Journal of
Oncology Pharmacy Practice
Original Article
Compliance with National Comprehensive Cancer Network anti-emesis guidelines in a Community Hospital Cancer Center
J Oncol Pharm Practice 0(0) 1–5 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1078155214546563 opp.sagepub.com
Divya Daniel1 and Aubrey Waddell2,3
Abstract Objective: Nausea and vomiting are common adverse events exhibited by patients receiving chemotherapy. Prophylactic use of anti-emetic agents has been shown to reduce chemotherapy-induced nausea and vomiting. Compliance with the National Comprehensive Cancer Network anti-emesis guidelines (Version 1.2013) by practitioners in a community out-patient hospital (Blount Memorial Hospital) has been reviewed and the results are presented herein. Design: Retrospective study of patients receiving their first cycle of chemotherapy. Patients: A total of 487 patients were reviewed from January 2005 to July 2012. In total, 70 patients were categorized in the high-risk category, 292 patients were categorized in the moderate-risk category, 60 patients were categorized in the low-risk category, and 65 patients were categorized in the minimal-risk category as per the National Comprehensive Cancer Network guidelines. Included patients were being administered the first cycle of their first treatment at Blount Memorial Hospital. Data: Data were collected retrospectively from patient chemotherapy dispensing folders. Results: In all, 63% of the patients received appropriate anti-emetic prophylaxis medications as per the National Comprehensive Cancer Network guidelines. Post-comparison between outcomes based on the risk category showed that patients in the moderate-risk category were most likely (91%) and patients in the low-risk category were least likely (6.67%) to receive appropriate anti-emetic prophylaxis as per the National Comprehensive Cancer Network guidelines. Conclusion: Overall compliance with guidelines is acceptable. Patients in the moderate risk category are most likely to receive appropriate anti-emetic prophylaxis.
Keywords National Comprehensive Cancer Network, compliance, community hospital, anti-emesis
Introduction Chemotherapy-induced nausea and vomiting (CINV) is the one of the most common and historically feared side effects of chemotherapy.1 Prior to research leading to protocols detailing the proper use of anti-emetic agents for prophylaxis of CINV and the introduction of modern anti-emetics like 5-HT3 receptor antagonist (5HT3-RA), many patients avoided or delayed certain chemotherapy due to CINV.2 In addition to decreasing compliance with chemotherapy, CINV can also lead to other complications such as metabolic imbalances, anorexia, poor nutritional support.1,3 The combined morbidity caused by CINV has caused patients to
withdraw from potentially useful or curative chemotherapy. Appropriate use of anti-emetic agents has been shown to reduce or eliminate CINV in
1
2, University of Tennessee Health Science Center, College of Pharmacy, Knoxville, TN, USA 2 2, University of Tennessee Health Science Center, College of Pharmacy, Maryville TN, USA 3 2, Blount Memorial Hospital, Maryville TN, USA Corresponding author: Divya Daniel, University of Tennessee Health Science Center, College of Pharmacy, C/O 2014, 317 Mayhurst Lane, Cordova, TN 38018, USA. Email: [email protected]
Downloaded from opp.sagepub.com by guest on November 16, 2015
2
Journal of Oncology Pharmacy Practice 0(0)
approximately 70–80% of patients.4 Controlling adverse events in patients may positively impact patient compliance and, thus, decrease oncology patient morbidity.5 Guidelines serve as useful tools for practitioners to appropriately implement and integrate the latest clinical research into their practice.1 The National Comprehensive Cancer Network (NCCN) provides guidelines for practitioners to improve the quality and effectiveness of cancer care in oncology patients.6 The NCCN anti-emesis guidelines provide an overview of treatment to prevent CINV in patients receiving chemotherapy and are often used by practitioners in community oncology hospitals to set the standard of practice.2 Both the likelihood and severity of CINV vary dependent upon the chemotherapy agent used.7 The emetogenic potential of chemotherapy agents is classified into four different subtypes by the NCCN: high emetic risk, moderate emetic