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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
Chemotherapy-Induced Nausea and Vomiting
Anne M. Hendricks
Ferris State University
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
Abstract
Inconsistent usage of antiemetic therapies during chemotherapy treatment led me to research the
latest evidence, develop charts for staff, and tracking mechanisms for inconsistencies. I utilized
information from our Oncology Pharmacist (Joanne McGurn) and several evidence-based
research articles to formulate charts of the recommended treatments and dosages for high,
moderate and low emetogenic chemotherapy (Appendixes A,B,C). I placed the charts in our
medication room in a binder, and sent copies to all seven Oncologists that we serve. I developed
a chart that measures each time a correction is required for specific physicians (Appendix D). I
developed another chart to measure patient subjective perceptions of nausea and vomiting
(Appendix E). Severity of nausea symptoms was measured by number 1-4, with 1=minor
nausea/vomiting, 2=more severe nausea/vomiting which influences activity slightly, 3= very
activity limiting nausea/vomiting, 4=debilitating nausea/vomiting. Continued research of
monthly data and collaboration with physician/pharmacist will ensure best patient outcome
through continuity of care.
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
Chemotherapy-Induced Nausea and Vomiting
I work in the Infusion Clinic at Munson Medical Center and I have a National Oncology
Certification. I have noticed some inconsistency with the usage of antiemetics amongst
physicians treating our cancer patients. Our Oncologists tend to rely on nursing or pharmacy to
catch/correct antiemetic errors. Because of the dynamic nature of cancer and chemotherapy
treatments, and the different Oncologists’ preferences for antiemetics, it is difficult for the nurse
to know if the antiemetic chosen is appropriate. There are times when the most appropriate
medication is missed and the patient suffers. I wanted to develop a way to promote patient
comfort by ensuring proper, consistent antiemetic usage and prevent chemotherapy-induced
nausea and vomiting. My research is from the most current antiemetic studies which I have
summarized.
My first research was a study performed by Warr and Oliver (2005) regarding
Neurokinin-1 (NK1) receptor antagonist (Aprepitant). Warr and Oliver’s (2005) study came from
randomized controlled trials, one systematic review, and one meta-analysis; and the funding
came from Cancer Care Ontario and Ontario Ministry of Health and Long-Term Care. The
subjects were > 16 years old, with a Karnofsky performance Index > 60, which meant that they
were at least able to perform normal activities without much assist and able to live at home
(Warr & Oliver, 2005). The subjects were stratified by gender, had solid tumors, and were to be
receiving high dose Cisplatin, chemotherapy with a high emetogenic index (Warr &
Olviver,2005). Differing doses of Aprepitant from 40 mg- 400 mg were compared, with 125 mg
being the most efficacious by showing 90% receptor occupancy on day one of treatment (Warr &
Oliver,2005). The five trials revealed a significant increase, 12.5 %-20 %, in complete protection
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
from nausea and vomiting with Aprepitant (Warr & Oliver, 2005).
Another study by Kris et al.(2006) published in the American Society of Clinical
Oncology analyzed antiemetic data found in the Medline Database and Cochrane Library.
Update committee members contributed articles and reviewed collected material on published,
randomized, controlled trials in phase II and III (Kris et al.,2006). The focus was on Aprepitant,
(Neurokinin-1 [NK1] receptor antagonists), 5-hydroxytryptamine(3) (5-HT3) receptor
antagonists and Dexamethasone in high-dose Cisplatin therapy (Kris et al.,2006). The study
defined chemotherapy emetic risks as High: 90% chance, Moderate: 30%-90%, Low: 10%-30%,
and Minimal: <10% (Kris et al.,2006). The study also gave recommendations for antiemetic
regimens based on the chemotherapy emetic potential. High: 5-HT3, Dexamethasone and
Aprepitant pre-chemo day 1, Aprepitant and Dexamethasone day 2 and day 3 (Kris et al.,2006).
