Abstract
Introduction
Chemotherapy-induced nausea and vomiting (CINV) are problematic treatment-related adverse effects. 1 However, the use of clinical practice guideline (CPG)-consistent CINV prophylaxis has led to substantial improvements in CINV control.2–5 Current pediatric CPGs for prophylaxis of acute CINV in chemotherapy-naïve patients or those who have not experienced breakthrough or refractory chemotherapy-induced vomiting (CIV) (primary prophylaxis) recommend a serotonin receptor antagonist (5-HT3RA; e.g. ondansetron, granisetron or palonosetron) alone or in combination with other antiemetic agents.6–10 Palonosetron differs from ondansetron and granisetron in that it induces receptor internalization prolonging the inhibition of receptor function. 10 Compared to other 5-HT3RAs, palonosetron alone or in combination with dexamethasone may result in improved CINV control in patients receiving highly emetogenic chemotherapy (HEC).9,11,12 Further, palonosetron use during the acute phase is superior to ondansetron and granisetron in controlling vomiting during the delayed phase.9,12 5-HT3RAs do not appear to differ significantly in terms of safety. 13
SickKids’ CINV prevention and management policy was updated in 2017 using the most recent CPG at that time. 6 Due to the high cost of palonosetron, the SickKids’ policy limited its use to breakthrough CINV management in patients receiving HEC or hematopoietic stem cell transplant/cellular therapy (HSCT/CT) conditioning containing HEC or prophylaxis in patients with refractory CINV about to receive HEC (secondary prophylaxis). 14 The SickKids’ policy also included palonosetron dosing recommendations. Patients 12 years of age and older could receive either palonosetron orally or intravenously (IV). The palonosetron IV dose was capped at 1.5 mg for patients 17 years of age and older. CPG recommendations and the adapted SickKids’ policy statements are summarized in Supplemental Table S1.
This study was undertaken to determine the level of discordance between actual palonosetron use and our institutional CINV policy and the CPG from which the policy was adapted.
Methods
A retrospective review was conducted from 1 July 2019 to 30 June 2020 at SickKids, an academic, pediatric hospital in Toronto, Canada. The primary objective was to determine the discordance of palonosetron use with (a) the SickKids’ policy for CINV prevention and treatment (policy-discordant) and (b) the CPGs upon which our policy was based (CPG-discordant). The secondary objectives were to describe (a) characteristics of policy-discordant and CPG-discordant palonosetron use and (b) the extent of acute phase CIV control experienced by patients receiving palonosetron.
Patients
All oncology and HSCT/CT patients less than 18 years old who received at least one IV or oral palonosetron dose at SickKids during an inpatient admission or an ambulatory clinic visit during the indicated timeframe were included. Eligible patients were identified through a drug utilization report from the electronic health record. Patients who received palonosetron but were not under the care of the oncology service or were not undergoing HSCT/CT were excluded.
Data collected
Data collected from the health record were demographic information, chemotherapy regimen, CIV control history, details of palonosetron use, antiemetic regimen and the date and time of each vomit during the acute and delayed phases. Data were collected for each chemotherapy block (period of consecutive days of IV and/or intramuscular chemotherapy administration) that included palonosetron, starting at the beginning of the acute phase and continuing until the end of the delayed phase. The acute phase started with administration of the first chemotherapy dose of the chemotherapy block and ended 24 h following the last chemotherapy dose in the chemotherapy block.14,15 The delayed phase started at the end of the acute phase and continued for 96 h.14,15 Chemotherapy regimen emetogenicity was assigned using the pediatric chemotherapy emetogenicity classification CPG. 16 If the chemotherapy was not listed in this CPG, the American Society of Clinical Oncology, Multinational Association of Supportive Care in Cancer or National Comprehensive Cancer Network classifications were used sequentially as necessary.17–19
Analysis
Descriptive statistics were utilized to describe the characteristics of patients receiving palonosetron and reasons for its use.
Discordance with the institutional policy and the source CPG was determined by assessing whether the palonosetron indication and dose matched those indicated in Supplemental Table S1. Doses were considered policy- or CPG-discordant if they differed from the recommended doses by more than 10%. Policy- and CPG-discordant chemotherapy blocks were not mutually exclusive.
CIV control was reported as a proportion in the subset of chemotherapy blocks where palonosetron was given for CIV prophylaxis and for which information regarding vomiting episodes were available in the health record. Complete CIV control was defined as no emesis and no rescue medication use during the phase of interest. 16 Partial and failed CIV control were defined as 1–2 or 3 or more emetic episodes in 24 h during the phase of interest, respectively. 17
Results
One hundred thirty-six patients were screened for study inclusion based on a computer-generated report, 14 patients excluded, reasons for exclusion were no chemotherapy administered, no palonosetron administered, palonosetron dose administered outside the study period, concurrent total body irradiation and patient greater than 18 years (Figure S1).
