Original Article

Adherence to antiemetic guidelines and control of chemotherapy-induced nausea and vomiting (CINV) in a large hospital

J Oncol Pharm Practice 2015, Vol. 21(3) 163–169 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1078155214524809 opp.sagepub.com

Fatima Caracuel, Nuria Mun˜oz, Ursula Ban˜os and Gabriel Ramirez

Abstract Purpose: The aim of the study was to determine the antiemetic prescription adherence both to the protocol of our hospital and to international recommendations, as well as to analyze the relationship between this adherence and the incidence of nausea and vomiting (NV) and between the adherence and patients’ individual risk. Methods: This is a four-month observational study which included antiemetic prescriptions for adult cancer patients. Prescriptions were considered adherent or not to hospital protocol and also to international guidelines. Patients were given a form to record the NV they suffered and this was to be returned at their next appointment. Results: A total of 102 prescriptions were analyzed. Taking into account the hospital protocol, 59% and 54% were correct (acute and delayed phase, respectively). Of those considered outside the protocol, 24% and 13% did follow international guidelines. In the delayed phase, complete response was achieved in 76% and 72% of the patients, with compliant and non-compliant prescriptions, respectively (82% and 90% in the acute phase). Adherence to the hospital protocol was higher in patients under 50 years old (p ¼ 0.015) and in those without previous experience of NV (p ¼ 0.010). Adherence to international guidelines was higher in female patients (p ¼ 0.023). Conclusion: Our study confirms low adherence with both local and international recommendations for antiemetic prescriptions. However, we could not prove that adherence involves a CINV reduction. Adherence did not seem to be influenced by the doctor’s perception of the patient’s risk of emesis.

Keywords Antiemetics, CINV, guidelines, adherence, protocols, prescription

Introduction Despite the application of the latest antiemetic recommendations, chemotherapy patients are still suffering from nausea and vomiting (NV).1,2 Consequences include a decrease in patients’ quality of life, causing even change of the chemotherapy (CT) regime, as well as a decrease in the effectiveness of oral treatment. The problem acquires greater importance if it is not perceived in the same way by patients and health professionals. A study noted that the concordance between the concerns of patients and the perception by doctors and nurses was around 0.6.3 Patients’ risk of emesis is determined by the emetogenic potential of antineoplastic agents they receive and also their individual characteristics. Although the

former tends to be taken into account when choosing the antiemetic regimen, it is usual not to assess the overall risk to the patient.4 Recently, several clinical guidelines with recommendations for the use of antiemetics were published by the Multinational Association of Support Care Cancer (MASCC), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN).5–7 However, despite these guidelines, some studies show that there is wide variation Hospital Virgen Macarena, Seville, Spain Corresponding author: Fatima Caracuel, Hospital Virgen Macarena, Avda dr Fedriani, Seville 41009, Spain. Email: [email protected]

164 in the prescription of antiemesis.8–10 There are even times when prescription is not clear, so nurses are the ones who must decide the regime. A study showed 47.8% of the prescription sheets did not properly fully indicate antiemesis details (drug, dose, and pattern).11 Published studies analyze the compliance of prescriptions to international or local recommendations, but none take both into account. Most of them do not differentiate the acute and the delayed phase nor if patients complied with the prescribed treatment, essential to achieve the objective. Therefore, we are faced with a situation where we have effective drugs for the prevention of CT-induced nausea and vomiting (CINV), but total control is not yet fully achieved. There is no uniformity in prescriptions, sometimes because of the absence of prescription, and other times because of an excess in prescription, exposing patients to drugs that they do not need, as well as unnecessarily increasing health spending. The aim of the study was to determine the antiemetic prescription adherence both to the protocol of our hospital and to international recommendations, as well as to analyze the relationship between this adherence and the incidence of NV and between the adherence and the patients’ individual risk to emesis.

Methods This is a four-month observational study at the Oncology Day Unit of a large tertiary hospital. This is an adult infusion unit for outpatients.

Population studied We included prescriptions for adult patients with a new cycle of CT (regardless of the line of treatment). Patients with very low emetic risk of CT and those whose treatment included a corticoid were excluded.

Antiemetic protocol Public hospitals in Spain provide all the medication necessary for the control of NV, including acute and delayed phases. Acute phase is defined as occurring in the first 24 h after CT (day 1). Delayed emesis refers to that which appears 24 h after ending treatment and may last several days.6 In our hospital’s antiemesis protocol, antineoplastic agents are grouped according to the scheme drawn up by Hesketh (five emetogenicity levels):12 very low, low, moderate, high and very high (dose of cisplatin 70 mg/m2). Then there are three types of medication: type 1 (aprepitant days 1–3 + granisetron day 1 + dexamethasone days 1–4, recommended for a

Journal of Oncology Pharmacy Practice 21(3) dose of cisplatin  70 mg/m2 or refractory to type 2), type 2 (for moderate or high risk: methylprednisolone day 1 + granisetron days 1–3 + dexamethasone days 2–4), and type 3 (metoclopramide IV day 1 + dexamethasone day 1 + metoclopramide orally the following days prn, for low risk). On day 1, the administration was done by nurses and the other days at home. In cases in which the CT lasts several consecutive days, and in conformity with ASCO recommendations, acute phase was deemed on each day of the CT administration and delayed phase as from 2 days thereafter.6 For schemes with associations of two or more cytostatics, we considered the agent with the highest degree of risk of emesis.6 The antiemetic regime for patients receiving combination chemoradiotherapy is dictated by the emetogenicity of CT, unless the emetic risk of radiation therapy is higher. There are some differences between the local guideline and the international recommendations published on the date of the study (ASCO 2006, MASCC 2006, NCCN 2007).5–7 The main difference is that guides include aprepitant and for combination anthracyclinecyclophosphamide (AC and EC).

