REVIEW For reprint orders, please contact: [email protected]

Comparative effectiveness research in antineoplastic-induced nausea and vomiting control in children Antineoplastic-induced nausea and vomiting (AINV) is one of the most distressing adverse effects experienced by adult and pediatric patients receiving antineoplastic agents. Despite this, evidence of the efficacy and safety of antiemetic interventions in children is limited, and prevention and treatment approaches vary widely between centers. The purpose of this review is: first, to describe the barriers to comparative antiemetic effectiveness research in AINV control in children; second, to highlight limitations of the currently available pediatric AINV evidence; third, to summarize and discuss comparative effectiveness research specific to AINV control in children, with a focus on agents recommended in evidence-based guidelines developed for acute phase AINV control; and finally, to offer guidance regarding future comparative effectiveness research in this field. KEYWORDS: antiemetics n antineoplastic-induced nausea and vomiting n chemotherapyinduced nausea and vomiting n comparative effectiveness research n guidelines n pediatrics

Jacqueline Flank*1 & L Lee Dupuis2 Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Department of Pharmacy, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada 2 Leslie Dan Faculty of Pharmacy, University of Toronto, Department of Pharmacy, Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada *Author for correspondence: Tel.: +1 416 813 7641 Fax: +1 416 813 5421 [email protected] 1

Antineoplastic-induced nausea and vomiting (AINV) is considered to be one of the most bothersome adverse effects experienced by both adults and children receiving antineoplastic treatment [1,2]. Although the availability of antiemetic agents, such as serotonin (5-HT3) receptor antagonists and corticosteroids has improved nausea and vomiting control, AINV continues to limit the quality of life of children receiving chemotherapy [3]. Lack of AINV control may also lead to associated clinical problems, such as nutritional deficits, dehydration, electrolyte abnormalities or esophageal tears [4,5]. Occasionally, patients may choose to terminate antineoplastic treatment prematurely due to uncontrolled AINV. The goal of achieving complete AINV control remains challenging since available pediatric evidence in this field is limited and, as a result, clinical practice varies between centers and between clinicians. It is essential to the provision of optimal supportive care that evidence for the prevention and treatment of AINV in children be synthesized and evidence-based guidelines be developed. Such guidelines align well with comparative effectiveness research (CER) since they encourage informed decision-making related to clinical care by clinicians and patients. Clinical practice guidelines also facilitate health system quality improvement and in this way support the goal of CER [6]. This paper will review barriers to comparative antiemetic effectiveness research in pediatric oncology, highlight limitations of the evidence currently available in this field, offer guidance for future research and summarize comparative studies involving the antiemetic agents currently recommended for acute AINV control in children receiving highly (HEC) and moderately (MEC) emetogenic antineoplastic therapy: 5-HT3 receptor antagonists, corticosteroids and aprepitant. Barriers to comparative antiemetic effectiveness research in AINV control in children

The incorporation of methodological standards in studies related to CER ensures that the results are meaningful, unbiased and relevant [7]. One of the biggest limitations

10.2217/CER.13.93 © 2014 Future Medicine Ltd

3(2), 185–196 (2014)

part of

ISSN 2042-6305

185

review  

Flank & Dupuis

to the ability to synthesize evidence and compare antiemetic interventions in pediatric oncology is the considerable variation in AINV risk assessment, end point definitions, study outcomes and outcome measurements used. Some of this variation is discussed below. ■■ Patient-related limitations AINV risk & emetogenicity classification

The risk of a child experiencing AINV is primarily determined by the emetogenic potential of the chemotherapy they will be receiving [8]. The Pediatric Oncology Group of Ontario (POGO) recently published a guideline outlining the acute emetogenic potential of antineoplastic medication in pediatric cancer patients [9,10]. Prior to this guideline, the classification of antineoplastic agents as having minimal, low, moderate or high emetogenic risk in pediatric patients was challenging and was most often assessed using guidelines developed for adult cancer patients. Table 1 summarizes these definitions and provides examples of antineoplastic agents within each category. The available pediatric evidence to support the recommendations of this guideline is limited. In fact, pediatric data are available to support the classification of only 14 of the 101 antineoplastic agents included in the guideline. Use of a uniform, well-substantiated approach to the classification of antineoplastic emetogenicity in pediatric studies of antiemetic interventions would be ideal.

