as effective as the combination of\nhigh-dose metoclopramide and dexamethasone. <\/li><li>When are used in combination with\ndexamethasone, they are more effective than high-dose metoclopramide plus\ndexamethasone. <\/li><\/ol>\n\n\n\n<p>first-generation\n5-HT3 receptor antagonists <\/p>\n\n\n\n<ul><li>azasetron, <\/li><li>dolasetron, <\/li><li>granisetron, <\/li><li>ondansetron, <\/li><li>ramosetron, and <\/li><li>tropisetron <\/li><\/ul>\n\n\n\n<ul><li>An <strong>orally disintegrating formulation of ondansetron<\/strong> also is available,\u00e0formulation\nmay be particularly useful for patients with dysphagia or anorexia. <\/li><\/ul>\n\n\n\n<ul><li>A <strong>granisetron\ntransdermal system<\/strong> \u00e0\n<strong>extended-release subcutaneous\nformulation<\/strong> \u00e0\napproved by the US FDA in August 2016 \u00e0\nfor the prevention of acute and delayed nausea and vomiting associated with\ninitial and repeat courses of moderately emetogenic chemotherapy, or\ncombination anthracycline and cyclophosphamide chemotherapy regimens. <\/li><\/ul>\n\n\n\n<p>\u25cf first-generation\n5-HT3 receptor antagonists <strong>all appear\nequally effective<\/strong> <\/p>\n\n\n\n<p>\u25cfThere is\na <strong>plateau in therapeutic efficacy at a\ndefinable dose level<\/strong> for each drug, and further dose escalation does not\nimprove outcomes.<\/p>\n\n\n\n<p>\u25cfA <strong>single dose of a 5-HT3 receptor antagonist\nprior to chemotherapy is therapeutically equivalent to a multiple-dose schedule.<\/strong><\/p>\n\n\n\n<p>\u25cfThe <strong>efficacy <\/strong>of 5-HT3 receptor antagonists\nis <strong>significantly improved<\/strong> when they\nare <strong>combined with glucocorticoids. <\/strong><\/p>\n\n\n\n<p>\u25cf<strong>Oral formulations of these agents are as\neffective as IV formulations<\/strong>. <\/p>\n\n\n\n<p>Electrocardiogram\n(ECG) interval changes are a class effect of the first-generation 5-HT3\nantagonists and are not been reported with transdermal granisetron or\nextended-release subcutaneous granisetron <\/p>\n\n\n\n<p><strong>ECG interval changes<\/strong> appear to be <strong>most prominent one to two hours after a dose of these agents, are\nmostly small and clinically insignificant, and return to baseline within 24\nhours<\/strong>. <\/p>\n\n\n\n<p>potentially\nfatal cardiac arrhythmias, including torsade de pointes (TdP), <\/p>\n\n\n\n<p>warnings\/precautions\nregarding cardiotoxicity of these agents from the FDA.<\/p>\n\n\n\n<p><strong>Dolasetron \u2014 Due to the risk of QTc prolongation from increased\ndrug exposure, the injection form of dolasetron is contraindicated for\nprophylaxis of CINV in both children and adults<\/strong>. <\/p>\n\n\n\n<p><strong>Ondansetron<\/strong> \u2014 The FDA has issued a warning about <strong>QTc prolongation and potentially fatal\ncardiac arrhythmias<\/strong> in patients treated with ondansetron. at a single IV\ndose of <strong>32 mg<\/strong><\/p>\n\n\n\n<p><strong>Revised labeling <\/strong>in the United States includes a\nrecommendation<strong> to limit single IV doses\nto no more than 16 mg,<\/strong> <\/p>\n\n\n\n<p>Canadian\nguidelines that took effect in June 2014 place additional dosing restrictions\non IV ondansetron to mitigate the risk of QT prolongation in older adults:<\/p>\n\n\n\n<p>\u25cfAll IV\ndoses must be infused <strong>over no less than\n15 minutes.<\/strong><\/p>\n\n\n\n<p><strong>Palonosetron <\/strong>\u2014 <\/p>\n\n\n\n<p><strong>30- to 100-fold higher affinity for the 5-HT3<\/strong>\nreceptor and a significantly <strong>longer\nhalf-life (40 hours)<\/strong> compared with first-generation 5-HT3 receptor\nantagonists <\/p>\n\n\n\n<p>In contrast\nto first-generation 5-HT3 antagonists, <strong>QTc\nprolongation has not been described<\/strong> with palonosetron<\/p>\n\n\n\n<p><strong>more effective than ondansetron or dolasetron<\/strong>\nat preventing emesis due to chemotherapy agents of varying emetogenicity <\/p>\n\n\n\n<p>clinical\ntrial \u00e0\n<strong>The dose of 0.75 mg was not\nsignificantly superior compared with 0.25 mg<\/strong>. <\/p>\n\n\n\n<p><strong>Netupitant and Palonosetron Combination.<\/strong> <\/p>\n\n\n\n<p>A\ncombination of NK1 receptor antagonist plus 5HT3 receptor antagonist \u00e0 was recently approved in 2016.<\/p>\n\n\n\n<p>orally\nabout 1 h prior to chemotherapy (together with dexamethasone, at doses varying\naccording to the type of chemotherapy).