ASCO guidelines

1. Dr. Varshu Goel
First Year Post-Graduate Resident
Department of Radiotherapy
Maulana Azad Medical College, Delhi

2. 2

3. 3
Physiology

4. 4
Mechanism of Action

5. Mechanism of Action
• Serotonin : free radicals increase serotonin production by
enterochromaffin cells in GIT(vagal sensory nerve input); also
act directly on CTZ
• Substance P/NK1 : central acting
• Dexamethasone: central action, by decreasing production of
prostaglandin and serotonin
• Metoclopramide: antagonist activity at D2 receptors in the
chemoreceptor trigger zone and increased gastric emptying
(prokinetic); and at higher doses, 5-HT3 antagonist activity
centrally
• Olanzapine : atypical antipsychotic agent; has ability to block
many different receptors; targets dopaminergic (D1, D2, D3,
D4), serotonergic (5-HT2A, 5-HT2C, 5-HT3, 5-HT6) and others 5
NCCN, 2017

6. Classification of CINV
6
CINV type Clinical features
Anticipatory • Feeling of nausea or vomiting prior to next chemotherapy
• Conditioned response
• Occurs in 25–50% of patients
Acute • Occurs and resolves within 24 hours of chemotherapy
• Generally peaks within 5–6 hours
Delayed • Occurs 1–6 days after chemotherapy
• Common with administration of cisplatin, carboplatin,
cyclophosphamide, and doxorubicin
Breakthrough • Occurs despite prophylactic treatment
• Requires rescue therapy
• Can be acute or delayed
Refractory • Occurs during chemotherapy cycle after prophylaxis and/or rescue
therapy has failed in earlier cycles
NCCN, 2017

7. Nausea Vomiting
1 Loss of appetite without
alteration in eating habits
1 - 2 episodes (separated by 5
minutes) in 24 hours
2 Oral intake decreased without
significant weight loss,
dehydration or malnutrition
3 - 5 episodes (separated by 5
minutes) in 24 hours
3 Inadequate oral caloric or fluid
intake; tube feeding, TPN, or
hospitalization indicated
6 episodes (separated by 5
minutes) in 24 hours;
tube feeding, TPN or hospitalization
indicated
4 Life-threatening consequences;
urgent intervention indicated
5 Death
Grades
7
CTCAE, 4.03

8. Emetic Risk
• The emetic risk of antineoplastic mediations was classified by using
four levels based on the likelihood of emesis in the absence of
antiemetic prophylaxis:
• high (>90%)
• moderate (30% to 90%)
• low (10% to 30%)
• minimal (<10%)
• Patient-related risk factors
• Younger age
• Female gender
• Susceptibility to motion sickness
• No history of alcohol
• Poor control with prior chemotherapy
• Anxiety
• Medications such as digitalis derivatives, opioids, NSAIDs, and
antibiotics
• Uremia
• Increased intracranial pressure
• Gastrointestinal abnormalities: obstruction, ascites, gastroparesis.
8
NCCN, 2017

9. • Emetic Risk of Single Intravenous Antineoplastic Agents in Adults
9
• High (>90%) • Moderate (30%-
90%)
• Low (10%-30%) • Minimal
(<10%)
• Anthracycline/
cyclophosphami
de combination
• Carmustine
• Cisplatin
• Cyclophosphami
de  1,500
mg/m2
• Dacarbazine
• Mechlorethamin
e
• Streptozocin
• Alemtuzumab
• Bendamustine
• Carboplatin
• Clofarabine
• Cyclophosphami
de < 1,500
mg/m2
• Cytarabine >
1,000 mg/m2
• Daunorubicin
• Doxorubicin
• Epirubicin
• Idarubicin
• Ifosfamide
• Irinotecan
• Oxaliplatin
• Romidepsin
• Temozolomide
• Thiotepa
• Aflibercept
• Belinostat
• Bortezomib
• Brentuximab
• Cetuximab
• Cytarabine  1,000 mg/m2
• Docetaxel
• Etoposide
• Fluorouracil
• Gemcitabine
• Methotrexate
• Mitomycin
• Nab-paclitaxel
• Paclitaxel
• Pemetrexed
• Pegylated liposomal
doxorubicin
• Pertuzumab
• Topotecan
• Trastuzumab-emtansine
• Bevacizumab
• Bleomycin
• Busulfan
• Fludarabine
• Nivolumab
• Pembrolizumab
• Pralatrexate
• Ramucirumab
• Rituximab
• Trastuzumab
• Vinblastine
• Vincristine
• Vinorelbine