Four hundred and thirty-eight chemotherapy blocks, representing 122 patients, receiving 595 palonosetron doses were included. Each patient contributed a median of 2 (range: 1 to 45) chemotherapy blocks. Characteristics of patients, chemotherapy blocks and palonosetron use are summarized in Table 1.
Characteristics of included patients, chemotherapy blocks during which palonosetron was administered and palonosetron dosing.
CPG, clinical practice guideline; HSCT/CT, Hematopoietic stem cell transplant/cellular therapy; HEC, highly emetogenic chemotherapy; MEC, moderately emetogenic chemotherapy; LEC, low emetogenic chemotherapy; MinEC, minimally emetogenic chemotherapy; CINV, chemotherapy-induced nausea and vomiting; IV, intravenously.
aAll chemotherapy blocks analyzed.
bReported at the first included chemotherapy block within the study period.
Reasons for discordant palonosetron use by number of chemotherapy blocks.
CPG, clinical practice guideline.
aNote that palonosetron use was policy-concordant or CPG-concordant during 124 and 326 chemotherapy blocks, respectively.
Palonosetron use was policy-discordant or CPG-discordant during 314 (72%) and 112 (26%) chemotherapy blocks, respectively (Table 2). The most common reason for policy-discordance was the use of palonosetron for primary CINV prophylaxis (57%; 178/314; see Table S1 for definitions). The most common reason for CPG discordance was prescription of a lower-than-recommended palonosetron dose (73%; 82/112).
Acute phase CIV control was evaluated in 295 chemotherapy blocks; data were insufficient to evaluate delayed phase CIV control. Complete CIV control during the acute phase was achieved in 66% (195/295) of chemotherapy blocks when palonosetron was administered for primary prophylaxis, refractory or breakthrough CIV, regardless of chemotherapy emetogenicity and concurrent antiemetics received. The antiemetic regimens prescribed and reported CIV control are summarized in Supplemental Table S2.
Discussion
During the study period, palonosetron use at our institution was largely discordant with institutional policy but concordant with the CPG recommendations.
The benefits of CPG-consistent care are well established. CPG-consistent care has improved patient outcomes in CINV prevention.2,3,20–22 Yet, in practice, the extent of CPG implementation tends to be low. 20 Variation in CPG uptake may be explained by organizational factors including prioritization of evidence-based care and the availability of resources to implement CPGs. 20 Institutions may balance these factors differently than clinicians and patients.
It is interesting that CPG-discordant palonosetron use was lower than policy-discordant use in our study. Adaptation of the 2017 CPG to create the SickKids’ policy incorporated an effort to contain palonosetron costs by restricting its use. It is to be expected that institutional resources would be heavily weighted in the adaptation of the source CPG recommendations. We speculate that many clinicians involved in antiemetic selection for patients were aware of the source CPG and the evidence underpinning its recommendations and applied this knowledge when making patient-specific decisions. After study completion, the SickKids’ policy was updated in 2022 to include palonosetron for primary prophylaxis in patients receiving HEC who are not able to receive dexamethasone and aprepitant. 23 This reflects the actual palonosetron use seen during our study period and aligns with the updated CINV CPG which strongly recommends the use of palonosetron over other 5HT3RAs for patients receiving HEC for whom either dexamethasone, fos(aprepitant) or both are not suitable. 9
Our study was limited due to its retrospective nature. Its strength was the consistent application of data element definitions.
Despite policy limitations on palonosetron use, it was commonly used for primary prophylaxis at our institution during the study period. With a recent policy update, future palonosetron use will likely align with both healthcare professional values and current CPG recommendations.
Supplemental Material
sj-docx-1-opp-10.1177_10781552241233489 - Supplemental material for Palonosetron in pediatric patients: A single-center, retrospective evaluation of policy and clinical practice guideline discordance
Supplemental material, sj-docx-1-opp-10.1177_10781552241233489 for Palonosetron in pediatric patients: A single-center, retrospective evaluation of policy and clinical practice guideline discordance by Meredith Ames, Priya Patel, L Lee Dupuis and Alicia Koo in Journal of Oncology Pharmacy Practice
Footnotes
Author statement
Data availability
Declaration of conflicting interests
Funding
ORCID iDs
Supplemental material
References
Supplementary Material
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