risk, low emetic risk, and minimal emetic risk. High emetic risk induces emesis in greater than 90% of treated patients, moderate emetic risk induces emesis in 30–90% of treated patients, low emetic risk induces emesis in 10–30% of treated patients, and minimal emetic risk induces emesis in less than 10% of treated patients.8 All the agents in the high emetic risk group and some agents from the moderate emetic risk group have the propensity to cause both acute and delayed CINV.6 While the type of chemotherapy agent is the primary risk factor for CINV, patient-specific risk factors also play affect the incidence of CINV in patients.1,2 Patient-specific risk factors include female gender, young age, history of alcohol intake, experience with emesis during pregnancy, impaired quality of life, and previous experience with chemotherapy.2 The NCCN does not specifically include patient-specific risk factors into the anti-emesis guidelines, but instead advise practitioners to chose anti-emetic regimens based both on the highest emetic risk and patient-specific risk factors.1,2 CINV is also classified as acute, delayed, anticipatory, breakthrough, and refractory. Anti-emetic prophylaxis is especially useful in acute, delayed, and some breakthrough CINV. Commonly used regimens include 5-hydroxytryptamine 3 receptor antagonists (5HT3-RAs) and a steroid. If delayed emesis is anticipated, a neurokinin 1 receptor antagonist (NK1-RA) is used as well. 5HT3-RAs have been shown to be among the most effective anti-emetic agents in acute CINV.7 Their development in the early 1990s has allowed for significant advancements in CINV treatment.9 All the 5HT3-RAs have been shown to be effective treatments for CINV and appear to be interchangeable.10 The lowest effective dose of each 5HT3-RA should be utilized. Common adverse events associated with 5HT3RAs include headache, lightheadedness, and sedation.11
Electrocardiography (ECG) changes, including QT prolongation, are among the more serious adverse events that can be associated with 5HT3-RAs. Palonosetron also appears to be effective in delayed CINV.12 The most recent NCCN anti-emesis Version 1.2014 recommends using palonosetron as the preferred 5HT3-RA for high- and moderate-risk anti-emesis. However, the objective of this research includes data derived from a range of 5HT3-RAs and is based on NCCN anti-emesis Version 1.2013. Steroids effectively control CINV—more-so when combined with a 5HT3-RA.1,2 Dexamethasone is used in prophylaxis regimens for high, moderate, and low emetic risk chemotherapy patients exhibiting CINV. This is combined with NK1RA for patients exhibiting delayed CINV. Common adverse events associated with dexamethasone include hyperglycemia, water retention, insomnia, and gastric discomfort.13 NK1-RA, aprepitant, prevents CINV, centrally in the brain stem and peripherally in the gastrointestinal tract, and is very effective in preventing delayed CINV.14 Adverse events associated with aprepitant include headache and fatigue. The NCCN guidelines Version 1.2013 recommends the use of a 5HT3-RA + steroid + NK1-RA for prophylaxis of high-risk anti-emesis, a 5HT3-RA + steroid (NK1RA) for prophylaxis of moderate-risk anti-emesis, steroid/piperazine anti-emetic/dopamine antagonist/ benzodiazepine for prophylaxis of low-risk anti-emesis, and no prophylactic emesis is recommended for minimal-risk anti-emetic. The primary goal of this project was to retrospectively measure oncologists’ compliance with the NCCN anti-emesis guidelines Version 1.2013 at the onset of a patient’s first chemotherapy cycle. Secondary objectives were to determine how many patients received higher/ lower than needed anti-emetic doses and their distribution within emesis risk categories.
Methods Study population Oncology patients from January 2005 to July 2012 were used in this study. Data were collected from patient chemotherapy dispensing folders and all patient-specific information was discarded—no patients and/or families were contacted. The study was approved by the Investigational Review boards of Blount Memorial Hospital and University of Tennessee Health Science Center, Knoxville Campus. Data were recorded during the first cycle of chemotherapy treatment. Included were chemotherapy agents used, whether or not an anti-emetic was prescribed prophylactically, and if so what anti-emetic agent was used.