10. • Emetic Risk of Oral Antineoplastic Agents in Adults
10
• High (>90%) • Moderate (30%-
90%)
• Low (10%-30%) • Minimal (<10%)
• Hexa-
methylmelam
ine
• Procarbazine
• Bosutinib
• Cabozantinib
• Ceritinib
• Crizotinib
• Cyclophosphamide
• Imatinib
• Lenvatinib
• TAS-102
(trifluridine-tipiracil)
• Temozolomide
• Vinorelbine
• Afatinib
• Alectinib
• Axatinib
• Capecitabine
• Etoposide
• Lapatinib
• Lenalidomide
• Olaparib
• Nilotinib
• Palbociclib
• Pazopanib
• Ponatinib
• Panobinostat
• Regorafenib
• Sonidegib
• Sunitinib
• Tegafur-uracil
• Thalidomide
• Vorinostat
• Chlorambucil
• Erlotinib
• Gefitinib
• Hydroxyurea
• Melphalan
• Methotrexate
• Pomalidomide
• Ruxolitinib
• Sorafenib
• 6-Thioguanine
• Vemurafenib
• Vismodegib

12. • Antineoplastic agent-induced nausea and vomiting in adults
12
Previous 2011 Current 2017
Optimal treatment to
prevent nausea and
vomiting from high
emetic risk
antineoplastic agents
in adults who receive
single-day
antineoplastic agent
therapy
three-drug combination of a NK
1 receptor antagonist, a 5-HT3
receptor antagonist, and
dexamethasone.
The oral combination of
netupitant and palonosetron
(NEPA) plus dexamethasone is
an additional treatment option
in this setting.
 Adult patients treated with
cisplatin and other high-emetic-
risk single agents who receive
single-day antineoplastic agent
therapy should be offered a four-
drug combination of :
• NK1 receptor antagonist
• 5-HT3 receptor antagonist
• dexamethasone, and
• olanzapine
Dexamethasone and olanzapine
should be continued on days 2 to 4
 Adult patients treated with 4- or
5-day cisplatin regimens should be
offered a three drug combination
of an NK1 receptor antagonist, a
5-HT3 receptor antagonist, and
dexamethasone

13. • Antineoplastic agent-induced nausea and vomiting in adults
13
Previous 2011 Current 2017
High emetic risk three-drug combination of a NK
1 receptor antagonist, a 5-HT3
receptor antagonist, and
dexamethasone.
The oral combination of
netupitant and palonosetron
(NEPA) plus dexamethasone is
an additional treatment option
in this setting.
Adult patients treated with an
anthracycline combined with
cyclophosphamide (AC) should be
offered a four-drug combination of :
• NK1 receptor antagonist
• 5-HT3 receptor antagonist
• dexamethasone, and
• olanzapine.
Olanzapine should be continued on
days 2 to 4

14. 14
Previous Current
Optimal treatment
to prevent nausea
and vomiting from
moderate emetic
risk antineoplastic
agents in adults who
receive single-day
antineoplastic agent
therapy
two-drug combination of
palonosetron (day 1 only) and
dexamethasone (days 1-3) is
recommended for patients
receiving moderately
emetogenic chemotherapy.
If palonosetron is not available,
clinicians may substitute a first
generation 5-HT3 receptor
antagonist, preferably
granisetron or ondansetron.
Limited evidence also supports
adding aprepitant to the
combination. Should clinicians
opt to add aprepitant in patients
receiving moderate
risk chemotherapy, any one of
the 5-HT3 receptor antagonists
is appropriate.
 Adult patients treated with
carboplatin AUC ≥ 4 mg/mL/min
should be offered a three-drug
combination of NK1 receptor
antagonist, 5-HT3 receptor
antagonist, and dexamethasone
 Adult patients treated with
moderate emetic risk
antineoplastic agents (excluding
carboplatin AUC ≥ 4 mg/mL/min)
should be offered a two-drug
combination of a 5-HT3 receptor
antagonist (day 1) and
dexamethasone (day 1)
 Adult patients treated with
cyclophosphamide, doxorubicin,
oxaliplatin and other moderate
emetic- risk antineoplastic agents
known to cause delayed nausea
and vomiting may be offered
dexamethasone on days 2 to 3

