Title: Evidence, Challenges
1Evidence, Challenges and Solutions Preventing
and Managing Chemotherapy-Induced Nausea and
Vomiting
Scott Edwards, Pharm D Clinical Oncology
Pharmacist Eastern Health, St. Johns, NL NOPS
2008
2Patient Perceptions of the Most Severe Side
Effects of Cancer Chemotherapy
Rank 19831 19932 19953 19994
1. Vomiting Nausea Nausea Nausea
2. Nausea Constantly tired Loss of hair Loss of hair
3. Loss of hair Loss of hair Vomiting Constantly tired
4. Thought of coming for treatment Effect on family Constantly tired Vomiting
5. Length of time treatment takes Vomiting Having to have an injection Changes in the way things taste
Adapted from 1Coates A et al. Eur J Cancer Clin
Oncol. 198319203-8. 2Griffin AM et al. Ann
Oncol. 19967189-95. 3De Boer-Dennert M et al.
Br J Cancer. 1997761055-61. 4 Lindley C et al.
Cancer Pract 1999759-65.
3CINV - Definitions
- Acute within a few minutes to several hours
after drug administration and commonly resolves
within 24 hours. - Delayed develops in patients more than 24 hours
after chemotherapy administration. - May last up to 6 days
- It commonly occurs with cisplatin, carboplatin,
cyclophosphamide and/or anthracyclines. - Anticipatory nausea and/or vomiting before
patients receive their chemotherapy, after a
prior negative experience with chemotherapy - Breakthrough occurs despite prophylactic
treatment and/or requires rescue. - Refractory nausea and emesis during subsequent
cycles when antiemetic prophylaxis and/or rescue
have failed in earlier cycles
- Adapted from
- ASHP Am J Health Syst Pharm 199956729-764
- NCCN Practice Guidelines in OncologyVersion 3.
2008. Antiemesis
4Rates of CINV
Adapted from 1. Hickok JT, et al. Cancer.
2003972880-6. 2.http//www.ashpadvantage.com/pre
vious_meetings/mcm_2005/cemornings2005/CEM_CINV_ha
ndout.pdf
5Chemotherapy-Induced Emesis Risk Factors
- Patient-related risk factors include
- Younger age
- Female gender
- No/minimal prior history of alcohol use
- Prior CINV
- Anxiety
- High pretreatment expectation of severe nausea
- Adapted from
- Gregory RE et al. Drugs. 1998. 2. Hesketh PJ et
al. J Clin Oncol. 1997. - Roscoe JA, Bushunnow P, Morrow GR, et al. Patient
experience is a strong predictor of severe nausea
after chemotherapy a University of Rochester
Community Clinical Oncology Program study of
patients with breast carcinoma. Cancer
20041012701-2708
6Influence of Patient Expectations on CINV
- Expectancy of nausea assessed before patients
received their first doxorubicin-based
chemotherapy treatment was found to be a strong
predictor of subsequent nausea.
Adapted from Roscoe et al. Cancer. 2004
101(11)2701-8.
7Chemotherapy-Induced Emesis Risk Factors
- Treatment-related risk factors include
- High drug dose
- High emetogenicity of chemotherapy drugs
- Of all the known predictive factors, the
emetogenicity of a given chemotherapeutic agent
is the predominant factor.
Adapted from ASHP Am J Health Syst Pharm
199956729-64.
8Causes of CINV
- In addition to emesis induced by chemotherapy,
CINV can be caused by - Partial or complete bowel obstruction
- Vestibular Dysfunction
- Brain Metastases
- Electrolyte imbalance hypercalcemia,
hyperglycemia, hyponatremia, uremia - Concomitant drugs, including opiates
- Gastroparesis induced by a tumor or chemotherapy
(such as vincristine) - Psychophysiologic factors, including anxiety as
well as anticipatory nausea and vomiting
Adapted from NCCN Practice Guidelines in
OncologyVersion 3. 2008. Antiemesis.
9Consequence of Unresolved CINV
Adverse sequelae of nausea and vomiting in the
cancer patient.
- Discontinuation of therapy
- Serious metabolic derangements
- Nutritional depletion and anorexia
- Esophageal tears
- Wound dehiscence
- Deterioration of patients physical and mental
status - Degeneration of self-care and functional ability
Adapted from NCCN Practice Guidelines in
OncologyVersion 3. 2008. Antiemesis.