Downloaded from opp.sagepub.com by guest on November 16, 2015
Daniel and Waddell
3
The NCCN guidelines were used to classify chemotherapy agents under high emetic risk, moderate emetic risk, low emetic risk, or minimal emetic risk category. We did not include patient-specific risk factors while classifying risk status. Patients received all prophylactic anti-emetic medications in the hospital if they were in-patients, or in the out-patient clinic if they were out-patients. When evaluating multiple day chemotherapy regimens, compliance was based on prophylaxis on day 1, since patients were evaluated on a daily basis. For the determination of inappropriate dosage, dexamethasone doses greater than 12 mg or the administration of non-NCCN recommended drug for anti-emesis prophylaxis was considered inappropriate. The inclusion criteria of this study were patients diagnosed with cancer and received at least their first cycle of chemotherapy between January 2005 and July 2012 at Blount Memorial Hospital. Patients were excluded if they have had any past experience with chemotherapy, were ineligible to receive anti-emetic therapy and/or denied anti-emetic therapy for any reason.
Statistics Statistical analysis for primary outcome was performed using Fisher’s exact test. The total compliance rate was calculated by the total number of patients being treated appropriately divided by the total number of patients being treated. Comparative secondary analyses measuring variant compliance outcomes studied patients being appropriately under- and over-treated. Analyses for measuring which subgroup had the least compliance and the most compliance were done comparing the total number of patients being appropriately treated in each subgroup.
Results Medical records from a total of 487 patients were recorded at Blount Memorial Hospital. In total, 70 patients were classified under high emetic risk, 292 patients were classified under moderate emetic risk, 60 patients were classified under low emetic risk, and 65 patients were classified under minimal emetic risk. Patient data were classified as receiving appropriate treatment if the patient received 5HT3-RA, steroid, and NK1-RA in the high emetic risk, 5HT3-RA and a steroid in the moderate emetic risk (plus or minus NK1-RA), steroid/dopamine antagonist/piperazine anti-emetic in the low emetic risk, and no anti-emetic agent in the minimal emetic risk category. Overall, 63% of patients received appropriate antiemetic prophylaxis among all subgroups. Patients in the
350 300
N receiving appropriate treatment
250
total N
200 150 100 50 0 High
Moderate
Low
Minimal
Figure 1. Categorical comparison of the total population of high-, moderate-, low- and minimal-risk patients vs. the respective populations administered appropriate anti-emetic prophylaxis.
moderate-risk category were most likely (90%) and patients in the high-risk (34%) and low-risk (6.7%) categories were least likely to receive appropriate antiemetic prophylaxis medications. This was confirmed with Chi-square analysis and was statistically significant with a p value of 0.0001. In the moderate-risk category, 260 of 292 patients (90%) received appropriate chemotherapy, 24 of 70 patients (34%) in the high-risk category received appropriate chemotherapy, 4 of 60 (7%) patients in the low-risk category, and 18 of 65 (28%) patients in the minimal-risk category received appropriate chemotherapy (Figure 1). Patients in the high emetic risk category are least likely to receive all the appropriate anti-emetic agents, with 46 of 70 (66%) patients not receiving a NK1-RA. In the low emetic risk category, only 4 of the 60 patients (7%) were treated appropriately, with majority of patients (n ¼ 56) receiving a combination regimen, usually with a 5HT3-RA and a steroid. Patients in the minimal emetic risk category are also likely to receive unnecessary anti-emetic agents—47 of 65 patients (72%) receiving some type of routine anti-emetic prophylaxis. Patients in the minimal-risk category were most likely to receive either a 5HT3-RA or a steroid as the unnecessary anti-emetic agent—both agents being given to 37 of 65 patients (57%). When looking at the appropriate doses for antiemetic agents, patients in the moderate-risk category were most likely to be treated with appropriate guideline-based anti-emetic dose. In total, 226 patients of the 487 total patients (46%) were given appropriate doses of anti-emetic agents and 169 patients (34% of total population) were from the moderate-risk category. Dexamethasone was the most likely agent to be given with an inappropriate dose with doses >12 mg given to 192 patients of 490 patients (39%).
Downloaded from opp.sagepub.com by guest on November 16, 2015
4
Journal of Oncology Pharmacy Practice 0(0) Conflict of interest
Discussion and conclusion
None declared.
