Excerpt: Navari and colleagues (July 14 issue)1 report on the use of olanzapine for the prevention of chemotherapy-induced nausea and vomiting

Bossaer, John B.

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East Tennessee State University

East Tennessee State UniversityDigital Commons @ East Tennessee State UniversityETSU Faculty Works Faculty Works10-5-2016Olanzapine for Chemotherapy-Induced Nauseaand VomitingJohn B. BossaerEast Tennessee State University, bossaer@etsu.eduFollow this and additional works at: https://dc.etsu.edu/etsu-worksPart of the Oncology Commons, and the Pharmacy and Pharmaceutical Sciences CommonsThis Article is brought to you for free and open access by the Faculty Works at Digital Commons @ East Tennessee State University. It has beenaccepted for inclusion in ETSU Faculty Works by an authorized administrator of Digital Commons @ East Tennessee State University. For moreinformation, please contact digilib@etsu.edu.Citation InformationBossaer, John B.. 2016. Olanzapine for Chemotherapy-Induced Nausea and Vomiting. New England Journal of Medicine. Vol.375(14).1395-1396. https://doi.org/10.1056/NEJMc1610341 ISSN: 0028-4793Olanzapine for Chemotherapy-Induced Nausea and VomitingCopyright StatementFrom New England Journal of Medicine, John B. Bossaer, Olanzapine for Chemotherapy-Induced Nausea andVomiting, Volume 375 No. 14, Page No. 1395-1396 Copyright © 2016 Massachusetts Medical Society.Reprinted with permission.This article is available at Digital Commons @ East Tennessee State University: https://dc.etsu.edu/etsu-works/2312Correspondencen engl j med 375;14 nejm.org October 6, 2016 1395Somewhat reduced sensitivity to ticagrelor that is associated with greater platelet reactivity (i.e., a higher occurrence of high residual platelet reac-tivity during treatment) has been reported in pa-tients older than 70 years of age, independent of sex, body-mass index, diabetes, cholesterol and fi-brinogen levels, smoking, renal function, previous myocardial infarction, concomitant cardiovascu-lar therapy, hemoglobin levels, and platelet count.1 Similarly, an age older than 70 years has been inversely associated with the probability of low platelet reactivity.2 Given the above-mentioned results of the SOCRATES trial, data stratification according to a 70-year age limit may reveal a clearer distinction. Regardless of either a 65-year or 70-year limit, the possible superiority of ti-cagrelor over aspirin in reducing cardiovascular risk among younger patients should be explored further.Viktor Čulić, M.D., Ph.D.University Hospital Center Split Split, Croatia viktor . culic@ st . t-com . hrNo potential conflict of interest relevant to this letter was re-ported.1. Verdoia M, Pergolini P, Rolla R, et al. Advanced age and high-residual platelet reactivity in patients receiving dual anti-platelet therapy with clopidogrel or ticagrelor. J Thromb Hae-most 2016; 14: 57-64.2. Alexopoulos D, Xanthopoulou I, Storey RF, et al. Platelet re-activity during ticagrelor maintenance therapy: a patient-level data meta-analysis. Am Heart J 2014; 168: 530-6.DOI: 10.1056/NEJMc1610106The authors reply: As noted by Landman and Kleefstra, ticagrelor appeared more effective than aspirin in the subgroup of patients who had tak-en aspirin previously. Although this may relate to a greater effect of ticagrelor in patients who did not have a response to aspirin, it could also rep-resent a benefit from ticagrelor on a background of residual antiplatelet effects from aspirin, which persist for more than a week after a dose. A more detailed analysis is planned.PPIs were used at baseline by 585 of 6549 pa-tients (8.9%) in the ticagrelor group and by 613 of 6581 patients (9.3%) in the aspirin group. There were no significant differences in major hemor-rhage or in major and minor hemorrhage com-bined according to treatment in either PPI sub-group. Thus, the data do not support the use of aspirin by those taking a PPI, though the statis-tical power is limited.As noted by Čulić, we originally evaluated the effect of treatment among three age strata on the basis of an analysis plan that was established a priori, and ticagrelor was nominally superior to aspirin in patients younger than 65 years of age, with a trend toward significance in patients 65 to 75 years of age. When the population is stratified at 70 years of age, among those 70 years of age or younger the primary outcome event occurred in 6.2% of those assigned to ticagrelor and 7.1% of those assigned to aspirin (P = 0.09). Among those older than 70 years of age, event rates were 7.8% with ticagrelor and 8.2% with aspirin (P = 0.45). The interaction between age group and treatment was not significant (P = 0.63). Thus, we cannot confirm that age has an effect when dichotomized at 70 years.S. Claiborne Johnston, M.D., Ph.D.Dell Medical School Austin, TXPierre Amarenco, M.D.Bichat University Hospital and Medical School Paris, FranceSince publication of their article, the authors report no fur-ther potential conflict of interest.DOI: 10.1056/NEJMc1610106Olanzapine for Chemotherapy-Induced Nausea and VomitingTo the Editor: Navari and colleagues (July 14 issue)1 report on the use of olanzapine for the pre-vention of chemotherapy-induced nausea and vom-iting. The methods allowed for real-world use of neurokinin-1 (NK1)–receptor antagonists, either oral aprepitant or intravenous fosaprepitant. Al-though the dosing of dexamethasone is consis-tent on days 1 and 2 between agents, it should differ between an oral dose of 8 mg daily on days 3 and 4 in patients receiving aprepitant and an oral dose of 8 mg twice daily on days 3 and 4 in those receiving fosaprepitant.2 Because fosapre-pitant is given only on day 1, the drug interaction with dexamethasone is absent on days 3 and 4, thus necessitating a higher dexamethasone dose. Per the study protocol (available with the full text The New England Journal of Medicine Downloaded from nejm.org at J H QUILLEN COLL OF MEDICINE on May 14, 2018. For personal use only. No other uses without permission.  