Genetics of AINV & drug response

There is a growing appreciation that genetic factors often contribute to individual variability in susceptibility to AINV and to drug response. More specifically, genetic variations in drug-metabolizing enzymes and drug transport systems may lead to large differences in drug concentrations, which may in turn lead to toxicity or ineffective drug treatment in individual patients. This variability may explain, at least partially, why antiemetic efficacy remains suboptimal in some patients. For example, polymorphisms in the cytochrome P450 CYP2D6 enzyme, which is involved in the metabolism of ondansetron, predispose some patients to ondansetron failure [11]. An individual’s genetic make-up may also make them more inherently susceptible to experience AINV. For example, female gender has been identified as a risk factor for experiencing AINV in adult cancer patients [12,13]. Investigators are also beginning to appreciate the possibility that individuals of different ethnicities may be more or less likely to experience AINV [12,14]. Ideally, trials evaluating antiemetic interventions would incorporate genetic analysis into the design and stratify randomization to balance treatment arms. Although difficult in pediatrics, large randomized controlled trials would allow for even distribution of patients with variable genetic make-up among different treatment arms. Trials using ondansetron in the comparator arm that do not assess CYP2D6

Table 1. Emetogenicity definitions and examples of antineoplastic agents within each category. Emetogenicity ranking

Definition

Examples of antineoplastic agents in this class (noninclusive)

Minimal

Less than 10% frequency of emesis in the absence of effective prophylaxis

Asparaginase Oral mercaptopurine Vincristine

Low

10 to less than 30% frequency of emesis in the absence of effective prophylaxis

Etoposide Oral busulfan† Topotecan

Moderate

30 to less than 90% frequency of emesis in the absence of effective prophylaxis

Daunorubicin† Doxorubicin† Ifosfamide

High

Greater than 90% frequency of emesis in the absence of effective prophylaxis

Carboplatin† Cisplatin† Methotrexate ≥12 g/m2†

Supported by pediatric-specific evidence. Data taken from [9,10]. †

186

J. Comp. Eff. Res. (2014) 3(2)

future science group

Comparative effectiveness research in antineoplastic-induced nausea & vomiting control in children 

polymorphisms a priori must acknowledge genetic variability as a potential study limitation. ■■ Limitations related to end point definitions & measurement Type of AINV

It is well understood that patients may experience AINV at several different time points relative to antineoplastic administration. Table 2 outlines generally accepted definitions for acute, delayed, anticipatory and breakthrough AINV [15–17]. Alternate terms and definitions are, however, commonly reported in individual studies. For example, Sepulveda-Vildosa et al. defined the acute phase of AINV as the “first 3 days of treatment and the delayed phase as the following 4–7 days” in their study comparing palonosetron versus ondansetron in children [18]. Since the authors of this study did not specify the duration of the antineoplastic therapy that children received, it is challenging to interpret their findings with respect to complete AINV control during a specific phase. Similarly, reports of anticipatory nausea and vomiting have been described as nausea, vomiting or retching occurring ‘before the start of a new cycle of chemotherapy’ or ‘shortly before the initiation of treatment’ with no definitive timeframe specified [19,20]. Different prevention and treatment approaches are probably required depending on the type of AINV a patient is at risk of experiencing. Therefore, it is essential to appropriately define the different phases of AINV for the purposes of effective comparative research. Emetic episodes

Most pediatric studies of AINV control focus on emetic episodes as a primary end point.