Health care providers are more likely to be compliant with the NCCN guidelines if using moderate emesis risk chemotherapy. Patients receiving high emesis risk chemotherapy are often not given aprepitant, even if they are given a serotonin antagonist and a steroid, which is reflected as low compliance with guidelines. Patients receiving minimal emesis risk chemotherapy are often given a serotonin antagonist or steroid without any additional indication when no routine prophylaxis is needed. Although low-risk category patients received at least one of the guideline appropriate medications, they were still listed as being noncompliant due to the use of combination therapy in a majority of patients. Patients in all risk categories are often given a steroid dose higher than the NCCN indicated dose. Problems with this study include the limited patient population, lack of regional variance, and frequent updates with the NCCN anti-emesis guidelines. While frequently updating NCCN guidelines ensures up-todate information being passed on to clinicians, it impedes studying compliance over a period of time. Limiting patients to one hospital reduces external validity as the data from this study cannot reliably be extrapolated to another setting. In conclusion, patients receiving moderate emetic risk chemotherapy are most likely to receive prophylaxis anti-emetic agents. This would mean that patients in this category are also most likely to receive relief from CINV, which should reduce their morbidity. Reducing CINV in patients should also improve compliance in patients who are likely to delay or withdraw from treatment due to adverse events. While compliance is poor in the minimal emetic risk category, the patients are getting unnecessary anti-emetic agents and while this does not affect morbidity in patients due to CINV, it causes additional costs to both the patient and the hospital. Compliance in the high emetic risk category is poor due to patients not always getting a NK1-RA, this can result in significant morbidity in patients if they exhibit delayed CINV. Since morbidity in patients due to adverse events can reduce chemotherapy treatment compliance with patients or even cause patients to withdraw completely from chemotherapy treatment. This in turn can cause the patient significant harm, both from CINV and patient noncompliance. Health care providers should be re-educated on the importance of being compliant with anti-emetic prophylaxis—especially for patients receiving high emetic risk chemotherapy.
Disclaimer No animals or plants were harmed in the pursuance of this study.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Acknowledgements This study was conducted at Maryville, TN. Statistics were Dr Shaun Rowe, PharmD, University of Tennessee Health
Blount Memorial Hospital, performed with the help of associate professor at the Science Center.
References 1. NCCN Clinical Practice Guidelines in anti-emesis. Version 1.2013. 2. Jordan K, Sippel C and Schmoll HJ. Guidelines for antiemetic treatment of chemotherapy-induced nausea and vomiting: past, present, and future recommendations. Oncologist 2007; 12: 1143–1150. 3. Laslo J. Emesis as limiting toxicity in cancer chemotherapy. In: Lazlo J (ed.) Antiemetics and cancer chemotherapy. Baltimore, Maryland: Williams & Wilkins, 1993, pp.1–5. 4. Grunberg SM, Deuson RR, Marvos P, et al. Incidence of chemotherapy induced nausea and emesis after modern anti emetics. Cancer 2004; 100: 2261–2268. 5. Richardson JL, Marks G and Levine A. The influence of symptoms of disease and side effects on compliance with cancer. J Clin Oncol 1988; 6: 1746–1752. 6. Mitchell EP. Gastrointestinal toxicity of chemotherapeutic agents. Simin Oncol 1992; 19: 566–579. 7. Hesketh PJ, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997; 103–109. 8. Hesketh PJ and Gandara DR. Serotonin antagonists: a new class of antiemetic agents. J Natl Cancer Inst 1991; 83: 613–620. 9. Andrews PL, Bjandari P, Darvey PT, et al. Are all 5HT3 receptor antagonists the same? Eur J Cancer 1992; 28 (A Suppl 1): 2–6. 10. Leonard MC and Militello ML. 5-HT3 receptor antagonists and ECG changes. Cleve Clin J Med 2002; 5: 2–2. 11. Aapro MS. Palonosetron as an antiemetic and anti nausea agent in oncology. Ther Clin Risk Manag 2007; 3: 1009–1020. 12. Vardy J, Chiew KS, Galica J, et al. Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy. Br J Cancer 2006; 94: 1011–1015. 13. Hesketh PJ, Grunburg SM, Gralla RJ, et al. The oral neurokinin 1 antagonist aprepitant for the prevention of
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Daniel and Waddell
5
chemotherapy induced nausea and vomiting. Multinational, randomized, double blind, placebo controlled trial in patients receiving high dose Cisplatin – the aprepitant protocoll 052 study group. J Clin Oncol 2003; 21: 4112–4119.