Copyright © 2016 Massachusetts Medical Society. All rights reserved. T h e  n e w  e ngl a nd  j o u r na l  o f  m e dic i n en engl j med 375;14 nejm.org October 6, 20161396of the article at NEJM.org), the dexamethasone dos-ing was the same regardless of which NK1-receptor antagonist was used. This approach would not have affected the results for the evaluation period of 0 to 24 hours but in effect resulted in a substan-dard comparator group for the evaluation of de-layed nausea and vomiting (in the period of 0 to 120 hours). Anecdotally, this discrepancy in dexa-methasone dosing occurs commonly in commu-nity practices, and it is important for clinicians to remain diligent with regard to the dosing of sup-portive care medications in patients receiving che-motherapy.John B. Bossaer, Pharm.D.East Tennessee State University Johnson City, TN bossaer@ etsu . eduNo potential conflict of interest relevant to this letter was re-ported.1. Navari RM, Qin R, Ruddy KJ, et al. Olanzapine for the pre-vention of chemotherapy-induced nausea and vomiting. N Engl J Med 2016; 375: 134-42.2. Emend (fosaprepitant dimeglumine). Whitehouse Station, NJ; Merck, February 2016 (package insert) (https:/ / www .merck .com/ product/ usa/ pi_circulars/ e/ emend_iv/ emend_iv_pi .pdf).DOI: 10.1056/NEJMc1610341The authors reply: Bossaer raises the issue of using a higher dose of dexamethasone on days 3 and 4 after chemotherapy than on days 1 and 2 when intravenous fosaprepitant is used in lieu of 3 days of oral aprepitant. In a trial by Grunberg et al.1 in which intravenous fosaprepitant was com-pared with 3 days of oral aprepitant and shown to be noninferior for the control of chemotherapy-induced nausea and vomiting in the delayed eval-uation period and the overall period, dexameth-asone was given in higher doses on days 3 and 4 than on days 1 and 2 in the fosaprepitant group. However, a subgroup analysis in our trial of olan-zapine showed no difference in results among pa-tients who received fosaprepitant and those who received aprepitant. In addition, recent studies have suggested that multiple days of dexametha-sone may not be necessary for the prevention of chemotherapy-induced nausea and vomiting.2,3Rudolph M. Navari, M.D., Ph.D.World Health Organization Geneva, Switzerland rmnavari@ gmail . comCharles L. Loprinzi, M.D.Mayo Clinic Rochester, MNSince publication of their article, the authors report no fur-ther potential conflict of interest.1. Grunberg S, Chua D, Maru A, et al. Single-dose fosaprepi-tant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol — EASE. J Clin Oncol 2011; 29: 1495-501.2. Celio L, Bonizzoni E, De Braud F, Agustoni F, Aapro M. Should clinicians always administer dexamethasone beyond 24 h after chemotherapy to control delayed nausea and vomiting caused by moderately emetogenic regimens? Insight from the re-evaluation of two randomized studies. Support Care Cancer 2016; 24: 1025-34.3. Matsuzaki K, Ito Y, Fukuda M, et al. Placebo-controlled phase III study comparing dexamethasone on day 1 to on day 1-3 with NK1 receptor antagonist and palonosetron in high emeto-genic chemotherapy. J Clin Oncol 2016; 34: Suppl:10019. abstract.DOI: 10.1056/NEJMc1610341State Regulations and Opioid Use among Disabled AdultsTo the Editor: Meara et al. (July 7 issue)1 con-clude that state laws such as those supporting prescription-drug monitoring programs (PDMPs) do not reduce hazardous opioid use or nonfatal overdose. These conclusions may cause clinicians and policymakers to discount the value of PDMPs. In addition, the findings of the study diverge from those of other recent studies assessing the effect of PDMPs.2-4 Patrick et al., using a more rigorous design to account for the specific features of PDMPs, found that these programs were associ-ated with declines in deaths from opioid over-dose.3 Bao et al., using a nationally representative sample — not only Medicare beneficiaries with disabilities — found a 30% decline in the prescrib-ing of Schedule II opioids after the implementation of PDMPs.4 The decision by Meara et al. to include multiple laws regarding controlled substances in a single analysis presupposes that each law within a category is identical. Categorizing laws as en-acted or not enacted ignores heterogeneity across laws of the same type. It is the components of a law and the implementation and enforcement of those components that matter. The null findings of the study may be a by-product of these meth-odologic choices. Additional investigation is need-ed to further evaluate the effects of PDMPs and other state-level interventions.The New England Journal of Medicine Downloaded from nejm.org at J H QUILLEN COLL OF MEDICINE on May 14, 2018. For personal use only. No other uses without permission.  Copyright © 2016 Massachusetts Medical Society. All rights reserved. 

Olanzapine for Chemotherapy-Induced Nausea and Vomiting

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Olanzapine for Chemotherapy-Induced Nausea and Vomiting

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