Fosaprepitant dimeglumine for the management of chemotherapy-induced nausea and vomiting: patient selection and perspectives

Figures & data

Table 1 Risk factors for CINV

Risk factors	Change in risk
Sex	Greater risk in females
Age	Lower incidence at <6 or >50 years
Alcohol consumption	Lower incidence in individuals consuming >10 alcohol units/week
Motion sickness	Prior history leads to greater risk
Pregnancy-induced emesis	Prior history leads to greater risk
Anxiety	High anxiety levels correlated with greater risk
Previous cycles of chemotherapy	Poorly controlled nausea and vomiting in previous cycles increases the likelihood of CINV and anticipatory nausea and vomiting

Notes: Republished with permission of AlphaMed Press, from Schnell FM. Chemotherapy-induced nausea and vomiting: the importance of acute antiemetic control. Oncologist. 2003;8(2):187–198; Copyright © 2003 AlphaMed Press; permission conveyed through Copyright Clearance Center, Inc.¹⁵

Abbreviations: CINV, chemotherapy-induced nausea and vomiting.

Table 2 Emetogenic levels of antineoplastic drugs

Minimal risk	Low risk	Moderate risk	High risk
Bevacizumab	Bortezomib	Carboplatin	Carmustine
Bleomycin	Cetuximab	Cyclophosphamide (≤1.5 g/m^2)	Cisplatin
Busulfan	Cytarabine (≤100 mg/m^2)	Cytarabine (>1 g/m^2)	Cyclophosphamide (>1.5 g/m^2)
Cladribine	Docetaxel	Daunorubicin	Dacarbazine
Fludarabine	Etoposide	Epirubicin	Mechlorethamine
Vinblastine	Fluorouracil	Idarubicin	Streptozocin
Vincristine	Gemcitabine	Ifosfamide
Vinorelbine	Ixabepilone	Irinotecan
	Lapatinib	Oxaliplatin
	Methotrexate
	Mitomycin
	Mitoxantrone
	Paclitaxel
	Pemetrexed
	Temsirolimus
	Topotecan
	Trastuzumab

Notes: From N Engl J Med; Hesketh PJ; Chemotherapy-induced nausea and vomiting; 358(23);2482–2494; Copyright © 2008 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.¹⁸

Table 3 Drug interactions of (Fos)aprepitant: review of literature and implications for clinical practice

Drug class	Major CYP450 pathway	Comments
Antineoplastics	Alkylating agents (CYP3A4 inhibition)  Cyclophosphamide  Ifosphamide	Slight increase in blood levels but no clinically significant impact (cyclophosphamide); increases neurotoxicity with ifosphamide
	Topoisomerase inhibitor (CYP3A4 inhibition)  Etoposide	Theoretical increase in blood levels that requires close clinical monitoring
	Microtubule inhibitor (CYP3A4 inhibition)  Docetaxel/paclitaxel	Theoretical increase in blood levels that requires close clinical monitoring
	Tyrosine kinase inhibitor (CYP3A4 inhibition) Crizotinib Erlotinib	Theoretical increase in blood levels; increased levels noted with Erlotinib that can potentiate antitumor response
Opioids	Opioids (CYP3A4 inhibition)  Oxycodone  Fentanyl  Hydrocodone Methadone	Monitor for respiratory depression and sedation
Anticoagulants	Warfarin (CYP2C9 induction)	Decreases INR that requires close monitoring and increased dosing
	Apixiban/rivaroxaban (CYP3A4 inhibition)	Potential to increase bleeding that requires close monitoring

Notes: Adapted from Dushenkoy A, Kalabalik J, Carbone A, Jungsuwadee P. J Oncol Pharm Pract. Drug interactions with aprepitant or fosaprepitant: review of literature and implications for clinical practice. Epub February 25, 2016. Copyright © 2016 by SAGE Publications. Reprinted by permission of SAGE Publications, Ltd.²²

Abbreviation: INR, international normalized ratio.