14. Stoutenburg JP and Raftopoulos H. Antiemetic studies on the NK1 receptor antagonist aprepitant. J Natl Compr Canc Netw 2004; 2: 491–497.
Downloaded from opp.sagepub.com by guest on November 16, 2015
Oncology Pharmacy Practice
Original Article
Compliance with National Comprehensive Cancer Network anti-emesis guidelines in a Community Hospital Cancer Center
J Oncol Pharm Practice 0(0) 1–5 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1078155214546563 opp.sagepub.com
Divya Daniel1 and Aubrey Waddell2,3
Abstract Objective: Nausea and vomiting are common adverse events exhibited by patients receiving chemotherapy. Prophylactic use of anti-emetic agents has been shown to reduce chemotherapy-induced nausea and vomiting. Compliance with the National Comprehensive Cancer Network anti-emesis guidelines (Version 1.2013) by practitioners in a community out-patient hospital (Blount Memorial Hospital) has been reviewed and the results are presented herein. Design: Retrospective study of patients receiving their first cycle of chemotherapy. Patients: A total of 487 patients were reviewed from January 2005 to July 2012. In total, 70 patients were categorized in the high-risk category, 292 patients were categorized in the moderate-risk category, 60 patients were categorized in the low-risk category, and 65 patients were categorized in the minimal-risk category as per the National Comprehensive Cancer Network guidelines. Included patients were being administered the first cycle of their first treatment at Blount Memorial Hospital. Data: Data were collected retrospectively from patient chemotherapy dispensing folders. Results: In all, 63% of the patients received appropriate anti-emetic prophylaxis medications as per the National Comprehensive Cancer Network guidelines. Post-comparison between outcomes based on the risk category showed that patients in the moderate-risk category were most likely (91%) and patients in the low-risk category were least likely (6.67%) to receive appropriate anti-emetic prophylaxis as per the National Comprehensive Cancer Network guidelines. Conclusion: Overall compliance with guidelines is acceptable. Patients in the moderate risk category are most likely to receive appropriate anti-emetic prophylaxis.
Keywords National Comprehensive Cancer Network, compliance, community hospital, anti-emesis
Introduction Chemotherapy-induced nausea and vomiting (CINV) is the one of the most common and historically feared side effects of chemotherapy.1 Prior to research leading to protocols detailing the proper use of anti-emetic agents for prophylaxis of CINV and the introduction of modern anti-emetics like 5-HT3 receptor antagonist (5HT3-RA), many patients avoided or delayed certain chemotherapy due to CINV.2 In addition to decreasing compliance with chemotherapy, CINV can also lead to other complications such as metabolic imbalances, anorexia, poor nutritional support.1,3 The combined morbidity caused by CINV has caused patients to
withdraw from potentially useful or curative chemotherapy. Appropriate use of anti-emetic agents has been shown to reduce or eliminate CINV in
1
2, University of Tennessee Health Science Center, College of Pharmacy, Knoxville, TN, USA 2 2, University of Tennessee Health Science Center, College of Pharmacy, Maryville TN, USA 3 2, Blount Memorial Hospital, Maryville TN, USA Corresponding author: Divya Daniel, University of Tennessee Health Science Center, College of Pharmacy, C/O 2014, 317 Mayhurst Lane, Cordova, TN 38018, USA. Email: [email protected]
Downloaded from opp.sagepub.com by guest on November 16, 2015
2
Journal of Oncology Pharmacy Practice 0(0)
approximately 70–80% of patients.4 Controlling adverse events in patients may positively impact patient compliance and, thus, decrease oncology patient morbidity.5 Guidelines serve as useful tools for practitioners to appropriately implement and integrate the latest clinical research into their practice.1 The National Comprehensive Cancer Network (NCCN) provides guidelines for practitioners to improve the quality and effectiveness of cancer care in oncology patients.6 The NCCN anti-emesis guidelines provide an overview of treatment to prevent CINV in patients receiving chemotherapy and are often used by practitioners in community oncology hospitals to set the standard of practice.2 Both the likelihood and severity of CINV vary dependent upon the chemotherapy agent used.7 The emetogenic potential of chemotherapy agents