Moderate: 5-HT3, Dexamethasone and Aprepitant day 1 and 5-HT3 or Dexamethasone day 2
and day 3 and Low: Dexamethasone pre, no delayed prevention routinely (Kris et al.,2006). Kris
et al.(2006) also noted that combination chemotherapy regimens require treating the highest
emetic risk and multiple-consecutive days of chemotherapy require treating the highest emetic
risk each day of therapy and 2 days post treatment.
The study by Kris et al.,(2006) did offer
one area of concern regarding the NK1 decreasing clearance of certain chemotherapies via
cytochrome P450 (CYP3A4), leading to potential toxicity, but stressed that there is not enough
evidence to support this at this time.
The third source of information is from the National Comprehensive Cancer Network
(NCCN) guidelines (2008) found at http://www.nccn.org, which, according to J. McGurn, PhD,
are the guidelines followed by our Oncology pharmacy (personal communication, October
29,2008). The NCCN uses a multidisciplinary panel to review the latest treatments, support
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
clinical trials, and update its guidelines with the most current and comprehensive information
available (NCCN, October 2008). For the purpose of this paper, I mention only the latest
findings from the website which are in addition to my research defined above. More information
is available at the website (http://www.nccn.org). According to the NCCN (2008) guidelines a
new FDA approved drug for high and moderate emetogenic chemotherapy was introduced:
Fosaprepitant Dimeglumine 115 mg intravenous administered over 15 minutes can replace
Aprepitant 125 mg orally on day 1 of treatment, followed by Aprepitant oral 80 mg day 2 and
day 3. Careful monitoring of drugs metabolized by cytochrome P450 and enzyme 3A4
(CYP3A4) is suggested when using the drug Aprepitant because it can alter metabolism
(NCCN,2008,MS-4). The NCCN (2008) mention another drug Palnosetron, 5-HT3 antagonist
with 100-fold higher binding affinity compared to other 5-HT3, which has a half-life of
approximately 40 hours and has shown superiority in delayed emesis. The NCCN does state that
further research is being performed on safety of this drug, and I know that neither Palnosetron
nor Fosaprepitant Dimeglumine are in our hospital formulary as of yet (personal communication
J.McGurn, October 30,2008). The rest of the antiemetic protocols are as my prior research
showed.
How I conducted my research: I began in Medline Database under “antiemetics” and I
found several articles but I narrowed my search by choosing the most recent. I then called our
Oncology Pharmacist (J. McGurn) to find out what the current guidelines were for the hospital.
J.McGurn said that the pharmacists utilize http://www.nccn.org website then go under “Clinical
Practice Guidelines in Oncology”, then under “Guidelines for Supportive Care”, then under
“Antiemesis”, and finally “V.3.2008”. I compiled a list of the drugs currently on formulary, both
chemo and antiemetic, to comprise charts (Appendix A,B,C) which I placed in the medication
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
room in an “important information” folder. The charts define which of the drugs that we use in
the clinic as High, Moderate or Low risk and have the appropriate antiemetic therapy available
below each category. I am hoping that this will be an easy reference tool to prevent antiemetic
errors. If a nurse finds a discrepancy she (all females in our clinic) is to alert the Oncology
Pharmacist who can then make a corrected order or refer the nurse to the appropriate Oncologist.
I am also going to send copies of the Appendix A-C to each of the Oncologists.
I hope to measure our success by keeping a check sheet with dates for each calendar
month and each of our Oncologists’ names, so that if a nurse finds an error in antiemetic that
requires correction by physician or pharmacist they mark the appropriate physician
corresponding with appropriate date of occurrence (Appendix D). Comparison studies for each
calendar month will be kept for reference.
Another measure (Appendix E) will be subjective information gathered from the patient.
The nurses are to record nausea and vomiting with a patient-defined number of severity: 1=mild
nausea, 2=Slight nausea/vomiting: interferes somewhat with activity, 3=Severe nausea/vomiting:
interferes greatly with activity, 4=Debilitating nausea/vomiting: unable to care for self. Patient
name sticker will be placed, which also has physician name, in the date correlating with
symptoms. This chart can be used in many ways, to monitor the physician, the patient, and the
chemotherapy for any patterns. The information can be utilized by the nurses, physicians and
pharmacists.