10Poll of the audienceAs Health care professionals
we often
-
- A. Accurately recognize the incidence of acute
and delayed CINV in our own practices. - B. Underestimate the incidence of acute and
delayed CINV in our own practices.
11Anti Nausea Chemotherapy Registry (ANCHOR) study
- The authors determined the incidence of acute and
delayed CINV after modern antiemetics. - Then they compared the actual incidences of CINV
to the predictions made by physicians and nurses
regarding these patients.
Adapted from Grunberg SM et al. Cancer
20041002261-8.
12Anchor Study Perception vs Reality Moderately
Emetogenic Chemotherapy
Adapted from Grunberg et al. Cancer
20041002261-8.
13Toxicity Assessments
Dr. H. Bliss Murphy Cancer Center, St. Johns
Newfoundland
- Grade common toxicity effects of adjuvant breast
cancer patients. - Patients are assessed the day of chemotherapy and
again 2-3 days post chemotherapy. - Patients also have a number to call back if they
experience any toxicities.
14Rates of CINV in
Dr. H. Bliss Murphy Cancer Center, St. Johns
Newfoundland
N26
15Rate of CINV
at the Dr. H. Bliss Murphy Cancer Center, St.
Johns Newfoundland in comparison to the Grunberg
data
N231
Adapted from Cancer 20041002261-8.
16Health Care Professionals Perception of CINV at
the Dr. H. Bliss Murphy Cancer Center, St.
Johns Newfoundland
Adapted from Cancer 20041002261-8.
17 CINVDecreased Quality of Life
- CINV adversely impact patients' quality of life.
- Ovarian cancer patients in a recent study
included complete to almost complete control from
CINV among the most favorable health states, just
below perfect health and clinical remission.
Adapted from Support Care Cancer 200513219-27.
18 CINVDecreased Quality of Life
Adapted from Support Care Cancer 200513219-27.
19 CINVDecreased Quality of Life
- FLIE Questionnaire
- HEC-FLIE gt MEC-FLIE P0.0049
- FLIE-nausea gt FLIE-Vomiting P0.0097
- There is a greater negative impact onQOL from
nausea than there is from vomiting - There is a greater negative impact onQOL from
HEC than there is from MEC
FLIE Functional Living Index-Emesis HEC
highly emetogenic chemotherapy MEC moderately
emetogenic chemotherapy.
Adapted from Bloechl-Daum B et al. J Clin Oncol.
2006244472.
20Summary of the Importance of Prevention and
Treatment of CINV
- There still is a high level of anguish for CINV
experienced by our patients. - As health care professionals, we may not be
accurately predicting the level of CINV
experienced by our patients. - CINV has a enormous impact on our patients
quality of life.
21Mechanisms of 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.
Adapted from Berger AM et al. In Cancer
Principles and Practice of Oncology. 6th ed.
Lippincott Williams Wilkins 200128692880.
22Adapted from N Engl J Med 20083582482-94.
23Serotonin and 5-HT3 Receptor Pathway
- First recognized with high-dose metoclopramide.
- Development of 5-HT3 antagonists has had dramatic
impact - Highly effective in acute vomiting, less
effective for delayed events. - Optimal use is with dexamethasone.
- Primary mechanism of action appears to be
peripheral.
Adapted from Berger AM et al. In Cancer
Principles and Practice of Oncology. 6th ed.
Lippincott Williams Wilkins 20012869-80.
Gralla RJ et al J Clin Oncol 1999172971-94.
Antiemetic Subcommittee of the Multinational
Association of Supportive Care in Cancer. Ann
Oncol 19989811-19. Endo T et al Toxicology
2000153189-201. Hesketh PJ et al Eur J Cancer
2003391074-80.
24Substance P and Neurokinin1 (NK1) Receptor
Pathway
- High density of substance P/NK1 receptors located
in brain regions implicated in the emetic reflex. - Primary mechanism of NK1 receptor blockade action
appears to be central. - Effective for both acute and delayed events.
- Augments antiemetic activity of a 5-HT3 receptor
antagonist and corticosteroid.
Adapted from Hargreaves R J Clin Psychiatry
200263(suppl 11)18-24. Saria A Eur J Pharmacol
199937551-60. Hesketh PJ Support Care Cancer
20019350-54.
