Chemotherapy induced nausea and vomiting

1. CHEMOTHERAPY INDUCED
NAUSEAAND VOMITUS
(CNIV)
Bambang Sudarmanto
Department of Child Health Medical Faculty
Diponegoro University
Kariadi Hospital Semarang

2. CHEMOTHERAPY INDUCED
NAUSEAAND VOMITUS
(CNIV)
Bambang Sudarmanto
Department of Child Health Medical Faculty
Diponegoro University
Kariadi Hospital Semarang

3. CINV: Current Problem
 CINV is still a clinical problem
 Do not fully understand the pathophysiology of
CINV (e.g. acute, delayed)
 Medical complications: dehydration, electrolyte
imbalance, risk of aspiration pneumonia
 Effective management of N + V is essential
 Treatment planning for chemotherapy induced
nausea and vomiting should include both
physiologic and economic consideration

4. Etiology of Nausea and Vomiting in
Patients with Cancer
Direct Treatment Related:
• chemotherapy
– - acute
– - delayed
– - anticipatory
– - breakthrough N/V
– - refractory N/V
• radiation therapy
• prophylactic antibiotics
Indirect Treatment Related:
• mucositis
• opiates
• anti-infectives
• gastroparesis
• infection
• hyperacidity
• anorexia
• diarrhea
• pain
• anxiety

5. Difinition
• Nausea :
The unpleasant sensation of the imminent need to
vomit, usually referred to the throat or epigastrium
; a sensation that may or may not ultimately lead
to the act of vomiting
• Vomiting:
Forceful oral expulsion of gastric contents
associated with contraction of the abdominal and
chest wall musculature

6. Categories of CINV
• Acute
- usually within 24 hours after administration of
chemotherapy
• Delayed
- any time after first 24 hours to 7 days post
chemotherapy

7. Acute CINV
• Starts within the first 24 hours after chemotherapy
administration
– Majority of chemotherapeutic agents induce emesis
approximately 1–3 hours following administration
• Most researched type of CINV
– Remains common despite dramatically improved
protection
.Ann Oncol 1998;9:811–819.

8. Delayed CINV
• Starts 24 hours or more after chemotherapy administration
• First defined with high doses of cisplatin but known to occur
with other chemotherapy agents
– Carboplatin
– Cyclophosphamide
– Doxorubicin
– Epirubicin
– Anthracyclines
• Mechanism not known; appears to differ from acute emesis
Cancer. Ann Oncol 1998;9:811–819.

9. Categories of CINV (cont’d)
• Anticipatory
most common after 3-4 cycles chemotherapy
• Breakthrough
require treatment with an additional
pharmacological agent
• Refractory
patient who have failed on both standard
and rescue medication

10. CINV: Classification
Anticipatory Acute Delayed
Chemo 16 - 24 hours

11. Mechanisms of Chemotherapy-Induced
Nausea and Vomiting (CINV)
• Central mechanism
– Chemotherapeutic agent activates the chemoreceptor
trigger zone (CTZ)
– Activated CTZ invokes release of various neurotransmitters,
which stimulate vomiting center
• Peripheral mechanism
– Chemotherapeutic agent causes irritation and damage to
gastrointestinal (GI) mucosa, resulting in the release of
neurotransmitters
– Activated receptors send signals to vomiting center via
vagal afferents
Berger AM et al. In: Cancer: Principles and Practice of Oncology. 6th ed. Lippincott
Williams & Wilkins; 2001:2869–2880.

12. Proposed Pathways for Chemotherapy-
Induced Nausea and Vomiting (CINV)
Increased afferent input to the
chemoreceptor trigger zone
and vomiting center
Chemotherapy
Cell damage
Higher CNS centers
Release of neuroactive
agents
Activation of vagus
and splanchnic nerves
Small
intestine
Chemoreceptor trigger
zone
Medulla
oblongata
Vomiting center
Adapted from Grunberg SM et al N Engl J Med 1993;329:1790–1796.

13. Cisplatin Biphasic Pattern of CINV
• Maximal emetic intensity seen within 24 hours postdose
• Distinct second phase seen, occurring on Days 2–5 postdose
Adapted from Tavorath R, Hesketh PJ Drugs 1996;52:639–648. © 1996. Used with permission from Adis International Limited.
Acute Delayed
Time (Days)

14. Pattern Of Emesis: Cisplatin vs
Cyclophosphamide/Carboplatin
Cisplatin
Cyclophosphamide/Carboplatin
0 1 2 3 4 5
Days
Martin. Oncology. 1996;53(suppl 1):26-31.

15. Predisposing factor/ risk
• Female > Male
• Age > 3 years
• Past history of CNIV
• History of motion sickness
• Emetogenic potential of drug
• Administration schedule of chemotherapy
Cancer, J. 2008; 4: 85-93

16. Definition of Risk for CINV
• Minimal: <10%
• Low:10-30%
• Moderate 30-90%
• High >90%
Oncologist 2007; 12; 1143-1150

17. How to manage children with CINV
• Pharmacological
• Non pharmacological

18. Pharmacologic Agents
• Corticosteroids
• Dopamine antagonists
• Serotonin (5-HT3) antagonists
• NK-1 receptor antagonists
• Cannabinoids

19. Nonpharmacologic Managemen of
CNIV
• electro acupuncture, acupressure, and
noninvasive electro stimulation.
• acustimulation
• and massage or aromatherapy
(Ezzo et al., 2006; Oncology Nursing Society, 2008).