15. 15
Previous Current
optimal treatment
to prevent nausea
and vomiting from
low emetic-risk
antineoplastic
agents in adults who
receive single-day
antineoplastic agent
therapy
A single 8 mg dose of
dexamethasone before
chemotherapy is suggested.
Adult patients treated with low-
emetic-risk antineoplastic agents
should be offered a single dose of a
5-HT3 receptor antagonist or a single
8-mg dose of dexamethasone before
antineoplastic treatment
Minimal emetic
risk
No antiemetic should be
administered routinely before or
after chemotherapy.
Adult patients treated with minimal
emetic risk antineoplastic agents
should not be offered routine
antiemetic prophylaxis
Antineoplastic
combinations
Patients should be administered
antiemetics appropriate for the
component chemotherapeutic
(antineoplastic) agent of
greatest emetic risk.
Adults patients treated with
antineoplastic combinations should
be offered antiemetics appropriate
for the component antineoplastic
agent of greatest emetic risk.

16. 16
Previous Current
Adjunctive drugs Lorazepam or diphenhydramine
are useful adjuncts to antiemetic
drugs, but are not
recommended as single agent
anti-emetics.
Lorazepam is a useful adjunct to
antiemetic drugs, but is not
recommended as a single agent
antiemetic.
Cannabinoids Not addressed Evidence remains insufficient for a
recommendation regarding medical
marijuana for the prevention of
nausea and vomiting in patients with
cancer receiving chemotherapy or
radiation therapy.
Evidence is also insufficient for a
recommendation regarding the use
of medical marijuana in place of the
tested and US Food and Drug
Administration approved
cannabinoids : dronabinol and
nabilone

17. 17
Previous Current
Complementary
therapy
No published data Evidence remains insufficient for a
recommendation for or against the use of
ginger, acupuncture/acupressure, and
other complementary or alternative
therapies for the prevention of nausea and
vomiting in patients with cancer.
High-dose
chemotherapy with
stem cell or bone
marrow transplant
A 5-HT3 receptor
antagonist combined with
dexamethasone is
suggested.
Aprepitant should be
considered, although
evidence to support its use
is limited.
Adult patients treated with high-dose
chemotherapy and stem-cell or bone
marrow transplantation should be offered
a three-drug combination of an NK1
receptor antagonist, 5-HT3 receptor
antagonist, and dexamethasone

18. 18
Previous Current
Multi-day
antineoplastic
therapy
antiemetics appropriate for the
emetogenic risk class of the
chemotherapy be administered
for each day of the
chemotherapy and for two days
after, if appropriate.
Adult patients treated with multi-day
antineoplastic agents should be
offered anti-emetics before
treatment that are appropriate for
the emetic risk of the antineoplastic
agent given on each day of the
antineoplastic treatment and for 2
days after completion of the
antineoplastic regimen
Adult patients treated with 4- or 5-
day cisplatin regimens should be
offered a three - drug combination of
an NK1 receptor antagonist, a 5-HT3
receptor antagonist, and
dexamethasone

19. 19
Previous Current
For adults who
experience nausea
and vomiting
secondary to
antineoplastic agent
therapy despite
optimal prophylaxis
(breakthrough)
Re-evaluate emetic risk, disease
status, concurrent illnesses, and
medications
Ascertain that the best regimen
is being administered for the
emetic risk
Consider adding lorazepam or
alprazolam to the regimen
Consider adding olanzapine to
the regimen or substituting
high-dose intravenous
metoclopramide
for the 5-HT3 receptor
antagonist or adding a
dopamine antagonist to the
regimen.
Re-evaluate emetic risk, disease
status, concurrent illnesses, and
medications and ascertain that the
best regimen is being administered
for the emetic risk
Adult patients who experience
nausea or vomiting despite optimal
prophylaxis, and who did not receive
olanzapine prophylactically, should
be offered olanzapine in addition to
continuing the standard antiemetic
regimen
Adult patients who experience
nausea or vomiting despite optimal
prophylaxis, and who have already
received olanzapine, may be offered
a drug of a different class (e.g., an
NK1 receptor antagonist, lorazepam
or alprazolam, a dopamine receptor
antagonist, dronabinol, or nabilone)
in addition to continuing the
standard antiemetic regimen