The nursing theory that I felt most related to my project was Kolcaba’s Theory of
Comfort which, according to Alligood and Tomey (2006), states that health care needs are needs
of comfort which can be measured by nursing interventions specific to the patient. According to
Herrstedt (2007) patients consider nausea and vomiting some of the worst side-effects of chemo.
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
Navari (2003) sites chemo-induced nausea and vomiting as a condition to “quality of life”. I feel
that if nausea and vomiting can be controlled through consistent use of antiemetics then patients’
healthcare needs of comfort will be better met.
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
References
Alligood,M.R.,&Tomey,A.M.(2006).Nursing Theorists and Their Work (6th ed.). Missouri:
Mosby-Elsevier.
Food and Drug Administration. (2008,October). RX Trials institute drug pipeline alert: AP
Pharma gets mixed results. 6 (41). Retrieved October 23, 2008, from
http://fdanews.com/newsletter/article?issueId=12025&articleId=111062
Herrstedt,J.(2007). Medical treatment of chemotherapy-induced nausea and vomiting. Ugeskr
Laeger,169(9),799-805.
Kris, M.G.,Hesketh,P.J.,Somerfield,M.R.,Fever,P.,Clark- Snow,R.,Koeller,J.M.,et al. (update
2006). Guideline for antiemetics in oncology. American Society of Clinical
Oncology,24(18)1-16.[110references].
National Comprehensive Cancer Network. (2008,February 5). Clinical practice guidelines in
oncology: Guidelines for supportive care-Antiemesis. (v.3 2008)[electronic version]
retrieved October 30,2008, from
http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf.
Navari,R.M.(2003).Pathogenesis-based treatment of chemotherapy-induced nausea and
vomiting—two new agents. Journal of Supportive Oncology, 1(2),89-103.
Warr,D.& Oliver,T. (2005). The role of neurokinin-1 receptor antagonists in the prevention of
emesis due to high-dose cisplatin. Cancer Care Ontario (2005, April 5).p.27 (Evidencebased series no.12-4).[20 references].
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
Appendix A
Antiemetic Chart
High Emetogenic: (90 % likelihood of emesis)
Adriamycin and Cytoxan
Cisplatin
Cytoxan >1500mg/m2
DTIC
Antiemetic regimen:
Aprepitant 125 mg PO day 1, 80mg PO day 2 and day3
OR
Fosaprepitant dimeglumine 115mg IV day 1,
aprepitant 80mg PO day 2 and day3
AND
Dexamethasone 12 mg PO/IV day1, 8 mg PO/IV days 2-4
AND
5-HT3 antagonist
Ondansetron 16-24 mg PO or 8-12 mg (max. 32 mg) IV day 1
OR
Granisetron 2 mg PO or 1 mg PO BID or max 1mg IV day 1 OR
Palososetron 0.25 mg IV day 1 AND
prn. Lorazepam 0.5-2 mg PO/IV/SL every 4-6 hours days 1-4
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
Appendix B
Antiemetic Chart
Moderate emetogenic: (30-90% frequency of emesis)
Amifostine >300mg/m2
Carboplatin
Cisplatin <50 mg/m2
Cytoxan < 1500mg/m2 or PO
Doxorubicin, Daunorubicin, Epirubicin, Idarubicin
Etoposide
Ifosfamide
Irinotecan
Methotrexate
Oxaliplatin >75mg/m2
Antiemetic regimen: Aprepitant 125 mg PO day 1, 80 mg PO day 2 and day 3 OR
Fosaprepitant dimeglumine 115 mg IV day 1 with Aprepitant 80 mg PO day 2 and day 3
Dexamethasone 12 mg PO/IV day 1, 8 mg PO/IV daily Or 4mg BID day 2-4
5-HT3 antagonist: Palonosetron 0.25 mg IV day 1
PO or 1 mg PO BID day 1
Or Granisetron 1-2mg
Or Ondansetron 16-24 mg PO or
max 32 mg/day IV
5-HT3 can be added day 2 and day 3. Lorazepam 0.5 mg-2 mg PO/IV/SL every 4-6 hours
as needed
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
Appendix C
Antiemetic Chart
Low Emetogenic: (10-30% frquency of emesis)
Amifostine < 300mg
Capecitabine
Cytarabine 100-2--mg/m2
Docetaxal
Doxorubicin (liposomal)
Etoposide
5-Flourouracil
Gemcitabine
Methotrexate 50-250mg/m2
Mitomycin
Mitoxantrone
Paclitaxel and Paclitaxel-albumin
Pemetrexed
Topotecan
Antiemetic regimen:
Dexamethasone 12 mg PO/IV daily OR
Prochlorperazine 10 mg PO/IV every 4-6hours OR
Diphenhydramine 25-50mg PO/IV every 4-6 hours OR
