Aprepitant and Fosaprepitant: A 10-Year Review of Efficacy and Safety

Abstract

Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event associated with anticancer treatment that can have a significant adverse impact on patient health-related quality of life and that can potentially undermine the effectiveness of chemotherapy. Traditional regimens to prevent CINV generally involved a combination of a corticosteroid plus a 5-hydroxytryptamine (5HT 3 ) receptor antagonist (RA). In the past 10 years, antiemetic treatment has greatly advanced with the availability of the neurokinin-1 receptor antagonist (NK 1 RA) aprepitant and its prodrug fosaprepitant. NK 1 RAs have a different mechanism of action in CINV than corticosteroids and 5HT 3 RAs, thus their use can complement traditional antiemetic drugs and can enhance control of CINV.This review examined accumulated data regarding the safety and efficacy of aprepitant and fosaprepitant over the decade since the first regulatory approval. Data from key studies of aprepitant and fosaprepitant in the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy were explored, as were recommendations in currently available guidelines for their use. In addition, their use as antiemetic therapy in special patient populations was highlighted. Future perspectives on potential uses of aprepitant and fosaprepitant for indications other than CINV are presented. The Oncologist 2015; 20:450-458 Implications for Practice: Aprepitant (and its prodrug fosaprepitant) is a neurokinin-1 receptor antagonist approved more than a decade ago for the prevention of chemotherapy-induced nausea and vomiting (CINV). Its alternative mechanism of action complements traditional antiemetic drugs, enhancing control of CINV.This review examined safety and efficacy data for aprepitant and fosaprepitant accumulated since the first regulatory approval and explores recommendations in current guidelines for their use. The review serves as a useful reminder for the practitioner that aprepitant and fosaprepitant are valuable additions to the therapeutic armamentarium for the prevention of CINV. Future perspectives on potential uses of aprepitant and fosaprepitant for indications other than CINV are discussed.

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).…”

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

“…Tis is in contrast to previous CINV prevention studies that have used "no signifcant nausea (<2.5 on a scale of 0-10)" as a secondary endpoint. 2,[4][5][6]10 Te "no nausea" measure seems to be an important objective assessment of the status of patients in the postchemotherapy period, possibly equally or more important than "complete remission," which has been used as the primary endpoint in most clinical trials. "No nausea" should be strongly considered for use as a primary endpoint in future clinical trials.…”

“…1 Tere have been signifcant improvements in recent years in the control of chemotherapy-induced emesis with the use of the 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, 2,3 dexamethasone, 2,3 the neurokinin-1(NK-1) receptor antagonists, [4][5][6] and olanzapine, an antipsychotic that blocks multiple neurotransmitters in the central nervous system. [7][8][9] Chemotherapy-induced nausea, however, has not been as well controlled and remains a signifcant clinical problem.…”