25Conceptual Model of Acute Delayed CINV
5-HT3-sensitive phase
Prokinetic-sensitive phase
NK1-sensitive phase
Intensity of emesis
Steroid-sensitive phase
Disrupted gut motility
5HT
Cell breakdown products
0
2
1
3
4
5
Time (days)
Adapted from Andrews Davis. In Andrews PLR
Sanger GJ (Eds). Emesis in Anti-Cancer Therapy
Mechanisms and Treatment. London Arnold
1993147.
26Pharmacogenomics
- Quest for individualized therapy.
- Identification and characterization of a large
number of genetic polymorphisms(biomarkers) in
drug metabolizing enzymes and drug transporters
may provide substantial knowledge about the
mechanisms of inter-individual differences in
drug response.
27Pharmacogenomics
- Pharmacogenomics - the study of the relationship
between specific DNA sequence variations and the
actual effect of a drug. - CYP2D6 is involved in the metabolism of all of
the most commonly available serotonin
antagonists, except granisetron, and their
efficacy and side effects may therefore be
affected by the CYP2D6 polymorphism. As this
enzyme is polymorphic, several different alleles
may be present in different individuals.
28Pharmacogenomics Polymorphic Distribution
- CYP2D6 mutations or deletions, poor metabolizer
(PM), occur in 10 of the general population - (UM) Ultrarapid metabolizer phenotype is observed
in 2 of the general population. - EM (extensive metabolizer), which is the normal
or usual phenotype.
Number of Subjects
PM
EM
URM
Increasing Metabolic Capacity
29Pharmacogenomics in CINV
- Kaiser studied the impact of patient genotype for
2D6 (CYP2D6) on efficacy of ondansetron and
tropisetron for CINV. - The ultrarapid metabolizer patients experienced
significantly more nausea and vomiting after
chemotherapy. - The impact of genotype on vomiting incidence was
observed during both early (hours 0 to 4) and
late (hours 5 to 24) observation periods,
although delayed nausea and vomiting was not
evaluated in this study.
Adapted from Kaiser R, Sezer O, Papies A, et al
Patient-tailored antiemetic treatment with
5-hydroxytryptamine type 3 receptor antagonists
according to cytochrome P-450 2D6 genotypes. J
Clin Oncol 20 2805-11, 2002.
30Pharmacogenomics in CINV
Figure 2. Mean number of episodes of vomiting
(/- standard deviation) experienced 5-24 hours
after chemotherapy as a function of the number of
active cytochrome P450 CYP2D6 enzyme genes in
patients receiving tropisetron, 5 mg once a day
(A), and ondansetron, 8 mg twice a day (B)
Adapted from Kaiser R, Sezer O, Papies A, et al
Patient-tailored antiemetic treatment with
5-hydroxytryptamine type 3 receptor antagonists
according to cytochrome P-450 2D6 genotypes. J
Clin Oncol 202805-11, 2002.
31ANTIEMETIC GUIDELINE CONSENSUS
- Official Process Subscribed to by 9
International Oncology Groups -
International MASCC
North America
- U.S. ASCO, NCCN
- Canada CCO
Europe ESMO, EONS
Africa SASMO
Australia COSA
Adapted from MASCC Antiemetic March 2008
Guideline Update.
32MASCC (PERUGIA) 2004 ANTIEMETIC GUIDELINES
ANTIEMETIC TREATMENT GUIDELINES - The Four
Emetic Risk Groups -
HIGH Risk in nearly all patients (gt 90)
MODERATE Risk in 30 to 90 of patients
LOW Risk in 10 to 30 of patients
MINIMAL Fewer than 10 at risk
Adapted from MASCC Antiemetic March 2008
Guideline Update.
33MASCC (PERUGIA) 2004 ANTIEMETIC GUIDELINES
- Emetic Risk Groups - Single IV Agents -
HIGH Cisplatin Mechlorethamine Streptozocin Cyclophosphamide gt 1500 mg/m2 Carmustine Dacarbazine Cisplatin Mechlorethamine Streptozocin Cyclophosphamide gt 1500 mg/m2 Carmustine Dacarbazine
MODERATE Oxaliplatin Cytarabine gt1 gm/m2 Carboplatin Ifosfamide Cyclophosphamide lt1500 mg/m2 Doxorubicin Daunorubicin Epirubicin Idarubicin Irinotecan
Adapted from MASCC Antiemetic March 2008
Guideline Update.