review

Problems with interpretation and comparison of study results may arise if what is considered to be an emetic episode is not clearly defined. For example, the definition may consist of vomiting only or both vomiting and retching [21,22]. If retching is not included in a study’s definition of an emetic episode, the total number of emetic episodes experienced by a patient may be under-reported. Outcome measures

Complete AINV control is often reported as the primary outcome measure in many studies of antiemetic interventions in both pediatric and adult patients. However, definitions of complete AINV control range from simply the use of no breakthrough antiemetic agents during a defined period to a much more comprehensive definition including no emetic episodes plus a predetermined nausea severity ranking using a validated tool plus use of no breakthrough antiemetic agents [15,17]. Nausea is increasingly recognized in adult cancer patients as a more significant determinant of quality of life than vomiting and recent adult antiemetic studies have included nausea assessment as a secondary end point with the primary end point of complete control defined as no vomiting, no retching, no rescue therapy and no discontinuation from the study [23–25]. Optimal AINV control in pediatric patients was recently defined as no vomiting, no retching, no nausea, no use of antiemetic agents other than those given for AINV prevention and no nausea-related change in the child’s usual appetite and diet [15,17]. This comprehensive definition can be used as a model for studies wishing to evaluate complete control of AINV as it includes all of the components related to a patients’ AINV experience.

Table 2. Phases of antineoplastic-induced nausea and vomiting. Phase of AINV

Definition

Acute

Nausea, vomiting and/or retching that occurs within 24 h following the administration of antineoplastic therapy

Delayed

Nausea, vomiting and/or retching that occurs more than 24 h after and usually within 7 days of administration of antineoplastic therapy

Anticipatory

Nausea, vomiting and/or retching that occurs within 24 h prior to administration of antineoplastic therapy

Breakthrough

Nausea, vomiting and/or retching that occurs during any phase despite adequate antiemetic prophylaxis with the usual standard of care

AINV: Antineoplastic-induced nausea and vomiting. Data taken from [14,15,17].

future science group

www.futuremedicine.com

187

review  

Flank & Dupuis

Inclusion of nausea severity in the primary outcome measure is ideal as this measure then truly reflects control of AINV. It may also be worthwhile to report both control of AINV and antineoplastic-induced nausea (AIN) and antineoplastic-induced vomiting (AIV) as distinct end points since there is an emerging appreciation that patients may experience nausea without vomiting and different interventions may be required for AIN and AIV [15–17,26]. For an appropriate understanding of study results, authors should report the proportion of patients who experience complete AINV control, using an explicitly stated and comprehensive definition.

cancer patients. Limitations in the current literature addressing AINV control in children receiving antineoplastic therapy include patient-related factors, variability in study definitions and variability in outcomes and outcome measures. The next section of this article summarizes available CER in this domain. Unfortunately the evidence available to date has not surmounted the methodological barriers described above. A standardized methodological approach for future AINV studies will allow comparison of the available evidence. This may aid synthesis of this information and the development of more robust clinical practice guidelines.

Nausea assessment

Available comparative pediatric acute phase AINV research

Supportive care for pediatric cancer patients is best guided by patient-reported outcomes related to symptom assessment as it has been shown that reliable and valid patient-reported outcomes can contribute to improvements in clinical care and decision-making related to treatment [27]. Patient-reported outcomes of subjective symptoms, such as nausea, can be particularly challenging in children. As a result, investigators often exclude nausea severity as a study end point owing to challenges related to its measurement. Other investigators have either inadequately described the methods used for nausea assessment in children or have used nonvalidated child-report tools. Parents and caregivers may underestimate a child’s nausea [28]. It is, therefore, imperative that validated pediatric tools be used for the reporting of nausea severity experienced by children. By contrast, the number of emetic episodes that a patient experiences can be easily measured objectively either by direct observation or by patient self-report [29]. In recognition of the need to obtain nausea severity assessments from the child, several pediatric nausea severity assessment instruments have now been developed [28–31]. The Pediatric Nausea Assessment Tool has been developed and validated in pediatric cancer patients 4–18 years of age and has been used successfully in multiple observational studies for patient self-reporting of nausea severity [28,32,33]. The use of validated tools, such as the Pediatric Nausea Assessment Tool, for the assessment of nausea severity is essential for the success of future trials of antiemetic interventions in children receiving antineoplastic medication. Overall, there are many barriers to effective CER specific to AINV control in pediatric