20. 20
Previous Current
Anticipatory
nausea and
vomiting
Use of the most active
antiemetic regimens appropriate
for the chemotherapy being
administered to prevent acute
or delayed emesis is suggested.
Such regimens should be used
with initial chemotherapy, rather
than assessing the patient’s
emetic response with less
effective treatment.
If anticipatory emesis occurs,
behavioral therapy with
systematic desensitization is
effective and suggested.
All patients should receive the most
active antiemetic regimen
appropriate for the antineoplastic
agents being administered.
Clinicians should use such regimens
with initial antineoplastic treatment,
rather than assessing the patient’s
emetic response with less effective
antiemetic treatment.
If a patient experiences anticipatory
emesis, clinicians may offer
behavioral therapy with systematic
desensitization

21. 21

22. 22
Previous Current
High emetic risk
radiation therapy
all patients should receive a 5-
HT3 receptor antagonist before
each fraction and for at least 24
hours after completion of
radiotherapy. Patients should
also receive a five day course of
dexamethasone before fractions
1-5
two-drug combination of a 5-HT3
receptor antagonist and
dexamethasone before each fraction
and on the day after each fraction, if
radiation therapy is not planned for
that day
Moderate emetic
risk radiation
therapy
a 5-HT3 receptor antagonist
before each fraction for the
entire course of radiotherapy.
Patients may be offered a short
course (fractions 1-5) of
dexamethasone before
treatment
5-HT3 receptor antagonist before
each fraction, with or without
dexamethasone before the first five
fractions

23. 23
Previous Current
Low emetic risk
radiation therapy
5-HT3 receptor antagonist alone
as either prophylaxis or rescue.
For patients who experience
RINV while receiving rescue
therapy only, prophylactic
treatment should continue until
radiotherapy is complete
Adult patients treated with radiation
therapy to brain should be offered
rescue dexamethasone therapy.
Adult patients who are treated with
radiation therapy to the head and
neck, thorax, or pelvis should be
offered rescue therapy with a 5-HT3
receptor antagonist, dexamethasone,
or a dopamine receptor antagonist
minimal-emetic-risk
radiation therapy
rescue therapy with either a
dopamine receptor antagonist
or a 5-HT3 receptor antagonist.
Prophylactic antiemetics should
continue throughout radiation
treatment if a patient
experiences RINV while
receiving rescue therapy.
Rescue therapy with a 5-HT3 receptor
antagonist, dexamethasone, or a
dopamine receptor antagonist

24. 24
Previous Current
Concurrent
radiation and
antineoplastic
agent therapy
Patients should receive
antiemetic prophylaxis according
to the emetogenicity of
chemotherapy, unless the
emetic risk with the planned
radiotherapy is higher.
Adult patients treated with
concurrent radiation and
antineoplastic agents should receive
antiemetic therapy appropriate for
the emetic risk level of the
antineoplastic agents, unless the risk
level of the radiation therapy is
higher.
During periods when prophylactic
antiemetic therapy for the
antineoplastic agents has ended, and
ongoing radiation therapy would
normally be managed with its own
prophylactic therapy, patients should
receive prophylactic therapy
appropriate for the emetic risk of the
radiation therapy until the next
period of antineoplastic therapy,
rather than receiving rescue therapy
for the antineoplastic agents as
needed

25. 25
Pediatric Patients Previous Current
Optimal treatment
to prevent nausea
and vomiting from
high emetic risk
antineoplastic
agents in pediatric
patients
combination of a 5-HT3
antagonist plus a
corticosteroid is suggested
before chemotherapy in
children receiving
chemotherapy of high or
moderate emetic risk.
Because of variation of
pharmacokinetic parameters
in children, higher weight-
based doses of 5-HT3
antagonists than those used in
adults may be required for
antiemetic protection.
Pediatric patients treated with high
emetic-risk antineoplastic agents
should be offered a three-drug
combination of a 5-HT3 receptor
antagonist, dexamethasone, and
aprepitant
Pediatric patients treated with high
emetic-risk antineoplastic agents who
are unable to receive aprepitant
should be offered a two-drug
combination of a 5-HT3 receptor
antagonist and dexamethasone
Pediatric patients treated with high-
emetic-risk antineoplastic agents who
are unable to receive dexamethasone
should be offered a two-drug
combination of palonosetron and
aprepitant