34MASCC (PERUGIA) 2004 ANTIEMETIC GUIDELINES
- Committee I (3/5) Emetic Risk Groups - Single
IV Agents
LOW Paclitaxel Docetaxel Mitoxantrone Topotecan Etoposide Pemetrexed MethotrexateDoxorubicin HCL liposome injection Mitomycin Gemcitabine Cytarabine lt100 mg/m2 5-Fluorouracil Bortezomib Cetuximab Trastuzumab
Adapted from MASCC Antiemetic March 2008
Guideline Update.
35MASCC (PERUGIA) 2004 ANTIEMETIC GUIDELINES
ANTIEMETIC TREATMENT GUIDELINES - Committee I
(5/5) Emetic Risk Groups - Single Oral Agents -
HIGH Hexamethylmelamine Procarbazine Hexamethylmelamine Procarbazine
MODERATE Cyclophosphamide Etoposide Temozolomide Vinorelbine Imatinib
LOW CapecitabineTegafur uracil CapecitabineTegafur uracil
MINIMAL Chlorambucil Hydroxyurea L-Phenylalanine mustard 6-Thioguanine Methotrexate Gefitinib
Adapted from MASCC Antiemetic March 2008
Guideline Update.
36Principles of Care for Acute Highly
andModerately Emetic Settings
- UNANIMOUS CONSENSUS CATEGORY 1 EVIDENCE
- Use the lowest tested fully effective dose.
- No schedule is better than a single dose given
before chemotherapy. - The antiemetic efficacy and adverse effects of
serotonin antagonist agents are comparable in
controlled trials. - Intravenous and oral formulations are equally
effective and safe. - Always give dexamethasone with a 5-HT3 antagonist
before chemotherapy.
Adapted from MASCC Antiemetic March 2008
Guideline Update.
37Guideline for the Prevention of Acute Nausea and
Vomiting Following Chemotherapy of High Emetic
Risk
- To prevent acute vomiting and nausea following
chemotherapy of high emetic risk, a three-drug
regimen is recommended including single doses of - 5-HT3 antagonist
- Dexamethasone
- Aprepitant (or fosaprepitant)
- given before chemotherapy is recommended.
- MASCC Level of confidence High
- MASCC Level of consensus High
- ASCO Level of evidence I
- ASCO Grade of recommendation A
Adapted from slide from MASCC Antiemetic March
2008 Guideline Update.
38Guideline for the Prevention of Acute Nausea and
Vomiting Following Chemotherapy of Moderate
Emetic Risk (MEC)
- Example - Women receiving a combination of
anthracycline cyclophosphamide represent a
situation with a particularly great risk of
vomiting and nausea. To prevent acute vomiting
and nausea in these women, a three-drug regimen
including single doses of - 5-HT3 antagonist
- Dexamethasone
- Aprepitant (or fosaprepitant)
- given before chemotherapy is recommended.
- MASCC Level of confidence Moderate
- MASCC Level of consensus High
- ASCO Level of evidence II
- ASCO Grade of recommendation A
Adapted from MASCC Antiemetic March 2008
Guideline Update.
39Guideline for the Prevention of Acute Nausea and
Vomiting Following Chemotherapy of Moderate
Emetic Risk (MEC)
- In patients who receive MEC, not including a
combination of anthracycline plus
cyclophosphamide - 5-HT3 receptor antagonist
- Dexamethasone
- is recommended for prophylaxis of acute nausea
and vomiting in the first course. - MASCC level of confidence High
- MASCC level of consensus High
- ASCO level of evidence I
- ASCO grade of recommendation A
Adapted from MASCC Antiemetic March 2008
Guideline Update.
