Dr Melsew Abeje from bahir dar university

1. chemotherapy-induced nausea
and vomiting(CINV)
 Melsew.A.(R1).

2. Outlines
• Introduction
• Types of emesis
• Pathophysiology
• Predictive factors
• Prevention andtreatment.
• References

3. Introduction
 Patients with cancer may experience many
side effects while receiving chemotherapy
but few side effects are more feared than
nausea and vomiting
 In the past, nausea and vomiting were
inevitable side effects of chemotherapy and
forced up to 20% of patients to postpone or
refuse potentially curative treatment.

4. Cont..
 Nausea and vomiting are usually self-
limiting .
 Sometime they can have the
deleterious effects on nutritional status
and quality of life .

5. Cont..
• Many recently introduced therapeutic
antibodies and oral agents have less
potential to produce nausea and
vomiting.
• However, combination chemotherapy
continues to be the cornerstone of
treatment for many types of cancer.

6. Types of emesis
• Three distinct types of CINV :
 acute emesis
 delayed emesis
 anticipatory emesis

7. Cont..
Acute emesis :
 Occurs during the first 24 hours after
chemotherapy.
In the absence of effective
prophylaxis, it most commonly begins
within 1-2 hours of CT and usually
peaks in the first 4-6 hours.

8. Cont..
Delayed emesis
 occurs more than 24 hours after
chemotherapy is classified as delayed
 It is best characterized following
treatment with high-dose cisplatin .

9. Cont..
In the absence of antiemetic
prophylaxis, delayed emesis after
cisplatin peaks at approximately 48 to
72 hours after therapy, then gradually
subsides over the next 2-3 days.

10. Cont..
Anticipatory emesis
 Anticipatory emesis is a conditioned
response in patients who have
developed significant nausea and
vomiting during previous cycles of CT.

11. PATHOPHYSIOLOGY
 The pathophysiology of CINV is not
entirely understood; however, it is
thought to have many contributing
pathways.
 The central nervous system plays a
critical role in the physiology of
nausea and vomiting.

12. Cont..
 The existence of two distinct sites in
the brainstem believed to be critical for
the control of emesis:
vomiting center.
chemoreceptor trigger zone (CTZ)

13. Vomiting center
• It was also thought to be located
adjacent to the other structures
involved in the coordination of the
respiratory, vasomotor, and salivary
centers, and cranial nerves VIII and X

14. Cont..
 More recent studies have suggested
that it is actually not anatomically
discrete but the initiation of the
vomiting reflex is controlled by a
complex system of networks located in
the brainstem.

15. Area postrema (AP)
 Called a "chemoreceptor trigger zone“.
• It is located outside the blood-brain
barrier, is exposed to various noxious
agents borne in the blood or
cerebrospinal fluid.
 Located circumventricularly (at the caudal
end of the 4th ventricle)

18. Mechanisms

19. Neurotransmitters
 Although over 30 neurotransmitters
have been associated with the
peripheral and central nervous system
sites involved in CINV, three
neurotransmitters have the most
clinical relevance

20. Cont..
• Dopamine
• Serotonin (5-hydroxytryptamine)
• Substance P

21. Predictive factors
 There are multiple clinical factors that
are important in determining the
incidence and severity of
chemotherapy-induced nausea and
vomiting .
 These factors include the type of
chemotherapy administered, certain
patient characteristics, and the
antiemetic regimen used.

22. Cont..
DETERMINANTS OF CHEMOTHERAPY-INDUCED
NAUSEA AND VOMITING
•Chemotherapy
• Emetic potential of drug(s) used
• Dose
• Schedule of administration
• Route of administration
•Patient Characteristics
•.Age
• Gender
• Alcohol use
• Emesis control during prior chemotherapy
•History of motion sickness

23. Cont..
 The most important is:
 the intrinsic emetogenicity of the
chemotherapy agent
 mode of administration of CT
 CT agents were placed into four risk
categories in the absence of effective
antiemetic prophylaxis.