is classified into four different subtypes by the NCCN: high emetic risk, moderate emetic risk, low emetic risk, and minimal emetic risk. High emetic risk induces emesis in greater than 90% of treated patients, moderate emetic risk induces emesis in 30–90% of treated patients, low emetic risk induces emesis in 10–30% of treated patients, and minimal emetic risk induces emesis in less than 10% of treated patients.8 All the agents in the high emetic risk group and some agents from the moderate emetic risk group have the propensity to cause both acute and delayed CINV.6 While the type of chemotherapy agent is the primary risk factor for CINV, patient-specific risk factors also play affect the incidence of CINV in patients.1,2 Patient-specific risk factors include female gender, young age, history of alcohol intake, experience with emesis during pregnancy, impaired quality of life, and previous experience with chemotherapy.2 The NCCN does not specifically include patient-specific risk factors into the anti-emesis guidelines, but instead advise practitioners to chose anti-emetic regimens based both on the highest emetic risk and patient-specific risk factors.1,2 CINV is also classified as acute, delayed, anticipatory, breakthrough, and refractory. Anti-emetic prophylaxis is especially useful in acute, delayed, and some breakthrough CINV. Commonly used regimens include 5-hydroxytryptamine 3 receptor antagonists (5HT3-RAs) and a steroid. If delayed emesis is anticipated, a neurokinin 1 receptor antagonist (NK1-RA) is used as well. 5HT3-RAs have been shown to be among the most effective anti-emetic agents in acute CINV.7 Their development in the early 1990s has allowed for significant advancements in CINV treatment.9 All the 5HT3-RAs have been shown to be effective treatments for CINV and appear to be interchangeable.10 The lowest effective dose of each 5HT3-RA should be utilized. Common adverse events associated with 5HT3RAs include headache, lightheadedness, and sedation.11
Electrocardiography (ECG) changes, including QT prolongation, are among the more serious adverse events that can be associated with 5HT3-RAs. Palonosetron also appears to be effective in delayed CINV.12 The most recent NCCN anti-emesis Version 1.2014 recommends using palonosetron as the preferred 5HT3-RA for high- and moderate-risk anti-emesis. However, the objective of this research includes data derived from a range of 5HT3-RAs and is based on NCCN anti-emesis Version 1.2013. Steroids effectively control CINV—more-so when combined with a 5HT3-RA.1,2 Dexamethasone is used in prophylaxis regimens for high, moderate, and low emetic risk chemotherapy patients exhibiting CINV. This is combined with NK1RA for patients exhibiting delayed CINV. Common adverse events associated with dexamethasone include hyperglycemia, water retention, insomnia, and gastric discomfort.13 NK1-RA, aprepitant, prevents CINV, centrally in the brain stem and peripherally in the gastrointestinal tract, and is very effective in preventing delayed CINV.14 Adverse events associated with aprepitant include headache and fatigue. The NCCN guidelines Version 1.2013 recommends the use of a 5HT3-RA + steroid + NK1-RA for prophylaxis of high-risk anti-emesis, a 5HT3-RA + steroid (NK1RA) for prophylaxis of moderate-risk anti-emesis, steroid/piperazine anti-emetic/dopamine antagonist/ benzodiazepine for prophylaxis of low-risk anti-emesis, and no prophylactic emesis is recommended for minimal-risk anti-emetic. The primary goal of this project was to retrospectively measure oncologists’ compliance with the NCCN anti-emesis guidelines Version 1.2013 at the onset of a patient’s first chemotherapy cycle. Secondary objectives were to determine how many patients received higher/ lower than needed anti-emetic doses and their distribution within emesis risk categories.
Methods Study population Oncology patients from January 2005 to July 2012 were used in this study. Data were collected from patient chemotherapy dispensing folders and all patient-specific information was discarded—no patients and/or families were contacted. The study was approved by the Investigational Review boards of Blount Memorial Hospital and University of Tennessee Health Science Center, Knoxville Campus. Data were recorded during the first cycle of chemotherapy treatment. Included were chemotherapy agents used, whether or not an anti-emetic was prescribed prophylactically, and if so what anti-emetic agent was used.