40B.C. Cancer Agency Antiemetic regimens
Adapted from Guidelines for Prevention and
Treatment of Chemotherapy-Induced Nausea and
Vomiting in Adults. Retrieved July 21, 2008 from
http//www.bccancer.bc.ca/NR/rdonlyres/8E898B5D-3F
12-4623-8E32-5B3C429C58F7/28155/SCNAUSEA_1Mar08.pd
f
41ONS Putting Evidence into Practice
Adapted from ONS PEP Nausea Retrieved July 21,
2008 from http//www.ons.org/outcomes/volume1/naus
ea/pdf/nauseaPEPCard.pdf
42ONS Putting Evidence into Practice Contd
Adapted from ONS PEP Nausea Retrieved July 21,
2008 from http//www.ons.org/outcomes/volume1/naus
ea/pdf/nauseaPEPCard.pdf
43Cancer Care Ontario - Telephone Nursing Practice
- and Symptom Management Guidelines
Adapted from CCO Telephone Assessments. Retrieved
July 21, 2008 from http//www.cancercare.on.ca/doc
uments/NursingTelephonePracticeGuidelines.pdf
44Cancer Care Ontario - Telephone Nursing
Practiceand Symptom Management Guidelines
Adapted from CCO Telephone Assessments. Retrieved
July 21, 2008 from http//www.cancercare.on.ca/doc
uments/NursingTelephonePracticeGuidelines.pdf
45Common CINV Challenges
- Challenges in multiple-day chemotherapy regimens
- Breakthrough CINV
- Anticipatory CINV
- Delayed CINV
46Multiple-Day Chemotherapy Regimens
- Challenge Patients receiving multi-day
chemotherapy (chemotherapy administered over
several days per cycle) are at risk for both
acute and delayed nausea and vomiting. - It is difficult to recommend appropriate
antiemetics for each day since acute and delayed
may overlap after the initial day of
chemotherapy. - The period of risk for delayed nausea and
vomiting also depends on the emetogenic potential
of the last chemotherapy agent administered in
the regimen.
Adapted from NCCN Practice Guidelines in
OncologyVersion 3. 2008. Antiemesis,
47Multi-Day Chemotherapy Regimens (continued)
- A 5-HT3 receptor antagonist should be
administered prior to each days 1st dose of
moderately or highly-emetogenic chemotherapy. - Dexamethasone should be administered once daily
either orally or IV for every day of
chemotherapy and for 2-3 days post chemotherapy. - Aprepitant may be used for multi-day
chemotherapy. Aprepitant 125 mg on day 1, then
aprepitant 80 mg daily on days 2 and 3 along with
dexamethasone. Based on Phase II data, aprepitant
may be safely administered on days 4 and 5 after
chemotherapy.
Adapted from NCCN Practice Guidelines in
OncologyVersion 3. 2008. Antiemesis,
48Breakthrough CINV
- Breakthrough emesis refers to vomiting that
occurs despite prophylactic treatment and/or
requires rescue. - Refractory emesis refers to emesis that occurs
during subsequent treatment cycles when
antiemetic prophylaxis and/or rescue have failed
in earlier cycles. - Challenge - Breakthrough nausea and vomiting
represents a difficult situation as ongoing
refractory nausea is hard to reverse.
Adapted from NCCN Practice Guidelines in
OncologyVersion 3. 2008. Antiemesis,
49Breakthrough CINV (continued)
- Management Strategies -Give around the clock
administration versus prn. -
- Additional agents should be from a different drug
class than initial therapy. No one treatment is
better than the other. - Possibilities include dopamine antagonists,
metoclopramide, haloperidol, cannabinoids,
corticosteroids, or agents such as lorazepam - If patient has dyspepsia, consider antacid
therapy (H2 blocker or Proton Pump Inhibitor).
Adapted from NCCN Practice Guidelines in
OncologyVersion 3. 2008. Antiemesis,
50Breakthrough CINV Contd
Adapted from Guidelines for Prevention and
Treatment of Chemotherapy-Induced Nausea and
Vomiting in Adults. Retrieved July 21, 2008 from
http//www.bccancer.bc.ca/NR/rdonlyres/8E898B5D-3F
12-4623-8E32-5B3C429C58F7/28155/SCNAUSEA_1Mar08.pd
f
51Anticipatory CINV
- Anticipatory nausea and/or vomiting is the
occurrence of nausea and/or vomiting before
patients receive their chemotherapy treatment.
Because it is a conditioned response, it can only
occur after a negative past experience with
chemotherapy. - Challenge - Anticipatory nausea and/or vomiting
occurs in 18 to 57 of chemotherapy patients. - Younger patients may be more susceptible as they
generally receive more aggressive therapy and
have poorer emesis control than older patients.