26. 26
Pediatric Patients Previous Current
Optimal treatment to
prevent nausea and
vomiting from
moderate emetic risk
antineoplastic agents
in pediatric patients
combination of a 5-HT3
antagonist plus a
corticosteroid is suggested
before chemotherapy in
children receiving
chemotherapy of high or
moderate emetic risk.
Because of variation of
pharmacokinetic
parameters in children,
higher weight-based doses
of 5-HT3 antagonists than
those used in adults may be
required for antiemetic
protection.
Pediatric patients treated with
moderate-emetic-risk antineoplastic
agents should be offered a two-drug
combination of a 5-HT3 receptor
antagonist and dexamethasone
Pediatric patients treated with
moderate-emetic-risk antineoplastic
agents who are unable to receive
dexamethasone should be offered a
two-drug combination of a 5-HT3
receptor antagonist and aprepitant
Low emetic risk Not addressed Pediatric patients treated with low-
emetic-risk antineoplastic agents
should be offered ondansetron or
granisetron

27. 27
Previous Current
Minimal emetic risk Not addressed Pediatric patients treated with minimal
emetic risk antineoplastic agents
should not be offered routine
antiemetic prophylaxis

28. • Antiemetic Dosing for Adults by Chemotherapy Risk Category
28
Emetic Risk Category Dose on Day of Chemotherapy Dose on Subsequent Days
High: Cisplatin and
other agents
NK1 receptor antagonist
(plasma half life)
Aprepitant (9 - 14 hr)
Fosaprepitant (9 - 14 hr)
Netupitant (96 hr) -
palonosetron
Rolapitant (180 hr)
125 mg oral
150 mg IV
300mg netupitant/ 0.5mg
palonosetron oral in single capsule
(NEPA)
If netupitant-palonosetron is used, no
additional 5-HT3 receptor antagonist is
needed
180 mg oral
80 mg oral on days 2 and 3

29. • Antiemetic Dosing for Adults by Chemotherapy Risk Category
29
Emetic Risk Category Dose on Day of Chemotherapy
High: Cisplatin and other
agents
5-HT3 receptor antagonist
Granisetron (9 hr)
Ondansetron (4 hr)
Palonosetron (40 hr)
Dolasetron (7 hr)
Tropisetron (6 hr)
Ramosetron (6 hr)
2 mg oral or 1 mg or 0.01 mg/kg IV or 1 transdermal patch or 10
mg subcutaneous
8 mg oral twice daily or 8 mg oral dissolving tablet twice daily or
three 8 mg oral soluble films or 8 mg or 0.15 mg/kg IV
0.50 mg oral or 0.25 mg IV
100 mg oral only
5 mg oral or 5 mg IV
0.3 mg IV

30. 30
Emetic Risk Category Dose on Day of
Chemotherapy
Dose on Subsequent Days
High: Cisplatin and
other agents
Dexamethasone
• If aprepitant is used
• If fosaprepitant is
used
• If netupitant-
palonosetron is
used
• If rolapitant is used
• If no NK1 receptor
antagonist used
Olanzapine
12 mg oral or IV
12 mg oral or IV
12 mg oral or IV
20 mg oral or IV
20 mg oral or IV
10 mg oral
8 mg oral or IV once daily on days 2-4
8 mg oral or IV on day 2; 8 mg oral or IV
twice daily on days 3 and 4
8 mg oral or IV once daily on days 2-4
8 mg oral or IV twice daily on days 2-4
8 mg oral or IV twice daily on days 2-4
10 mg oral on days 2-4