Downloaded from opp.sagepub.com by guest on November 16, 2015
Daniel and Waddell
3
The NCCN guidelines were used to classify chemotherapy agents under high emetic risk, moderate emetic risk, low emetic risk, or minimal emetic risk category. We did not include patient-specific risk factors while classifying risk status. Patients received all prophylactic anti-emetic medications in the hospital if they were in-patients, or in the out-patient clinic if they were out-patients. When evaluating multiple day chemotherapy regimens, compliance was based on prophylaxis on day 1, since patients were evaluated on a daily basis. For the determination of inappropriate dosage, dexamethasone doses greater than 12 mg or the administration of non-NCCN recommended drug for anti-emesis prophylaxis was considered inappropriate. The inclusion criteria of this study were patients diagnosed with cancer and received at least their first cycle of chemotherapy between January 2005 and July 2012 at Blount Memorial Hospital. Patients were excluded if they have had any past experience with chemotherapy, were ineligible to receive anti-emetic therapy and/or denied anti-emetic therapy for any reason.
Statistics Statistical analysis for primary outcome was performed using Fisher’s exact test. The total compliance rate was calculated by the total number of patients being treated appropriately divided by the total number of patients being treated. Comparative secondary analyses measuring variant compliance outcomes studied patients being appropriately under- and over-treated. Analyses for measuring which subgroup had the least compliance and the most compliance were done comparing the total number of patients being appropriately treated in each subgroup.
Results Medical records from a total of 487 patients were recorded at Blount Memorial Hospital. In total, 70 patients were classified under high emetic risk, 292 patients were classified under moderate emetic risk, 60 patients were classified under low emetic risk, and 65 patients were classified under minimal emetic risk. Patient data were classified as receiving appropriate treatment if the patient received 5HT3-RA, steroid, and NK1-RA in the high emetic risk, 5HT3-RA and a steroid in the moderate emetic risk (plus or minus NK1-RA), steroid/dopamine antagonist/piperazine anti-emetic in the low emetic risk, and no anti-emetic agent in the minimal emetic risk category. Overall, 63% of patients received appropriate antiemetic prophylaxis among all subgroups. Patients in the
350 300
N receiving appropriate treatment
250
total N
200 150 100 50 0 High
Moderate
Low
Minimal
Figure 1. Categorical comparison of the total population of high-, moderate-, low- and minimal-risk patients vs. the respective populations administered appropriate anti-emetic prophylaxis.
moderate-risk category were most likely (90%) and patients in the high-risk (34%) and low-risk (6.7%) categories were least likely to receive appropriate antiemetic prophylaxis medications. This was confirmed with Chi-square analysis and was statistically significant with a p value of 0.0001. In the moderate-risk category, 260 of 292 patients (90%) received appropriate chemotherapy, 24 of 70 patients (34%) in the high-risk category received appropriate chemotherapy, 4 of 60 (7%) patients in the low-risk category, and 18 of 65 (28%) patients in the minimal-risk category received appropriate chemotherapy (Figure 1). Patients in the high emetic risk category are least likely to receive all the appropriate anti-emetic agents, with 46 of 70 (66%) patients not receiving a NK1-RA. In the low emetic risk category, only 4 of the 60 patients (7%) were treated appropriately, with majority of patients (n ¼ 56) receiving a combination regimen, usually with a 5HT3-RA and a steroid. Patients in the minimal emetic risk category are also likely to receive unnecessary anti-emetic agents—47 of 65 patients (72%) receiving some type of routine anti-emetic prophylaxis. Patients in the minimal-risk category were most likely to receive either a 5HT3-RA or a steroid as the unnecessary anti-emetic agent—both agents being given to 37 of 65 patients (57%). When looking at the appropriate doses for antiemetic agents, patients in the moderate-risk category were most likely to be treated with appropriate guideline-based anti-emetic dose. In total, 226 patients of the 487 total patients (46%) were given appropriate doses of anti-emetic agents and 169 patients (34% of total population) were from the moderate-risk category. Dexamethasone was the most likely agent to be given with an inappropriate dose with doses >12 mg given to 192 patients of 490 patients (39%).
Downloaded from opp.sagepub.com by guest on November 16, 2015
4
Journal of Oncology Pharmacy Practice 0(0) Conflict of interest
Discussion and conclusion
None declared.