- Adapted from 1. Roscoe JA, et al. J Pain Symptom
Manage 200020113. - 2. Morrow GR, et al. Support Care Cancer
19986244.
52Anticipatory CINV (continued)
- The most effective way to treat is to prevent
CINV by using optimal antiemetics during every
cycle of therapy. - Either
- Alprazolam PO 0.25 to 0.5 mg t.i.d. beginning on
the night before treatment OR - Lorazepam 0.5-2 mg PO on the night before and the
morning of treatment. - Behavioral therapy
- Systemic densensitization
Adapted from NCCN Practice Guidelines in
OncologyVersion 3. 2008. Antiemesis,
53Delayed CINV
- Challenge - Delayed emesis is 2.5 times more
prevalent than acute emesis. - For moderately emetogenic chemotherapy
- Delayed nausea exceeds acute nausea by 16.
- Delayed emesis exceeds acute emesis by 15.
- For highly emetogenic chemotherapy
- Delayed nausea exceeds acute nausea by 27.
- Delayed emesis exceeds acute emesis by 38.
Adapted from Grunberg et al. Cancer 20041002261.
54Prognostic Factors for Delayed CINV
- Strongest predictor of delayed nausea and
vomiting was the occurrence of acute nausea and
vomiting. - Patients aged 52 years or younger and women were
more likely to have delayed nausea than were
those older than 52 years and men. - A high expectation of nausea was a significant
predictor of more severe nausea.
Adapted from The Lancet Oncology October
2005Vol(6)Issue(10)765-72.
55Case 1
- Initial Presentation
- Mary T. is a 56-year-old female who was
completely asymptomatic when a routine mammogram
showed two lesions. She underwent diagnostic
testing and had a mastectomy and auxiliary lymph
node dissection. - Diagnosis T3 (more than 5 cm) N0(0/6 lymph
nodes) M0. poorly differentiated invasive ductal
carcinoma of right breast, ER/PR positive and
HER-2/neu negative.
56Initial Presentation
- PAST MEDICAL HISTORY Unremarkable.
- SOCIAL HISTORY School teacher, married, mother
of two grown children living away, non smoker,
occasional drink on the weekends. - MEDICATIONS Ranitidine 150 mg b.i.d.,
- Lorazepam 1 mg prn
- SYSTEM INQUIRY Unremarkable.
- Allergies NKA (drugs, food, environmental
allergens)
57First Cycle of Chemotherapy (FEC)
- The patient is prescribed FEC (Fluorouracil,
Epirubicin, Cyclophosphamide) for 3 cycles
followed by Taxotere for 3 cycles. - She was given Ondansetron 8 mg and Dexamethasone
8 mg prior to her first cycle of chemotherapy. - She was given a prescription for Ondansetron 8
mg and Dexamethasone 4 mg po b.i.d. x 2 days post
chemotherapy as well as Metoclopramide 10 mg po
q6hprn to be taken post chemotherapy.
58Nausea post Cycle 1
- When she returned for cycle two she informed the
pharmacist that she had vomited on day 2 and that
she had experienced nausea for days 2-5 post
chemotherapy. - She rates this nausea as a 8/10 for days 2-4 and
6/10 for day 5.
59Case 1 Question 1
- What anti-emetics would you recommend to be given
prior to chemotherapy for her second cycle of
FEC? - Metoclopramide 10 mg
- Ondansetron 8 mg, Dexamethasone 8 mg and
- Aprepitant 125 mg
- Ondansetron 8 mg and Dexamethasone 8 mg
60Answer Question 1 B Guideline for the
Prevention of Acute Nausea and Vomiting Following
Chemotherapy of Moderate Emetic Risk (MEC)
- Women receiving a combination of anthracycline
cyclophosphamide represent a situation with a
particularly great risk of vomiting and nausea.
To prevent acute vomiting and nausea in these
women, a three-drug regimen including single
doses of - 5-HT3 antagonist
- Dexamethasone
- Aprepitant (or fosaprepitant)
- given before chemotherapy is recommended.
Adapted from MASCC Antiemetic March 2008
Guideline Update.
61Case 1 Question 2
- What anti-emetics would be offered to this
patient as an anti-nausea take home prescription
for the FEC (cycle 2) regimen? - A. Dexamethasone 8 mg bid x 3 days and
Metoclopramide 10 mg q6hprn. - B. Metoclopramide 10 mg q6hprn.