<\/p>\n\n\n\n<p>When used\nin combination with glucocorticoids, palonosetron provides superior control of\ndelayed emesis compared with first-generation 5-HT3 receptor antagonists\ncombined with glucocorticoids.<\/p>\n\n\n\n<p>Updated\nantiemetic guidelines from the <strong>National\nComprehensive Cancer Network (NCCN) recommend palonosetron as the preferred\n5-HT3 antagonist<\/strong> for patients who receive moderately emetogenic\nchemotherapy.<\/p>\n\n\n\n<p>In\ncontrast, updated guidelines from the Multinational Association of Supportive\nCare in Cancer <strong>(MASCC)\/<\/strong>European\nSociety for Medical Oncology <strong>(ESMO)<\/strong>\nand the American Society of Clinical Oncology <strong>(ASCO)<\/strong> <strong>do not specify a\npreferred 5-HT3 antagonist<\/strong> for patients receiving moderately emetogenic\nchemotherapy.<\/p>\n\n\n\n<p><strong>Neurokinin-1 receptor antagonists \u2014<\/strong><\/p>\n\n\n\n<ul><li>aprepitant and fosaprepitant \u00e0 prevent\nboth acute and delayed CINV in patients receiving highly emetic,\nIV-administered chemotherapy <\/li><\/ul>\n\n\n\n<p><strong>Rolapitant<\/strong> <\/p>\n\n\n\n<p>longer\nplasma half-life (approximately seven days) than aprepitant. <\/p>\n\n\n\n<p><strong>NEPA <\/strong><strong>\u00e0<\/strong><strong> oral fixed-dose combination\ncontaining 300 mg of netupitant (a highly selective NK1R antagonist) and 0.5 mg\nof the 5-HT3 receptor antagonist palonosetron.<\/strong> <\/p>\n\n\n\n<p>Although\nfew studies have directly compared these agents head to head, <strong>the available evidence suggests that they\nhave similar efficacy for control of acute and delayed emesis, at least in the\nsetting of highly emetogenic chemotherapy<\/strong><\/p>\n\n\n\n<p><strong>An IV equivalent (IV NEPA) consisting of 235 mg of fosnetupitant,\na prodrug of netupitant, plus 0.25 mg of palonosetron <\/strong>is\nalso approved in the United States for prevention of CINV in patients receiving\nhighly emetogenic chemotherapy, largely based upon a phase III safety study\ncomparing oral versus IV NEPA. <\/p>\n\n\n\n<p><strong>Like aprepitant and fosaprepitant, netupitant is also an inhibitor\nof CYP3A4, and a reduced dose of concurrently administered glucocorticoids is\nneeded<\/strong>.<\/p>\n\n\n\n<p><strong>Glucocorticoids <\/strong>\u2014 <\/p>\n\n\n\n<ul><li>Short courses of glucocorticoids are\nwidely used both as single agents for regimens with low risk of causing CINV\nand in combination with 5-HT3 receptor inhibitors and\/or NK1R antagonists for\nmore emetic chemotherapy regimens. <\/li><li>When used in this fashion,\nglucocorticoids have a high therapeutic index. <\/li><\/ul>\n\n\n\n<p><strong>Although the various glucocorticoids are probably equally\neffective when used at an appropriate dose, <em>dexamethasone\nhas been the most extensively evaluated and is the most widely used<\/em>.<\/strong><\/p>\n\n\n\n<p><strong>Combination with a 5-HT3 antagonist \u2014 <\/strong><\/p>\n\n\n\n<p>Glucocorticoids\nalone represent insufficient first-line therapy for patients receiving either\nmoderate or highly emetic chemotherapy agents. However, <strong>the antiemetic efficacy of the 5-HT3 receptor antagonists is\nsignificantly enhanced by the addition of a glucocorticoid.<\/strong><\/p>\n\n\n\n<p><strong>single 8 mg IV dose prior to chemotherapy represented the\nappropriate dexamethasone regimen.<\/strong><\/p>\n\n\n\n<p>the dose\nof dexamethasone is reduced when it is in combination with an NK1R antagonist. <\/p>\n\n\n\n<p><strong>Olanzapine <\/strong>\u2014<\/p>\n\n\n\n<ul><li>second-generation antipsychotic <\/li><li>blocks serotonin 5-hydroxytryptamine\n(5-HT2) receptors and dopamine D2 receptors, maybe a particularly useful agent\nfor the <strong>prevention of both acute and\ndelayed nausea and vomiting<\/strong>. <\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting Three distinct types of CINV have been defined, with important implications for both prevention and management: Acute emesis, which most commonly begins within one to two hours of chemotherapy and usually peaks in four to six hours Delayed emesis, occurring more than 24 hours after chemotherapy Anticipatory[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/266"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=266"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/266\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=266"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=266"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=266"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}