Table 4 Summary of clinical trials on fosaprepitant

Study, location	Design	Study patients	Type of malignancy	Sample size	Intervention		Study period	Outcome	Fosaprepitant regimen
					Fosaprepitant regimen	Comparison			Result	Conclusion
Grunberg et al,^Citation23 Canada	Randomized double-blind noninferiority	Cisplatin based (≥70 mg/m^2) – HEC	Lung, GI, GU, breast	2,322	F + O + D	A + O + D	1–5 days post-chemo	CR*	71.9% vs 72.3%; (95% CI −4.1 to 3.3)	Noninferior
Saito et al,^Citation25 Japan	Randomized double-blind placebo-controlled superiority	Cisplatin based (≥70 mg/m^2) – HEC	Lung, GI, GU, head and neck	347	F + G + D	Pl + G + D	1–5 days post-chemo	CR*	64% vs 47%; P=0.001	Superior
Ando et al,^Citation24 Japan	Randomized open-label controlled noninferiority	Patients on cisplatin containing (≥60 mg/m^2) – HEC	Lung, GI, head and neck	93	F + P/G/Az + D	A + P/G/Az + D	1–7 days post-chemo	CR*	82.2% vs 85.4%; P=0.90	Noninferior
Weinstein et al,^Citation26 International	Randomized double-blind Phase III superiority	Non-AC chemotherapy regimen – MEC	Lung, GI, gynecologic, breast, head and neck	1,015	F + O + D	Pl + O + D	0–120 hours post-chemo	CR*	77.1% vs 66.9%; P<0.001	Superior
Nishimura et al,^Citation27 Japan	Randomized open-label controlled Phase III	Patients on oxaliplatin based – MEC	Colorectal	413	F/A + O + D	O + D	1–7 days post-chemo	No emesis	95.7% vs 83.6%; P<0.0001	Superior
Kitayama et al,^Citation28 Japan	crossover	Patients on (oxaliplatin/irinotecan based) – MEC	Colorectal, breast	35	F + G + D	P + D	1–5 days post-chemo	CR*	69% vs 74%; P=0.56	Noninferior

Note:

* No vomiting or use of rescue anti-emetics.

Abbreviations: A, aprepitant; AC, adriamycin + cyclophosphamide; Az, azasetron; CI, confidence interval; CR, complete response; D, dexamethasone; F, fosaprepitant; G, granisetron; GI, gastrointestinal; GU, genitourinary; HEC, highly emetogenic chemotherapy; MEC, moderately emetogenic chemotherapy; O, ondansetron; P, palonosetron; Pl, placebo; chemo, chemotherapy.

Table 5 Clinical practice guidelines in the management of chemotherapy-induced nausea and vomiting

	High emetic risk	Moderate emetic risk	Low emetic risk
ASCOa	NK-1 antagonist (aprepitant/fosaprepitant) + 5-HT3 antagonist (granisetron/ondansetron/palonosetron/dolasetron/tropisetron/ramosetron) + dexamethasone	Palonosetron + dexamethasone	Dexamethasone
NCCN^®,b	NK-1 antagonist (aprepitant/fosaprepitant/rolapitant) + 5-HT3 antagonist (dolasetron/ondansetron/granisetron/palonosetron) + dexamethasone or Netupitant + palonosetron + dexamethasone or Olanzapine + palonosetron + dexamethasone	5-HT3 antagonist (dolasetron/ondansetron/granisetron/palonosetron) + dexamethasone with or without NK-1 antagonist (aprepitant/fosaprepitant/rolapitant) or netupitant + palonosetron + dexamethasone or olanzapine + palonosetron + dexamethasone	Dexamethasone or prochlorperazine or 5-HT3 antagonist(dolasetron/granisetron/ondansetron)
ESMO/MASCCc	NK-1 antagonist (aprepitant/fosaprepitant) + 5-HT3 antagonist + dexamethasone	AC regimen NK-1 antagonist (aprepitant/fosaprepitant) + 5-HT3 antagonist + dexamethasone Non-AC regimen palonosetron + dexamethasone	Dexamethasone or 5-HT3 antagonist or Dopamine antagonist

Notes:

a Data from Basch et al.⁶

b Referenced from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for NCCN Guidelines for Antiemesis V.2.2016. © National Comprehensive Cancer Network, Inc 2016. All rights reserved. Accessed March 31, 2016. To view the most recent and complete version of the guideline, go online to www.nccn.org. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, NCCN GUIDELINES^®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.³⁵

c Adapted from Roila F, Herrstedt J, Aapro M, et al. Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Annals of Oncology. 2010;21(Suppl 5):v232–v243. By permission of Oxford University Press on behalf of the European Society for Medical Oncology. This image/content is not covered by the terms of the Creative Commons license of this publication. For permission to reuse, please contact the rights holder. Copyright © 2010, Oxford University Press.³⁶

Abbreviations: ASCO, American Society of Clinical Oncology; NCCN, National Comprehensive Cancer Network^®; ESMO, European Society of Medical Oncology; MASCC, Multinational Association of Supportive Care in Cancer; NK-1, neurokinin-1; 5-HT3, 5-hydroxytriptamine/serotonin; AC, anthracycline/cyclophosphamide.

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