- C. Aprepitant 80 mg on days 2 and 3, Ondansetron
8 mg and Dexamethasone 4 mg bid x 2 days and
Metoclopramide 10 mg q6hprn.
62Answer Question 2
Adapted from http//www.bccancer.bc.ca.
63Case 1 Question 3
- What other actions can the pharmacist take to
help M.T. control her CINV?
64Answer Question 3
- Explore patient adherence with anti-emetics.
- Assess effectiveness/ineffectiveness of
anti-emetic plan. - Follow up toxicity assessments (use CCO telephone
toxicity guidelines). - CINV education.
- Communication with her other health care
providers. - Patient nausea diary (CANO patient education for
CINV). - Promote patient involvement through patient
resources - Chemotherapy and You A Guide to Self-Help During
Cancer Treatment, http//www.nci.nih.gov/cancerinf
o/chemotherapy-and-you - http//www.cancernausea.com
65Case 1 Question 4
- The pharmacist asks the patient what medications
she is currently taking. - She informs the nurse she is taking Warfarin,
Metoprolol and ASA. -
- Should she be concerned about a drug interaction
with Warfarin and Aprepitant?
66Case 1 Question 5
- Which of the following may occur with the
addition of aprepitant to M.Ts regimen? - A. INR may decline
- B. INR may increase
- C. Warfarin levels may rise
67Answer Question 4 and 5Warfarin Aprepitant
Interaction
- Aprepitant is a CYP3A4 substrate, a 3A4 inhibitor
and inducer, and a 2C9 inducer. - INR may decline.
Adapted from Aprepitant Monograph. Retrieved July
22, 2008 from http//www.cancercare.on.ca/pdfdrugs
/aprepitant.pdf
68Importance of Medication Reconciliation
- Pilot Project of Medication Reconciliation in St.
Johns, Newfoundland Cancer Center - Summer project
- Pharmacy Students
- Obtaining an accurate medication history for
chemotherapy patients
69Total Number of Medications vs. Total Number of
Inaccuracies or Omissions
Cancer Care Program
70Identification of the number of patients with
inaccuracies or omissions as well as the number
of drug related problems identified
Cancer Care Program
71Identification of the number of patients with
inaccuracies or omissions as well as the number
of patients taking OTC/Herbals
Cancer Care Program
72Starting Docetaxel after FEC
- M.T. completed her three cycles of FEC as part of
the FEC-D regimen. Since the addition of
Aprepitant, her nausea control has been much
better. - Since she is starting Docetaxel, she needs to
take Dexamethasone 8 mg po b.i.d. for 3 days,
starting 24 hours prior to chemotherapy. - The medical oncology team would like to keep M.T.
on Aprepitant due to her improved response.
73Case 1 Question 6
- As the oncology pharmacist, you tell the team
that they need to be concerned about Aprepitant
drug interactions. - Which of the following would be correct to tell
the team about Aprepitant - A. Aprepitant is a Substrate for CYP3A4,and
Moderate Inhibitor of CYP3A4. - B. Aprepitant is a Weak Inducer of CYP3A4 and
CYP2C9. - C. Both A and B are correct.
74Answer Question 6 - Aprepitant and P450
- Substrate for CYP3A4, CYP2C19 and CYP1A2
- Weak Inducer of CYP3A4 and CYP2C9
- Moderate Inhibitor of CYP3A4
- Weak inhibitor of CYP2C9 and CYP2C19
75Case 1 Question 7
- The general recommendations for dosing
dexamethasone when combined with Aprepitant is - A. Reduce the dose of dexamethasone by 50
- B. Increase the dose of dexamethasone by 50
- C. Do not adjust the dose of dexamethasone
76Answer Question 7
- Aprepitant increases the AUC of dexamethasone
when the two are administered concomitantly. - Reduce dexamethasone dose by 50.
77Case 1 Question 8
- What would be your recommendations for dosing
dexamethasone for Docetaxel premedication when
combined with Aprepitant for M.T. - A. Reduce the dose of dexamethasone by 50
- B. Increase the dose of dexamethasone by 50
- C. Do not adjust the dose of dexamethasone
78Case 2
- Jimmy T. is a A 27 year old with a history of
T2N2M1a, Stage III non-seminoma testicular
cancer. He had surgery for this and in follow up
was found to have metastatic disease. He had at
least two lung lesions as well as some
mediastinal adenopathy and retroperitoneal
adenopathy.