188

J. Comp. Eff. Res. (2014) 3(2)

There are very few examples of CER specific to AINV control in pediatric oncology. Much of the currently available literature consists of retrospective studies, case reports, observational studies and prospective, unblinded studies with enrollment of a small number of patients. There are very few randomized controlled pediatric trials related to AINV. The guideline for the prevention of acute AINV in pediatric cancer patients developed by POGO and the Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology antiemetic guideline in children receiving chemotherapy are recent examples of the synthesis of available evidence related to this topic [15,17,34]. Since its publication, the POGO guideline has been endorsed by the Multinational Association of Supportive Care in Cancer. The POGO guideline summarizes pharmacological and nonpharmacological interventions that, based on the best available evidence and expert consensus, will provide optimal control of acute AINV in most patients. Specific recommendations vary depending on the emetogenicity ranking of the antineoplastic therapy patients are scheduled to receive. In general, a first-generation 5-HT3 receptor antagonist (ondansetron or granisetron) plus dexamethasone are recommended for all children receiving MEC or HEC. The addition of aprepitant is recommended for children greater than 12-year-olds who are receiving HEC that is not known or suspected to interact with aprepitant. The recommendation for the use of aprepitant in these patients is based on limited evidence related to its use in adolescent patients [35–37]. These ­antiemetic agents will be the focus of this review.

future science group

Comparative effectiveness research in antineoplastic-induced nausea & vomiting control in children 

The POGO acute AINV prevention guideline was used as a foundation for this review of comparative effectiveness and this review may be considered a companion to the POGO guideline as it highlights limitations of the currently available evidence and barriers to comparative research in this field. The literature search initially conducted for development of the POGO guideline was updated in August 2013. Electronic databases searched include Medline, Embase, Cochrane Central Register of Controlled Trials (CCRCT), Allied and Complementary Medicine (AMED), Health Technology Assessment (HTA), NHS Economic Evaluation Database (NHSEED) and the Cumulative Index to Nursing and Allied Health Literature database. The complete search strategy including search terms and limits used can be found in Appendix C of the POGO guideline [15,17]. The same inclusion criteria were applied to the selection of evidence to be included in this review as had been applied to the POGO guideline with two exceptions: included studies were limited to those which were comparative in nature and those which evaluated a 5-HT3 antagonist, dexamethasone or aprepitant. Specifically, studies were included if: they were published in full text (i.e., abstracts were excluded); they were published in English or French; they reported pediatric data separately; it was possible to determine the emetogenicity of the antineoplastic therapy administered using the POGO classification guideline or an assessment provided by the study’s author(s); they provided an explicit or implicit definition of complete acute AINV response; and they reported the complete acute AINV response rate as a proportion or percentage [15,17]. Studies that focused on the selection of a 5-HT3 receptor antagonist, the benefit of the addition of a corticosteroid to a 5-HT3 receptor antagonist, and whether or not different dosage forms or routes of administration impact efficacy of antiemetic agents were highlighted for the purpose of this review. Figure 1 depicts the results of the updated literature search, which yielded a total of 69 new articles published since November 2011 (the cutoff date for the original POGO literature search). Unfortunately, very little literature has been published in this field in the past 2 years and none of the studies identified by the updated literature search met inclusion criteria. Evidence summary tables initially developed for the POGO guideline were adapted to include comparative studies

future science group

review

in the categories described above (Tables 3–5). Only one comparative study involving the use of aprepitant in adolescents was identified during the initial POGO literature search [37]. This study was not included in this review as only six adolescents participated and the results for these patients were not published separately from adult data. Details of the c­ omparative s­tudies included can be found below. ■■ Selection of 5-HT3 receptor antagonists