24. Cont..
 High — >90 percent risk of emesis
 Moderate — >30 to 90 percent risk of
emesis
 Low — 10 to 30 percent risk of emesis
 Minimal — <10 percent risk of emesis

25. Cont…
High risk (>90%) Acute emesis ++ Delayed emesis ++
Moderate risk (30–90%) Acute emesis ++ Delayed emesis +
Low risk (10–30%) Acute emesis + Delayed emesis –
Minimal risk (<10%) Acute emesis – Delayed emesis –

27. Emetogenic Potential of Commonly
Used Intravenous Antineoplastic Agents

28. Prevention and treatment
 The four categories of drugs with the
highest therapeutic index for the
management CINV include:
 type three 5-hydroxytryptamine (5-
HT3) receptor antagonists
the neurokinin-1 (NK1) receptor
antagonists aprepitant and fosaprepita
nt
 Glucocorticoids
Dopamine receptor antagonist

29. All first-generation 5-HT3
receptor antagonists
They have proven to be most effective
in the prevention of acute CINV
They are considered therapeutically
equivalent and are used
interchangeably
They have similar toxicity profiles
Oral formulations have similar
efficacy to intravenous formulations.

30. Palonosetron is a second-
generation 5-HT3 antagonist
Has a longer half-life of 40 hours
Has a higher binding affinity to the 5-
HT3 receptor.

31. Cont…
 Adverse effects are qualitatively
similar among agents and include:
headache
constipation
diarrhea
transiently increased hepatic
transaminase concentrations
transient electrocardiogram (ECG)
changes decreased cardiac rate

32. Glucocorticoids
Mechanism of action is unknown
probably
It may have multiple site of action
In the acute and delayed phase, it
increase the chance of complete
prevention of vomiting by 25% to 30%
versus placebo
With moderate to highly emetogenic
chemotherapy regimens,
corticosteroids are typically not used
alone

33. Cont…
Although no obvious differences in
efficacy have been demonstrated
among the corticosteroids,
dexamethasone is almost universally
used.
They consistently add to the effect of
other antiemetic agents when used in
combination presumably because of
their different mechanism of action

34. Dopamine-2 Receptor
Antagonists
 Metoclopramide is a D2 receptor
antagonist, and is a weak competitive
5-HT3 receptor antagonist at high
doses.
 Its activity against delayed-phase
symptoms is equivalent to that of
ondansetron.

35. Cont..
 The profile of adverse effects of potent
D2 receptor antagonists:
Dose-related sedation
Extrapyramidal reactions (EPRs).
Anticholinergic effects
 Gastrointestinal prokinetic effects may
be useful for patients who have
concomitant motility disorders or
gastroesophageal reflux disease.

36. Cont..
 Incidence of adverse effects also
correlates directly with the magnitude
of the dose and the frequency of
administration:
Sedation
EPRs
Anticholinergic effects

37. Other agents
 Other agents that have been used in
the treatment or prevention of CINV
include;
phenothiazines, butyrophenones, and
cannabinoids.
 These agents have a lower
therapeutic index than the 5-HT3
receptor antagonists, aprepitant , and
glucocorticoids for highly or
moderately emetogenic chemotherapy
regimens

38. Cont..
 Their use should be restricted to
patients who are intolerant of or
refractory to these first line agents.
 Phenothiazines could be used as an
alternative to single
agent dexamethasone for those
receiving chemotherapy with a low risk
of emesis, if a glucocorticoid is
contraindicated.

43. Olanzapine for the Prevention of
Chemotherapy-Induced Nausea and Vomiting
July 14, 2016

46. Ondansetrone compared with dexa and
metoclopramide

52. References
 uptodate 21.6
Abeloffs clinical oncology
5th edition
Devita 8th edition
NEnGLJ med 374;14 nejm.org
April 7, 2016.
NCCN guide line version
2,2016