79Initial Presentation
- PAST MEDICAL HISTORY Unremarkable.
- SOCIAL HISTORY He lives with his common law
girlfriend, - Occasional drink on weekends, non smoker
- MEDICATIONS Acetaminophen prn
- SYSTEM INQUIRY Unremarkable.
- Allergies NKA (drugs, food, environmental
allergens)a
80First cycle of chemotherapy (BEP)
- The patient is prescribed BEP (BLEOMYCIN-ETOPOSIDE
-CISPLATIN) Chemotherapy for 4 cycles.
81Case 2 Question 1
- What anti-emetics would you recommend to be given
prior to chemotherapy for his first cycle of BEP? - Metoclopramide 10 mg pre chemotherapy for 5 days
- Ondansetron 8 mg, Dexamethasone 8 mg and
Aprepitant 125 mg on day 1 pre chemotherapy and
Ondansetron 8 mg, Dexamethasone 4 mg and
Aprepitant 80 mg on days 2-5 pre chemotherapy - Ondansetron 8 mg and Dexamethasone 8 mg pre
chemotherapy on days 1-5
82Answer Question 1Multiple Day Chemotherapy
- A 5-HT3 receptor antagonist should be
administered prior to each days 1st dose of
moderately or highly-emetogenic chemotherapy. - Dexamethasone should be administered once daily
either orally or iv for every day of
chemotherapy and for 2-3 days post chemotherapy. - Aprepitant may be used for multi-day
chemotherapy. Aprepitant 125 mg on day 1, then
aprepitant 80 mg daily on days 2 and 3 along with
dexamethasone. Based on Phase II data, aprepitant
may be safely administered on days 4 and 5 after
chemotherapy.
Adapted from NCCN Practice Guidelines in
OncologyVersion 3. 2008. Antiemesis,
83Case 2 Question 2
- The oncology pharmacist performs a toxicity
assessment on Jimmy T. 3 days (Monday afternoon)
post chemotherapy. The patient complains of
significant nausea that started on Sunday
evening. He vomited x 1 on Monday morning. He
rates the nausea as 8 out of 10. - He states he was given a prescription for
Ondansetron 8 and Dexamethasone 4 mg po bid x 2
days as well as Metoclopramide 10 mg po q6hprn.
The Dexamethasone and Ondansetron were completed
on Sunday morning. He did not take the
Metoclopramide as he wasnt sure if he should. - What should the oncology pharmacist do for this
patient?
84Answer Question 2 - Breakthrough CINV
- Management Strategies -Give around the clock
administration versus prn . - Additional agents should be from a different drug
class than initial therapy. No one treatment is
better than the other. - Possibilities include metoclopramide,
haloperidol, prochlorperazine, cannabinoids,
corticosteroids, or agents such as lorazepam. - If patient has dyspepsia, consider antacid
therapy - (H2 blocker or Proton Pump Inhibitor).
Adapted from NCCN Practice Guidelines in
OncologyVersion 3. 2008. Antiemesis,
85Case 2 Question 3
- Which of the following consequence of unresolved
CINV do you consider the most important for this
patient? - Nutritional depletion and anorexia
- Discontinuation of therapy
- Esophageal tears
86Unresolved issues in CINV?
- Role of risk factor assessment in tailoring
antiemetics to the individual at the onset of
chemotherapy. - Need to develop a better understanding of the
pathophysiology of delayed CINV. - Increase awareness of CINV for oncology
professionals. - Newer agents/ formulations
- Olanzapine
- New NK-1 antagonists
- New formulations of 5HT3 antagonists eg
transdermal - patches, oral sprays, longer acting SC
injections
87Emend Coverage
88Conclusion
- Chemotherapy-induced nausea/vomiting (CINV) is a
common side effect despite antiemetic therapy. - Health care professionals need to ensure patients
are being treated according to current antiemetic
guidelines. - It is always better and easier to PREVENT than
to treat nausea/vomiting associated with
chemotherapy.
89Acknowledgements
- Katrina Mulherin, Pharm D Student
- Barbara Wilson, RN, BN, MS, CON(C)
- Staff (nurses, physicians, pharmacists) at St.
Johns Cancer Center