20. Nonpharmacologic Managemen of
CNIV (con’t)
• muscle relaxation,
• music therapy,
• education,
• support, and
• ginger therapy,
(Oncology Nursing Society, 2008).

28. Pattern Of Emesis: Cisplatin vs
Cyclophosphamide/Carboplatin
Cisplatin
Cyclophosphamide/Carboplatin
0 1 2 3 4 5
Days
Martin. Oncology. 1996;53(suppl 1):26-31.

29. Gasteroenterology Nursing 28: 477
Serotonin pathways
Substance P
Post Chemotherapy Nausea and Vomiting

31. Mechanisms of Chemotherapy-Induced
Nausea and Vomiting (CINV)
• Central mechanism
– Chemotherapeutic agent activates the chemoreceptor
trigger zone (CTZ)
– Activated CTZ invokes release of various neurotransmitters,
which stimulate vomiting center
• Peripheral mechanism
– Chemotherapeutic agent causes irritation and damage to
gastrointestinal (GI) mucosa, resulting in the release of
neurotransmitters
– Activated receptors send signals to vomiting center via
vagal afferents
Berger AM et al. In: Cancer: Principles and Practice of Oncology. 6th ed. Lippincott
Williams & Wilkins; 2001:2869–2880.

33. Jumlah Pemakaian
Obat Anti Muntah Pasien Sitostatika Thun 2011
RSUP Dr. Kariadi Semarang
0.00
500.00
1,000.00
1,500.00
2,000.00
2,500.00
3,000.00
3,500.00
1 2 3 4 5 6 7 8 9 10 11 12
granisetron 1mg inj
granisetron 3mg inj
ramosetron inj
ramosetron tab
Ondansetron 4mg inj
Ondansetron 4mg tab
Ondansetron 8mg inj
Ondansetron 8mg tab
palonosetron inj

34. CINV: Emetogenic risk

35. CINV: Classification
Anticipatory Acute Delayed
Chemo 16 - 24 hours

39. Nonpharmacologic Management of
Chemotherapy-induced Nausea and
Vomiting
• electro acupuncture, acupressure, and
noninvasive electro stimulation.
• acustimulation
• and massage or aromatherapy
(Ezzo et al., 2006; Oncology Nursing Society, 2008).

40. Nonpharmacologic Management of
Chemotherapy-induced Nausea and
Vomiting (cont’d)
• muscle relaxation,
• music therapy,
• education,
• support, and
• ginger therapy,
(Oncology Nursing Society, 2008).

41. How Can We Improve the Value of Care in
CINV?
Value = Quality  Cost
 CR
 Nausea or Emesis  Functioning
 Side Effects
 Compliance or  Patient
Inconvenience
 Access to Care
• Direct
• Indirect

42. Vomiting Centre
(medulla)
Cerebral cortex
Anticipatory emesis
Smell
Sight
Thought
Vestibular
nucleiMotion
sickness
Pharynx & GIT
Chemo & radio therapy
Gastroenteritis
(vagus)
Chemoreceptor
Trigger Zone
(CTZ)
(Outside BBB)
Cancer chemotherapy
Opioids
Muscarinic, 5 HT3 &
Histaminic H1
5 HT3 receptors
Dopamine D2
5 HT3,,Opioid
Receptors
Muscarinic
Histaminic H1
Pathophysiology of Emesis

43. Mechanism of Nausea and Vomiting
• vomiting centre in reticular formation of
medulla
• activated by stimuli from:
– Chemoreceptor Trigger Zone (CTZ)
• area postrema, floor of the fourth ventricle
• outside blood-brain barrier (fenestrated venules)
– Upper GI tract & pharynx
– Vestibular apparatus
– Higher cortical centres

44. Cortex
CTZ
Vestibular
GI
VOMITING
CENTRE

45. Stimulus Area Receptors
Drugs,
Metabolic
Chemoreceptor
trigger zone
Motion,
Position
Vestibular
Visceral Organs
? Non-
specific
CNS
↑ ICP Cerebral cortex
D2 5HT
M H1
VOMITING
CENTRE
Effector
Organs
Dopamine Serotonin Histamine Muscarinic
CB1
Cannabinoid
CB1
D2
D2
5HT
5HT
H15HT
H1
H1
M
M

46. Indications of antiemetics
1- Chemotherapy-induced vomiting
2- Post irradiation vomiting
3- Postoperative vomiting
4- Vomiting of pregnancy
5- Motion sickness
Serotonin 5 HT3 Antagonists:
Dopamine D2 Antagonist:
Anticholinergics:
H1 Antihistaminics
Group of drugs used as antiemetics