The Clinical Problem of Chemotherapy-Induced

The Clinical Problem of Chemotherapy-Induced

The Clinical Problem of Chemotherapy-Induced Nausea and Vom
Published on Cancer Network (http://www.cancernetwork.com)
The Clinical Problem of Chemotherapy-Induced Nausea and
Vomiting
August 15, 2016 | Oncology Journal [1], Nausea and Vomiting [2]
By Bernardo Rapoport, MD [3]
Beyond the current recommendations for management of chemotherapy-induced nausea and
vomiting, recent research has shown significant improvement in emesis control with use of triplet
therapy using dexamethasone, an NK1 receptor antagonist, and a 5-HT3 receptor antagonist in
patients undergoing non–anthracycline-plus-cyclophosphamide-based moderately emetogenic
chemotherapy.
Over the past 2 decades, substantial advances have been made in the management of
chemotherapy-induced nausea and vomiting (CINV). This is primarily because of a deeper
understanding of the molecular and physiologic pathways critical to CINV. The discovery of the
5-hydroxytryptamine type 3 (5-HT3) receptor and the subsequent development of 5-HT3 receptor
antagonists (RAs) in the early 1990s represent significant progress in the treatment of the acute
phase of CINV, with early studies showing improved outcomes when standard antiemetic therapy
with dexamethasone was combined with the 5-HT3 RAs granisetron[1] or ondansetron.[2] Also, the
discovery of the role of neurokinin-1 receptor antagonists (NK1 RAs) in the pathogenesis of the
delayed phase of CINV have led to significant developments in the management of the emetogenic
complication of anticancer treatment. Building on the benefits demonstrated with dual therapy using
a corticosteroid plus a 5-HT3 RA, large phase III studies in the early 2000s showed further benefit
from triplet regimens comprising the NK1 RA aprepitant given with dexamethasone plus the 5-HT3
RA ondansetron.[3,4] In their thorough review in this issue of ONCOLOGY, Drs. Nasir and
Schwartzberg describe the evolution and optimization of treatment regimens for CINV, highlighting
treatment-related, patient-related, and protocol-related factors that influence their effectiveness.[5]
As the authors note, although vomiting is fairly well managed with currently available antiemetic
regimens, chemotherapy-induced nausea remains an unmet medical need, with oncology physicians
and nurses often underestimating the magnitude of this clinical problem.[6] Despite the proper
implementation of pharmacologic and nonpharmacologic methods of prevention, nausea remains a
clinically significant side effect both for patients undergoing highly emetogenic chemotherapy (HEC)
and those undergoing moderately emetogenic chemotherapy (MEC).[7] For many patients, nausea
can have a devastating impact on quality of life and the ability to adhere to their selected
chemotherapy treatment regimen.
Olanzapine is a promising agent for the management of chemotherapy-induced nausea. It is an
antipsychotic thienobenzodiazepine whose antiemetic properties derive from its ability to target a
variety of receptor types involved in CINV pathogenesis. These include dopaminergic receptors (D1,
D2, D3, D4); serotonergic receptors (5-HT3 plus 5-HT receptor types 2A, 2C, and 6); and adrenergic
(A1), histaminergic (H1), and muscarinic (M1, M2, M3, M4) receptors. Olanzapine has been shown to
be beneficial in controlling CINV,[8-10] and may be particularly useful in the management of
breakthrough CINV.[11]
Current Practice Guidelines and Recent Developments in the Management
of CINV
As Drs. Nasir and Schwartzberg describe in detail, the NK1 RAs aprepitant, fosaprepitant, netupitant,
and rolapitant enhance the effectiveness of the antiemetic combination of a corticosteroid and a
5-HT3 RA (ondansetron, granisetron, and palonosetron) in controlling both the acute and delayed
phases of CINV. The Multinational Association of Supportive Care in Cancer/European Society for
Medical Oncology,[12] the National Comprehensive Cancer Network,[13] and the American Society
of Clinical Oncology[14,15] have developed evidence-based guidelines for use of regimens
incorporating these agents in the care of patients at risk of CINV. Because of the benefits reported in
large randomized controlled trials, current guidelines recommend triplet therapy (an NK1 RA in
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The Clinical Problem of Chemotherapy-Induced Nausea and Vom
Published on Cancer Network (http://www.cancernetwork.com)
combination with a 5-HT3 RA and dexamethasone) as the preferred treatment for preventing CINV
associated with anthracycline-plus-cyclophosphamide (AC)-based HEC and MEC.
Beyond the current recommendations for management of CINV, recent research has shown
significant improvement in emesis control with use of triplet therapy using dexamethasone, an NK1
RA, and a 5-HT3 RA in patients undergoing non–AC-based MEC (particularly for carboplatin-based
treatments).[16,17] Additionally, the use of an NK1 RA was associated with an improvement in CINV
control in patients undergoing high-dose chemotherapy with stem cell support,[18-20] as well as
patients undergoing multiple-day chemotherapy treatments.[21] These developments will be
incorporated into clinical antiemetic guidelines by MASCC/ESMO, and will be available in late 2016 or
2017. As Drs. Nasir and Schwartzberg emphasize, adherence by healthcare providers to the current
guidelines for management of CINV, along with consideration of relevant patient-specific and
treatment-specific factors, is essential to the “best practice” care of cancer patients in this
challenging clinical setting.
Financial Disclosure: Dr. Rapoport has received research funding from Merck and Tesaro, and
consultant fees from Heron Therapeutics, Merck, and Tesaro.
Oncology (Williston Park). 30(8):763–764.
References:
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a randomised, active-controlled, double-blind, phase 3 trial. Lancet Oncol. 2015;16:1071-8.
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Cancer. 2009;45:1184-7.
Source URL:
http://www.cancernetwork.com/oncology-journal/clinical-problem-chemotherapy-induced-nausea-and
-vomiting
Links:
[1] http://www.cancernetwork.com/oncology-journal
[2] http://www.cancernetwork.com/nausea-and-vomiting
[3] http://www.cancernetwork.com/authors/bernardo-rapoport-md
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