Health care providers are more likely to be compliant with the NCCN guidelines if using moderate emesis risk chemotherapy. Patients receiving high emesis risk chemotherapy are often not given aprepitant, even if they are given a serotonin antagonist and a steroid, which is reflected as low compliance with guidelines. Patients receiving minimal emesis risk chemotherapy are often given a serotonin antagonist or steroid without any additional indication when no routine prophylaxis is needed. Although low-risk category patients received at least one of the guideline appropriate medications, they were still listed as being noncompliant due to the use of combination therapy in a majority of patients. Patients in all risk categories are often given a steroid dose higher than the NCCN indicated dose. Problems with this study include the limited patient population, lack of regional variance, and frequent updates with the NCCN anti-emesis guidelines. While frequently updating NCCN guidelines ensures up-todate information being passed on to clinicians, it impedes studying compliance over a period of time. Limiting patients to one hospital reduces external validity as the data from this study cannot reliably be extrapolated to another setting. In conclusion, patients receiving moderate emetic risk chemotherapy are most likely to receive prophylaxis anti-emetic agents. This would mean that patients in this category are also most likely to receive relief from CINV, which should reduce their morbidity. Reducing CINV in patients should also improve compliance in patients who are likely to delay or withdraw from treatment due to adverse events. While compliance is poor in the minimal emetic risk category, the patients are getting unnecessary anti-emetic agents and while this does not affect morbidity in patients due to CINV, it causes additional costs to both the patient and the hospital. Compliance in the high emetic risk category is poor due to patients not always getting a NK1-RA, this can result in significant morbidity in patients if they exhibit delayed CINV. Since morbidity in patients due to adverse events can reduce chemotherapy treatment compliance with patients or even cause patients to withdraw completely from chemotherapy treatment. This in turn can cause the patient significant harm, both from CINV and patient noncompliance. Health care providers should be re-educated on the importance of being compliant with anti-emetic prophylaxis—especially for patients receiving high emetic risk chemotherapy.
Disclaimer No animals or plants were harmed in the pursuance of this study.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Acknowledgements This study was conducted at Maryville, TN. Statistics were Dr Shaun Rowe, PharmD, University of Tennessee Health
Blount Memorial Hospital, performed with the help of associate professor at the Science Center.
References 1. NCCN Clinical Practice Guidelines in anti-emesis. Version 1.2013. 2. Jordan K, Sippel C and Schmoll HJ. Guidelines for antiemetic treatment of chemotherapy-induced nausea and vomiting: past, present, and future recommendations. Oncologist 2007; 12: 1143–1150. 3. Laslo J. Emesis as limiting toxicity in cancer chemotherapy. In: Lazlo J (ed.) Antiemetics and cancer chemotherapy. Baltimore, Maryland: Williams & Wilkins, 1993, pp.1–5. 4. Grunberg SM, Deuson RR, Marvos P, et al. Incidence of chemotherapy induced nausea and emesis after modern anti emetics. Cancer 2004; 100: 2261–2268. 5. Richardson JL, Marks G and Levine A. The influence of symptoms of disease and side effects on compliance with cancer. J Clin Oncol 1988; 6: 1746–1752. 6. Mitchell EP. Gastrointestinal toxicity of chemotherapeutic agents. Simin Oncol 1992; 19: 566–579. 7. Hesketh PJ, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1997; 103–109. 8. Hesketh PJ and Gandara DR. Serotonin antagonists: a new class of antiemetic agents. J Natl Cancer Inst 1991; 83: 613–620. 9. Andrews PL, Bjandari P, Darvey PT, et al. Are all 5HT3 receptor antagonists the same? Eur J Cancer 1992; 28 (A Suppl 1): 2–6. 10. Leonard MC and Militello ML. 5-HT3 receptor antagonists and ECG changes. Cleve Clin J Med 2002; 5: 2–2. 11. Aapro MS. Palonosetron as an antiemetic and anti nausea agent in oncology. Ther Clin Risk Manag 2007; 3: 1009–1020. 12. Vardy J, Chiew KS, Galica J, et al. Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy. Br J Cancer 2006; 94: 1011–1015. 13. Hesketh PJ, Grunburg SM, Gralla RJ, et al. The oral neurokinin 1 antagonist aprepitant for the prevention of
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