Outcome Adherence to recommendations was measured. Prescriptions were considered compliant or not to Hospital Protocol (HP). Prescriptions that were not adjusted to the HP were evaluated as compliant or not to the International Guidelines (IG). Inappropriate prescription was defined as any difference in the medicines, doses, route, or dosage interval prescribed. In cases in which the patient had suffered vomiting in a previous cycle, the next highest regimen of antiemesis was to be chosen. Complete response to antiemetics was defined as no vomiting and no rescue treatment (after antineoplastic therapy and during the five following days). Absence or presence of nausea was also registered. It was considered that the patient was compliant to their antiemetic treatment when they took at least 80% (more than one pill) of the medication prescribed to take at home. Regarding the patients’ individual characteristics, we considered those that increase the risk of emesis: sex (female), age ( 50 years old old Women Men Low Moderate High Very high Yes Percentage of adherent 77 prescriptions (N¼102)










Alcohol consumption (%) p ¼ 0.395

Previous experience of NV (%) p ¼ 0.010

Personal attitude (%) p ¼ 0.280





Negative Optimistic Yes











Percentage of adherent 58 prescriptions (N ¼ 102)


Nervousness (%) p ¼ 0.887



Constipation (%) p ¼ 0.366

HP: hospital protocol; CT: chemotherapy; NV: nausea and vomiting.

Only two studies differentiated adherence to recommendations between acute and delayed phase and took into account the patients’ compliance taking the medication. Compliance here was 68% and 85%.19,21 Our patients, whose compliance with treatment was lower (61%), had slightly less protection than these studies. Since adherence to protocols is higher in both patients with favorable and unfavorable prognosis (age and previous experience of NV) and, moreover, differences exist in few variables, adherence did not seem to be influenced by the doctor’s perception of the patient’s risk of emesis. We did not find studies about the relationship between the individual patients’ risk and the adherence to protocols. Although it is known that patients’ characteristics also influence the incidence of NV, international practice guidelines

do not account for individual variation among patients.6 This study includes a complete analysis of the prescription of antiemetic treatment. Also studying adherence to international recommendations has allowed us to categorize a prescription as correct, even if it did not meet the HP. Our study also analyzes the relationship between the adherence to protocols and the absence of CINV and between the individual patients’ characteristics and adherence, and has broken down the adherence according to the phase of emesis and the patients’ compliance with the prescribed treatment. However, this study has some limitations. Hospitalized patients have not been included, so the conclusions cannot be extrapolated to that situation in which patients have a better response to antiemetic prophylaxis than those

168 who receive treatment at the Day Unit.22 The patient population was heterogeneous, but in accordance with the real population at the Day Unit. The fact that part of the form should be filled out by patients outside the hospital caused its loss in some cases. In conclusion, our study confirms low adherence with both local and international recommendations for antiemetic prescription. However, we could not prove that the adherence involves an improvement to complete response. Adherence did not seem to be influenced by the doctor’s perception of the patient’s risk of emesis. Studies are often focused on the implementation of clinical practice guidelines, although it is known that antiemesis management is complex and includes interventions that also include dietary and psychological aspects, and not only medication. However, the implementation of prescription guides facilitates decision-making to physicians. Although there are some differences between the most important IG, all of them are based on evidence from recent clinical trials. Thus, the low adherence to them is a worrying fact that makes patients not receive the most appropriate medication to their CT. The reasons may be related to the guide itself, to the way in which it is implemented or to the physician’s perceived drug efficacy and drug side-effect profiles.9 Some papers propose possible ways of intervention to decrease the variability in the prescription of antiemetic prophylaxis including: dissemination of updated clinical practice guidelines, interdisciplinary committees, educational outreach visits by opinion leaders, standardized antiemetic protocols included in order forms (or a computerised decision-support system), pharmacist validation and, the most effective one, providing feedback to clinicians on the CINV patient’s response.8–10,23–25 Acknowledgements The authors thank Beatriz Puche Valdayo and Chris Mott for their reading and advice to prepare this manuscript, Juan Polo for his help with statistical analysis and nursing and medical staff for their collaboration and care of the patients.

Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest None declared.

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Adherence to antiemetic guidelines and control of chemotherapy-induced nausea and vomiting (CINV) in a large hospital.

The aim of the study was to determine the antiemetic prescription adherence both to the protocol of our hospital and to international recommendations,...
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