Chemotherapy-Induced Nausea and Vomiting: Time for More Emphasis on Nausea?

Abstract

Despite advances in antiemetic therapy, chemotherapyinduced nausea and vomiting (CINV) remains the most feared and expected side effect of chemotherapy [1]. Optimization of antiemetic therapy is important because CINV can lead to reduced quality of life, increased use of health care resources, and compromised treatment adherence. The combination of anthracycline and cyclophosphamide is used extensively in breast cancer patients and traditionally has been classified as being moderately emetogenic [2]. However, in 2011, the American Society of Clinical Oncology reclassified the combination of an anthracycline with cyclophosphamide as highly emetogenic, given its propensity to induce CINV, particularly nausea, in breast cancer patients [3]. Since then, local [4], national [3, 5], and international [6] antiemetic guidelines have emphasized the use of aprepitant in combination with 5-hydroxytryptamine-3 (5-HT3) antagonists and corticosteroids in this population. Not surprisingly, aprepitant-containing regimens have become the standard recommendation at many institutions, and aprepitant use has soared. Has this optimism from both patients and physicians significantly improved patient care?Despite the significant improvements in CINV reported in the aprepitant trials, control of CINV-and nausea in particular-remains suboptimal in patients receiving anthracycline and cyclophosphamide-based regimens [7,8]. In the nontrial setting, ∼58%-71% of patients will have nausea and/or vomiting despite "optimal" antiemetic prescribing (C. Hernandez-Torres, personal communication) [9]. What is the cause of this discrepancy? It is likely a combination of factors including health care staff underestimating the incidence of CINV [10], suboptimal adherence to antiemetic guidelines [9], lack of an optimal antiemetic regimen [11], clinical trials overestimating the benefit of antiemetics [7], and, quite simply, current trial endpoints that do not fully reflect patient experience. We feel this is an opportune moment to review the evidence to illustrate how antiemetic recommendations have evolved andtoraise ongoing issues and controversies in the management of CINV, especially in the breast cancer population.As all oncologists are aware, there has been significant progress in CINV control. Historically, antiemetic regimens were developed using cisplatin (.50 mg/m 2 ) as the benchmark because it causes CINV in almost all patients not receiving antiemetic prophylaxis. Based on the proposed pathophysiology of CINV, control of emesis has also been divided into acute (0-24 hours), delayed (.24-120 hours), and overall (0-120 hours) periods following chemotherapy [12], with antiemetic combinations being specifically chosen depending on their efficacy during these different time points. Following the results from antiemetic trials for patients receiving cisplatin-based chemotherapy (Table 1), most current antiemetic guidelines recommend a three-drug regimen consisting of aprepitant (days 1-3), 5-HT3 receptor antagonist (day 1), and dexamethasone (d...

Olanzapine versus fosaprepitant for the prevention of concurrent chemotherapy radiotherapy-induced nausea and vomiting

“…24,25 Two reviews on the prevention of chemotherapy-induced nausea concluded that NK-1 receptor antagonists are not efective in controlling nausea. 10,26 Te data from the currently reported trial and the others, noted above, support National Comprehensive Cancer Network guidelines, which list the olanzapine, palonosetron, and dexamethasone regimen as an optional frst-line therapy for the prevention of CINV in patients receiving HEC and MEC. 27 Tere are economic benefts of olanzapine.…”

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting

“…Although these agents (aprepitant, fosaprepitant, netupitant, and rolapitant) significantly controlled early and later emesis in patients receiving moderately or highly emetogenic chemotherapy they appear to have been less effective in controlling nausea. [1][2][3][4][5][6][7]18 In our study, patients who received olanzapine had more drowsiness on day 2 than at baseline, but for the most part, this symptom abated on days 3, 4, and 5, despite continued administration of oral olanzapine on days 3 and 4, suggesting that the patients adapted to the sedative effect of olanzapine. Undesired increase in appetite was not seen in the current trial.…”

“…Chemotherapy-induced nausea and vomiting are associated with a significant deterioration in quality of life and are perceived by patients as major adverse effects of cancer treatment. 1 The use of 5-hydroxytryptamine type 3 (5-HT 3 ) receptor antagonists, 2 dexamethasone, 2 and neurokinin-1 (NK 1 ) receptor antagonists [3][4][5][6][7][8][9] has significantly improved the control of this troublesome side effect. International guidelines [10][11][12] recommend combinations of these agents to prevent chemotherapy-induced nausea and vomiting in patients receiving moderately or highly emetogenic chemotherapy.…”

“…Nonetheless, nausea remains a major problem for many patients. 1,2 Olanzapine is approved by the Food and Drug Administration (FDA) as an antipsychotic agent that blocks multiple neurotransmitters: dopamine at D 1 , D 2 , D 3 , and D 4 receptors; serotonin at 5-HT type 2a, 5-HT type 2c (5-HT 2c ), 5-HT 3 , and 5-HT type 6 receptors; catecholamines at alpha 1 -adrenergic receptors; acetylcholine at muscarinic receptors; and histamine at H 1 receptors in the central nervous system. 8,9,13 Side effects may include mild short-term sedation, [13][14][15] as well as weight gain and an increased risk of diabetes mellitus with prolonged use (>6 months).…”

NCCN Guidelines Insights: Antiemesis, Version 2.2017

“…9,11,12 Although vomiting can often be prevented or substantially decreased by using prophylactic antiemetic regimens, nausea is much harder to control. [13][14][15][16][17][18] The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis are intended to provide an overview of the treatment principles for preventing chemotherapy-induced (or RT-induced) N/V, and to provide recommendations for antiemetic prophylaxis according to the emetogenic potential of antitumor therapies. These NCCN Guidelines are updated at least once a year by a multidisciplinary panel of experts; the first guidelines were published in 1997.…”