Lorazepam 0.5-2mg PO/IV every 4-6 hours if needed
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
Appendix D
Physician:
Dr. Gordon
Dr. Hughes
Dr. Kohler
Dr. Kosinski
Dr. Michelin
Dr. Ramsdell
Dr. Schwert
Dates the antiemetic order had to be corrected
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
Appendix E
Mon
Tue
Wed
Thu
November 2008
Fri
Place patient identification
On the correct date with number
3
4
5
6
7
corresponding to
Severity of nausea and vomiting:
1=Mild Nausea
10
11
12
13
14
2=Slight Influence on Activity
3=Very Activity Limiting Nausea and
Vomiting
17
18
19
20
21
24
25
26
27
28
4=Debilitating Nausea and Vomiting
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
Addendum
In the process of doing my research I remembered that one of our patients had
neurotoxicity thought related to chemotherapy, but was rather unusual. The patient didn’t have a
problem in the first treatment cycle, but developed a problem at the end of the second treatment
cycle. The patient became noticeably slower to process. The third cycle of treatment the patient
had definite processing deficits and had a facial twitch. The patient was stopped from receiving
the chemotherapy. This is a 44 year old man with a four year old daughter. I couldn’t stop
thinking about the patient, and wondering what was the difference between the first and the
subsequent rounds? I found an article describing a possible link between the antiemetic and
chemotherapy which may cause neurotoxicity (Howell, Szabatura, Jatfield, and Nesbit, 2008). I
remembered that in the first cycle of chemotherapy the patient was not on Aprepitant because it
was not prescribed, but, because he had severe nausea and vomiting, he was placed on
Aprepitant for the subsequent treatments. That was the answer to the difference between cycles
question. I then remembered that Aprepitant is the NK1 that can interfere with metabolism of
some medications (NCCN,2008). I further searched and found an article stating that the
chemotherapy the patient was receiving (Ifofsamide) may be one of the drugs that Aprepitant
interferes with (Howell,et al.,2008). Ifofsamide is “ metabolized by the cytochrome P450 system
to its active form, …a potential side effect is neurotoxicity, often manifesting as confusion,
hallucination, or seizure.” (Howell,et al., 2008).I shared the information with Joanne McGurn,
Oncology pharmacist, who has since shared the information with the physician and the U of M
Sarcoma Clinic, who are also involved in care. Last week the patient was able to receive an off
formulary drug, Palonosetron, that was the newest 5-HT3 agonists mentioned by NCCN 2008.
The patient has done well so far, and will continue treatment. I strongly believe that this is
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
evidence-based practice at its finest. My questioning and researching the latest evidence led to
an application in my own practice. This did change how the patient was treated in the future and
was shared with UofM as well, policies regarding this regimen were changed in our hospital to
avoid future problems.
The Oncologist called me personally to thank me and said, “Good catch”. I really wanted
to share this with you, I feel like this process has really helped me grow considerably in my
profession and, best of all, has possibly helped a patient.
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Running head: CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
References
Howell,J.E.,Szabatura,A.H.,Hatfield,S.A., & Nesbit,S.A.(2008).
Characterization of the occurrence of ifosfamide-induced neurotoxicity with concomitant
aprepitant. Journal of Oncology Pharmacy Practice,14(3),157-162.
National Comprehensive Cancer Network. (2008,February 5). Clinical practice guidelines in
oncology: Guidelines for supportive care-Antiemesis. (v.3 2008)[electronic version]
retrieved October 30,2008, from
http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf.