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Year : 2021  |  Volume : 4  |  Issue : 1  |  Page : 33-39

Monitoring the adherence to an adapted evidence-based clinical practice guideline on antiemetics in 669 patients with cancer receiving 1451 chemotherapy doses at a University oncology center in Saudi Arabia

1 Clinical Pharmacy Unit, Pharmacy Services Department, King Khalid University Hospital, King Saud University Medical City; University Oncology Center, King Saud University Medical City, Riyadh, Saudi Arabia
2 Clinical Practice Guidelines Unit, Quality Management Department, King Khalid University Hospital, King Saud University Medical City; Research Chair for Evidence-Based Health Care and Knowledge Translation, King Saud University, Riyadh, Saudi Arabia
3 University Oncology Center, King Saud University Medical City; Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia

Date of Submission28-Jun-2020
Date of Decision29-Jul-2020
Date of Acceptance15-Aug-2020
Date of Web Publication06-Jan-2021

Correspondence Address:
Haya Fahad Al-Salloum
Department of Pharmacy, King Saud University Hospital Medical City, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JNSM.JNSM_10_20

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Objectives: Chemotherapy-induced nausea and vomiting (CINV) is a common medication safety issue among cancer patients worldwide. However, there remains a research gap on adherence to the clinical practice guidelines (CPGs) for antiemetic medications to prevent and treat CINV in Saudi Arabia. Further, the adherence to our center's CPG for antiemetics for CINV at our center was never quantified before. Therefore, this audit was designed as an implementation and quality improvement intervention to fill the knowledge gaps. Methods: We conducted a retrospective cross-sectional observational study of the adult cancer patients attending the University Oncology Center at King Saud University Medical City. Data were extracted from the electronic health records' database for patients receiving chemotherapy in the months of February and November 2017. Results: Among the 669 adult cancer patients who received 1451 chemotherapy doses at our center, nearly 48% of the antiemetic prescriptions adhered to our adopted CPG's recommendations. The adherence of prescribers was more likely to moderate emetogenic agents such as doxorubicin and ifosfamide as compared to the high emetogenic agents such as cisplatin and cyclophosphamide >1500 mg/m2. Conclusions: Adherence to the antiemetics for CINV-CPG was suboptimal due to the unavailability of neurokinin1-receptor antagonists (NK1) antagonists and the lack of knowledge by prescribers. NK1 antagonists should be available to maximize the level of cancer care. Regular physician's education and training sessions must be conducted to familiarize them with the CPG evidence-based recommendations.

Keywords: Adherence, antiemetic, chemotherapy, practice guideline

How to cite this article:
Al-Salloum HF, Amer YS, Alsaleh KA. Monitoring the adherence to an adapted evidence-based clinical practice guideline on antiemetics in 669 patients with cancer receiving 1451 chemotherapy doses at a University oncology center in Saudi Arabia. J Nat Sci Med 2021;4:33-9

How to cite this URL:
Al-Salloum HF, Amer YS, Alsaleh KA. Monitoring the adherence to an adapted evidence-based clinical practice guideline on antiemetics in 669 patients with cancer receiving 1451 chemotherapy doses at a University oncology center in Saudi Arabia. J Nat Sci Med [serial online] 2021 [cited 2022 Aug 13];4:33-9. Available from: https://www.jnsmonline.org/text.asp?2021/4/1/33/306255

  Introduction Top

Cancer-chemotherapy induced nausea and vomiting is a common side effect which can compromise the quality of life of cancer patients and their compliance. Although with the advent of new treatment regimens, the prevalence of chemotherapy-induced nausea and vomiting (CINV) has markedly reduced, yet it remains one of the most distressing side effects for patients, where studies show the sizeable number of cancer patients consider either stopping or delaying future chemotherapy to avoid experiencing further CINV.[1],[2]

Oncologists, hematologists, and other members of the health-care teams must recognize the significance of CINV from patient-perspective, devising ways, and means to prevent it. Prescribers should review the emetogenic potential of each treatment regimen according to the updated published evidence in an endeavor to minimize or eliminate CINV. It is also important to individualize the assessment of CINV risk throughout the treatment cycles to address the appropriate timing of antiemetic agents. Recent studies showed that after almost 40 years of success and improvement in managing cancer, CINV remains a significant side effect that, if left unmanaged leads to a 60%–80% refusal rate of patients to continue chemotherapy.[3],[4]

Several specialized professional bodies have released clinical practice guidelines (CPGs) for the management of emesis resulting from chemotherapy, to wit: National Comprehensive Cancer Network (NCCN), Multinational Association for Supportive Care in Cancer (MASCC), European Society for Medical Oncology, American Society of Clinical Oncology (ASCO), and Oncology Nursing Society.[5],[6]

CINV risk factors are either patient-specific or treatment-specific, where some patient-specific risk factors cannot be controlled, such as the female gender, history of morning sickness, and young patients.[7],[8],[9] Treatment-specific risk factors include the chemotherapy emetogenicity, dose, and the schedule of each agent for combination protocols. A drug's tendency to cause nausea and/or vomiting is called “Emetogenicity.”[10],[11] The emetogenicity scale proposed in 1997 by Hesketh et al. divided chemotherapy agents and their doses into five levels based on their likelihood to cause CINV.[11],[12]

ASCO and NCCN further modified that most widely used scale into: (i) Highly emetogenic including agents or doses that cause CINV in >90% of patients, (ii) Moderately emetogenic including agents that induce CINV in 30%–90% of patients, (iii) Low emetogenic including medications that are associated with CINV rates of 10%–30%, and (iv) Minimal emetogenic including drugs that are associated with CINV rates of >10%.

We adapted a CPG for antiemetic regimens for CINV by ASCO to fit our local context using a formal CPG adaptation methodology titled the ”KSU-Modified-ADAPTE.” This method includes three phases, namely: set-up, adaptation, and finalization.[13] We adopt all of the recommendations from the ASCO-CPG after quality assessment through the Appraisal of Guidelines for Research and Evaluation Instrument (AGREE II) and considering their acceptability and applicability.[13],[14],[15]

Several implementation interventions were conducted at our center including; (i) leadership support via a memorandum from the director of the oncology center to comply with its recommendations, (ii) dissemination by posting the CPG full document including a list of implementation tools[13] over the intranet, in addition to a printed copy available from nursing stations, (iii) regular training sessions for physicians including oncologists and hematologists, and nurses of the center by the clinical pharmacist-lead of the project, (iv) the recommended medications were built as computerized provider order entry within the premedication order set in the hospital's newly launched electronic health records (EHRs) system, and (v) networking with existing projects by aligning with the center's strategic institutional and quality improvement plan.

We hypothesized that adherence to the clinical practice guidelines (CPGs) for antiemetic medications to prevent and treat CINV in Saudi Arabia is suboptimal. Audit and feedback were one of the major CPG implementation interventions adopted at our organization.[13] Therefore, this audit was conducted to evaluate the adherence to the CPG for antiemetic regimens for CINV, as a part of the continuous quality improvement and safety initiatives at our oncology center.

  Methods Top

The CPG was officially approved for implementation in late 2015. It was later reviewed and updated in 2017 with the updated source CPG, which required no changes in the recommendations.[14],[15] Based on the classification of chemotherapy drugs from the adapted CPG, a retrospective data collection was conducted to assess adherence to the CPGs. We adapted and used the antiemetics' recommendations from the ASCO-CPG to assess adherence to drugs, dosing, frequency, and duration.[14],[15] A closed medical record review was carried out by trained researchers to audit the adherence of physicians to the ASCO recommendations.

Adherence to the CPG recommendations was assessed in three point-of-care at our Oncology center including; (i) Medical oncology daycare “'MODC,” (ii) Male ward, and (iii) Female ward, where a total of 699 patients received 1451 chemotherapy doses during the study period. We assessed the chemotherapy drugs and/or combinations of drugs classified according to their “emetogenicity” potential risk, followed by the adherence of prescribers to the implemented CPG.

Study setting

This study was conducted at a university oncology center, which is a 100-bed tertiary care facility in the central region of Riyadh, Saudi Arabia. The center went operational in 2015 with five main units: (i) Adult oncology, (ii) Adult hematology and bone marrow transplantation, (iii) Pediatric oncology, (iv) Radiation oncology, and (v) Palliative care services. The center accepts approximately 150 new oncology cases every year and is currently treating >1000 patients.

Study design and subjects

This is a cross-sectional retrospective observational study among adults with cancer who visited the oncology center during the period from February 1 to 28, and from November 1to 30, 2017. Data were extracted from the EHRs database. The eligibility criteria included all adult people with cancer aged 15 years or older who were admitted for their chemotherapy treatment of any cycle during the study period.

Chemotherapy regimens were classified into low, moderate, and high emetogenic chemotherapy (LEC, MEC, and HEC, respectively), as shown in [Table 1]. The level of emetogenicity of combined chemotherapy agents was determined based on the ASCO-CPG recommendations. Per these guidelines, the antiemetic regimen used was labeled as appropriate or inadequate for each chemotherapeutic regimen used. Additional clinical algorithms that conform to the adapted CPG were utilized from NCCN-CPG.[7],[10]
Table 1: The distribution of chemotherapy according to emetogenic potential

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[Table 2] shows doses of antiemetic regimens that should fall within the therapeutic ranges of chemotherapy to be considered as appropriate antiemetic prophylaxis. All of the current CPGs for CINV mandate the use of combination-therapy for HEC regimens, which includes any of the selective serotonin receptor antagonists (5-hydroxytryptamine-3 [5-HT3] antagonist) plus dexamethasone plus a neurokinin-1 (NK1) receptor antagonist. For LEC regimens, however, the use of a 5-HT3 antagonist, dexamethasone, or a dopamine antagonist alone was considered as appropriate antiemetic prophylaxis in this study.
Table 2: Antiemetic dosing by chemotherapy emetogenic risk category

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The data points obtained from the EHRs were age, gender, diagnosis, chemotherapy protocol, and prophylactic antiemetic regimen prescribed. Simple frequencies were calculated for the doses prescribed by physicians. The Institutional Review Board (IRB) of the College of Medicine, King Saud University, approved the study with IRB number E-19-4179.

  Results Top

Our cohort consisted of 699 patients with the mean age of 31 (18–80) years, mainly including colorectal cancer patients (35.3%) and breast cancer patients (26.8%), [Table 3]. Patients received a total of 1451 chemotherapy doses. We calculated the percentage of adherence to the adapted CPG, as shown in [Table 4]. The antiemetics prescribed included 1899 doses. Serotonin (5-HT3) receptor antagonist contributed to 68.6% of the chemotherapy doses, while 18.47% doses were without the 5HT3 antagonist. Sixty-two percent of the chemotherapy doses were given with dexamethasone, and 11.09% without. [Table 1] shows the distribution of chemotherapy according to the emetogenic potential where a majority of chemotherapy prescriptions were classified as “Minimal Emetic Risk Chemotherapy” (MinEC) regimens (n = 447, 30.8%).
Table 3: Patient demographics

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Table 4: Overview of the antiemetic used per chemotherapy and patients

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Regarding the prevention of delayed nausea and vomiting, our data displayed 90% of prechemotherapy antiemetic prescriptions, not adhering to our center's adopted CPG. Most of the non-adherence manifested as an overuse per the ASCO 2013 guideline where it states not to give patients starting a chemotherapy regimen with low or moderate emetic risk or vomiting.[16] Overuse of ondansetron was observed in 68% of prescriptions [Table 4]. Nonadherence included both underuse and overuse of indicated antiemetic medications [Table 5].
Table 5: Percentage of prescriber's adherence to the adapted American Society of Clinical Oncology guideline

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[Table 6] shows ondansetron and granisetron (5-HT3 receptor antagonists) therapies in 9.8% and 15.46% of the patients treated with MinEC and LEC, respectively. None of the patients treated with HEC received NK1 receptor antagonists owing to the unavailability of this treatment choice in our facility during the study period; hence, we cannot judge it as nonadherence to the CPG.
Table 6: Percentage of antiemetic therapies used per chemotherapy emetogenic risk

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  Discussion Top

The current cross-sectional retrospective study is the first-of-its-kind to be conducted for the audit and feedback on the adherence to the recommendations of an adapted CPG from ASCO for antiemetics for CINV. The patterns of antiemetic medications prescribed for prophylaxis of CINV and their efficacy in patients undergoing chemotherapy was also studied.

Our facility being a nonprofit public university oncology center, provides antiemetic medications used for the prevention of CINV free of charge for eligible patients. Therefore, the Medications' cost and the clinicians' trends to prescribe treatment were not confounding factors influencing the antiemetic prescribing patterns in our setting. The study showed that adherence to the adapted ASCO-CPG was very low, especially in HEC regimens, as all patients have not received the NK1 antagonists before their chemotherapy as part of their premedication.

Management of the CINV adverse events reduces morbidity and increases patients' compliance with the chemotherapy treatment. The goal of our antiemetic CPG was complete prevention of CINV rather than this treatment. This goal is achievable in most of the patients receiving chemotherapy, including the highly emetogenic agents, to improve quality of life and avoid complications.

Similar studies to explore the implementation of different CINV-CPGs in variable health-care settings were conducted, where Aapro reported that adherence to the CPGs increased CINV control for both high and moderately emetogenic chemotherapy agents.[17] The updated ASCO-CPG recommended the triplet therapy with NK1-receptor antagonist (NK1-RA), a 5-HT3 receptor antagonist and dexamethasone for acute emesis originating from HEC regimens like anthracycline plus cyclophosphamide containing regimens.[6] Palonosetron, a potent 5-HT3 antagonist, and dexamethasone or the triplet therapy of 5-HT3 receptor antagonist, dexamethasone, and aprepitant are the ASCO-CPG recommended antiemetic modalities for MEC regimens.[13],[14] Dexamethasone monotherapy is recommended in LEC, while no prophylaxis is necessary for minimal emetogenic chemotherapy.[10] A combination of NK1-RA and dexamethasone is recommended for-delayed HEC emesis in the updated ASCO-CPG.[13] 5-HT3 receptor antagonist, dexamethasone, or NK1-RA is recommended for delayed-MEC regimens, while no prophylaxis for low and minimal emetogenic chemotherapy is required.[14],[15] Despite the antiemetic CPGs availability, adherence to the treatment recommendations is still less than optimal worldwide.

Steroids are subjected to misuse as antiemetic agents, where one study reported as high as 90% of antiemetic prescriptions containing dexamethasone did not adhere to the ASCO-CPGs in Saudi Arabia. Dexamethasone underuse was described in a previous study from Saudi Arabia; on the other hand, patients receiving prednisolone-containing chemotherapy was prescribed dexamethasone as antiemetic prophylaxis.[18]

In the current study, we noticed that 5-HT3 antagonist was prescribed as prechemotherapy prophylaxis and on discharge for delayed symptoms regardless of the emetogenicity of the chemotherapy. 5-HT3 receptor antagonists' overuse has been documented in a study from Brazil.[16] Ondansetron alone beyond 24 h has a minor role in the control of delayed CINV in patients who received HEC, where ondansetron monotherapy is less effective than dexamethasone. Furthermore, dexamethasone monotherapy for the management of delayed emesis was almost as effective as the use of 5-HT3 receptor antagonists beyond 24 h along with glucocorticoids. Accordingly, 5-HT3 receptor antagonists are not recommended to prevent delayed emesis.

While the ASCO-CPG suggested prophylactic dexamethasone for more than 24 h after chemotherapy as part of the triplet therapy for HEC or as monotherapy for LEC,[14],[15] the analysis of audit revealed none of our patients received dexamethasone on the day- 2 and 3 as prophylaxis for delayed emesis. This observed prophylactic dexamethasone underuse for delayed CINV is similar to the previous studies' observations.[18]

The lack of NK1-RA was a major hurdle in our patients' groups receiving HEC and MEC regimens, which might have contributed to the poor outcome of our patients' CINV. The introduction of NK1 receptor antagonists, could improve compliance with treatment guidelines and patients' outcomes. Furthermore, we expect that proper utilization of dexamethasone as recommended by the adapted ASCO-CPG could lead to greater control of CINV.

Our study showed suboptimal adherence to recommendations of the adapted CPG for CINV prophylaxis at our center. The major deviation from the 2017 ASCO clinical recommendations was the overuse of serotonin antagonists for the prophylaxis of LEC in acute CINV, and overuse of serotonin antagonists for prophylaxis of highly and moderately emetogenic in delayed CINV. For the highly emetogenic group, we found that almost all patients were managed inappropriately by receiving only a doublet regimen: a serotonin antagonist, and corticosteroids.

The lack of adherence to Day 1 regimen was primarily owing to the unavailability of a neurokinin antagonist during the study period. Our study showed frequent overuse of antiemetics for CINV prophylaxis, which could be clinically and economically relevant. Although our study was limited by its single-center and retrospective design, nonetheless we collected a large set of data.

Our results are consistent with the findings of Roila et al. who reported the adherence in 77 Italian centers.[18] Despite the modifications of the relevant CPGs and some of the prophylactic medications since 2000, patients remained nonadherent to antiemetic CPGs as they were either “under-treated” in acute prophylaxis in the high-risk group, or “over-treated” in acute and delayed prophylaxis in the moderate-, low-, and minimal-risk groups.[19]

Underuse of antiemetics predictably leads to patient complaints at follow-up visits, where such reports result in positive outcome measures like changing the prescription-practice of physicians. Since overuse can only be detected if patients without CINV are deliberately tapered to the minimally required dosage level to prevent this type of side effect, over-prescription of antiemetics is less likely to be detected by patients alone.

Evidence-based CPGs in general, or specifically our adapted version of CPG is a starting point, and a stepping stone on which case for the “individualized antiemetic regimen” could be built. An optimal patient's regimen includes both following the identified evidence-based CPG and the clinical judgment. Clinical judgments are based on a variety of factors, including (1) Clinical factors, for example, freedom from nausea and less use of rescue antiemetics, (2) Logistic factors, for example, the convenience of a regimen and likelihood of adherence,[6] and (3) Safety factors, for example potential agent's adverse effects consideration in certain situations.

Mansy et al. studied the prescription, effectiveness, and outcomes of antiemetics for CINV using the ASCO recommendations. The study revealed that patients who received antiemetics for CINV continued to experience the symptoms. In addition, his study observed that the improvement in controlling vomiting in the acute phase did not correspond to a similar improvement in the delayed phase.[4]

Strengths and limitations

Up to our knowledge, this is the first study to report the local implementation of evidence-based ASCO-CPGs for CINV antiemetics. Some of our study's limitations, however, are related to its quantitative, observational survey design, which hindered establishing or documenting the cause-effect relationship. Furthermore, NK1 (Aprepitant or Fosaprepitant) was unavailable in our center across the study period, rendering it unfair to categorize the HEC group as nonadherent to the adopted CPG. Patients' satisfaction follow-up for nausea and vomiting reporting posttreatment wasn't carried out, which is an area of investigation to effectively prevent and treat CINV.

  Conclusions Top

Adherence to the CPG is postulated to result in better control of CINV. We evaluated the patterns of prescription by physicians for prophylactic antiemetics in cancer patients during chemotherapy, as a part of the requirements for the CPG implementation audit and feedback. Despite the availability of the CINV antiemetic prophylaxis CPGs, this study indicated a low adherence rate. CPGs are important tools to support health-care quality and safety for cancer patients. Continuous and effective practical implementation strategies are needed to improve the quality of ongoing care for patients.

NK1 antagonists like aprepitant and fosaprepitant must be made available in the center formulary stock to reach a maximum level of patient care through adherence to our adopted CPG for antiemetics use in CINV.


  • Chemotherapy drugs administered for patients with cancer during November 2017
  • Overview of antiemetic been used per chemotherapy and patients
  • Percentage of antiemetic therapies used per the chemotherapy emetogenic risk and the prescriber's adherence to the adapted ASCO practice guidelines.


The authors wish to send their highest regards in acknowledgment, for the noted contributions of the clinical reviewers (Ahmad Abdel-Warith, Jawaher Ansari, Manal Abou Elkheir, Amani Hamad) and methodology reviewers (Lubna A. Al-Ansary, Hayfaa Wahbi, Shaikh Iqbal) during the CPG adaptation project. Moreover, the authors would like to thank the nursing team who helped in collecting the data for this audit report especially Mohammed Bashir, Ishraqa Mohammed, Sabir Sarfraz, the authors would like to thank Wesal Alalayet paharmacy resident student who helped in collecting the data for this audit report.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Lennard L. Therapeutic drug monitoring of antimetabolic cytotoxic drugs. Br J Clin Pharmacol 1999;47:131-43.  Back to cited text no. 1
National Comprehensive Cancer Network (NCCN). NCCN antiemesis guidelines emphasize 'delayed' emesis, new 5-HT3 inhibitors, and NK-1 blockers. J Support Oncol 2004;2:366.  Back to cited text no. 2
Natale JJ. Overview of the prevention and management of CINV. Am J Manag Care 2018;24:S391-7.  Back to cited text no. 3
Mansy W, Al-Salloum H, Alnahas TM, Khurshid F, Al-Omar HA. Effectiveness of antiemetics in the control of chemotherapy-induced nausea and vomiting in a tertiary care hospital in Saudi Arabia. Med Sci 2020;24:1103-10.  Back to cited text no. 4
Alsalloum HF. Evidence-Based Clinical Practice Guideline for Antiemetics Regimens for Chemotherapy Induced Nausea and Vomiting. Riyadh, 2016 ©King Saud University, 2016. King Fahd National Library Cataloging-in-Publication Data; 2016.  Back to cited text no. 5
Aseeri M, Mukhtar A, Al Khansa S, Elimam N, Jastaniah W. A retrospective review of antiemetic use for chemotherapy-induced nausea and vomiting in pediatric oncology patients at a tertiary care center. J Oncol Pharm Pract 2013;19:138-44.  Back to cited text no. 6
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Hesketh PJ. Comparative review of 5-HT3 receptor antagonists in the treatment of acute chemotherapy-induced nausea and vomiting. Cancer Invest 2000;18:163-73.  Back to cited text no. 9
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Amer YS, Wahabi HA, Abou Elkheir MM, Bawazeer GA, Iqbal SM, Titi MA, et al. Adapting evidence-based clinical practice guidelines at university teaching hospitals: A model for the Eastern Mediterranean Region. Journal of evaluation in clinical practice. 2019 Aug;25(4):550-60.  Back to cited text no. 13
Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2011;29:4189-Erratum in: J Clin Oncol 2014;32:2117.  Back to cited text no. 14
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Aapro M. CINV: Still troubling patients after all these years. Support Care Cancer 2018;26:5-9.  Back to cited text no. 17
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Roila F, Molassiotis A, Herrstedt J, Aapro M, Gralla RJ, Bruera E, et al. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol 2016;27:v119-33.  Back to cited text no. 19


  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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