31. • Antiemetic Dosing for Adults by Chemotherapy Risk Category
31
Emetic Risk Category Dose on Day of Chemotherapy Dose on Subsequent Days
High: Anthracycline
combined with
cyclophosphamide
NK1 receptor antagonist
5-HT3 receptor antagonist
Dexamethasone
• If aprepitant is used
• If fosaprepitant is used
• If netupitant-
palonosetron is used
• If rolapitant is used
Olanzapine
Same as before
Same as before
12 mg oral or IV
12 mg oral or IV
12 mg oral or IV
20 mg oral or IV
Same as before
Same as before
Same as before
Same as before

32. • Antiemetic Dosing for Adults by Chemotherapy Risk Category
32
Emetic Risk Category Dose on Day of Chemotherapy
Moderate or low risk
5-HT3 receptor antagonist
Granisetron
Ondansetron
Palonosetron
Dolasetron
Tropisetron
Ramosetron
2 mg oral or 1 mg or 0.01 mg/kg IV or 1 transdermal patch or 10
mg subcutaneous
8 mg oral twice daily or 8 mg oral dissolving tablet twice daily or
8 mg oral soluble film twice daily or 8mg or 0.15 mg/kg IV
0.50 mg oral or 0.25 mg IV
100 mg oral only
5 mg oral or 5 mg IV
0.3 mg IV

33. 33
Emetic Risk Category Dose on Day of
Chemotherapy
Dose on Subsequent Days
Moderate
(If carboplatin area under
the curve is ≥ 4 mg/mL per
minute, add an NK1
receptor antagonist to the
5-HT3 receptor antagonist
and dexamethasone)
Dexamethasone 8 mg oral or IV
(Dexamethasone
dosing is day 1 only: 20 mg
with rolapitant, and 12 mg
with aprepitant,
fosaprepitant, or netupitant-
palonosetron)
8 mg oral or IV on days 2 and 3
(for moderate-emetic-risk agents
with a known risk for delayed
nausea and vomiting)
Low Risk
Dexamethasone 8 mg oral or IV

34. Potential Side effects
• 5-HT3 antagonists: QTc prolongation (not palonosetron),
increased liver function tests, generally mild symptoms
(headache, constipation, diarrhea)
• NK-1 antagonists: weakness, dizziness, diarrhea, constipation,
flatus, abdominal discomfort, reflux symptoms, hiccups,
headache
• Cannabinoids: mood changes; disorientation; dizziness; brief
impairment of perception, coordination, and sensory
functions; tachycardia; hypotension
34

35. Guidelines for HEC
35
Acute CINV Delayed CINV (Day 2-4)
NCCN 5-HT3 RA + Dex + NK-1 RA
Or
NEPA + Dex
Or
Olanzapine + Palonosetron + Dex
Or
5-HT3 RA + Dex + Aprepitant + Olanzapine
Dex  Aprepitant
Or
Dex
Or
Olanzapine
Or
Olanzapine + Dex  Aprepitant
ASCO 5-HT3 RA + Dex + NK-1 RA + Olanzapine Olanzapine + Dex  Aprepitant
MASCC 5-HT3 RA + Dex + NK-1 RA + Olanzapine Olanzapine + Dex  Aprepitant

36. Guidelines for MEC
36
Acute CINV Delayed CINV (Day 2-3)
NCCN 5-HT3 RA (Palonosetron or granisetron s.c.
preferred) + Dex  NK-1 RA
Or
NEPA + Dex
Or
Olanzapine + Palonosetron + Dex
5-HT3 RA ( if palonosetron or
granisetron preferred s.c.) OR
Dex  Aprepitant
Or
Dex
Or
Olanzapine
ASCO 5-HT3 RA (palonosetron preferred) + Dex Dex
MASCC Palonosetron + Dex Dex

37. Guidelines for Low & Minimal Emetic Risk
37
Low risk Minimal Risk
NCCN 5-HT3 RA
Or
Dex
Or
Metoclopramide
Or
Prochlorperazine
No routine prophylaxis
ASCO Dex No routine prophylaxis
MASCC 5-HT3 RA
Or
Dex
Or
Doapmine RA
No routine prophylaxis

38. 38
Minimal Low Moderate High
Rescue Therapy Rescue Therapy 5-HT3 receptor
antagonist
with or without
dexamethasone
5-HT3 receptor
antagonist
and dexamethasone
Summary

39. 39
Thank You