Examples of individual agents from this antiemetic class include ondansetron, granisetron, tropisetron and the newer second-generation 5-HT3 receptor antagonist, palonosetron. A meta-analysis of eight studies that evaluated the efficacy of 5-HT3 antagonists alone in the setting of HEC observed a complete AINV control rate of 66% (95% CI: 60–72) [15,17]. No studies comparing the effectiveness of 5-HT3 antagonists in children receiving antineoplastic therapy that met the criteria for inclusion in this review and that had not been incorporated into the POGO acute AINV guideline were identified. A summary of the available comparative evidence of agents in this class can be found in Table 3. Aksoylar et al. conducted a prospective, randomized comparison of granisetron (40 µg/ kg/day) versus tropisetron (0.2 mg/kg/day) in 51 children aged 1–17 years over 133 chemotherapy cycles, including 49 HEC treatment blocks [21]. Acute AIV and AIN control were assessed on the first day of treatment although the duration of antineoplastic therapy that patients received ranged from 1 to 8 days. Complete AINV control was defined as no vomiting and no nausea; retching was not included in the definition of an emetic episode. Episodes of nausea and vomiting were recorded daily by the same physician, the patient or a parent. As previously discussed, proxy-reported nausea severity assessment and omission of retching in the definition of an emetic episode may lead to under-reporting. Complete acute AINV control was achieved in 30% of HEC treatment blocks in the tropisetron group versus 32% in the granisetron group. No difference in tolerability of the two antiemetic agents was reported. Jaing et al. conducted a prospective study comparing the efficacy of a single dose of oral granisetron (0.5 mg administered to patients 25–50 kg, 1 mg administered to patients greater than 50 kg) versus intravenous (iv.) or oral ondansetron (0.15 mg/kg/dose for two doses 8 h

www.futuremedicine.com

189

review  

Flank & Dupuis

7 electronic databases searched

71 new citations identified 1 duplicate plus the POGO source guideline removed

69 titles and abstracts screened

64 excluded

■■ Addition of corticosteroids to 5-HT3 receptor antagonists

5 full-text articles screened

5 excluded: – 3 noncomparative studies – 1 study evaluating alternative antiemetic agent – 1 study where emetogenicity assessment not possible

0 studies included

Figure 1. Updated literature search flowchart. POGO: Pediatric Oncology Group of Ontario.

apart, followed by another dose orally 8 h later) in 33 children receiving MEC [38]. The acute phase was defined as the 24 h following administration of antineoplastic therapy and complete AINV control was defined as no vomiting and no need for rescue antiemetic medication. Nausea severity was to be reported by parents as a secondary end point. Complete AIV control was achieved by 61% of patients in the granisetron group and 45.5% of patients in the ondansetron group (p = 0.227). Although the authors initially intended to assess nausea severity, frequency and severity of nausea were not analyzed since only two episodes of nausea were reported during the study. Since no significant difference was observed in complete AIV control between the two treatment arms, the authors concluded that the choice between oral granisetron and iv. or oral ondansetron may be based on cost and ease of administration. In general, owing to the lack of evidence to suggest superior efficacy of any of the currently

190

available first-generation 5-HT3 receptor antagonists in pediatric patients, and the recommendation that these agents are equivalent in adult cancer patients, selection between ondansetron and granisetron for a patient receiving antineoplastic therapy can be based on practical aspects such as cost and available dosage forms [16,39]. Until more pediatric evidence regarding the use of palonosetron is available, this agent should probably be reserved for situations where unknown risks are likely outweighed by potential benefits. One such situation may be the adolescent patient who has previously failed guideline-consistent antiemetic prophylaxis [18,40–42].

J. Comp. Eff. Res. (2014) 3(2)

Although there is extensive clinical experience regarding the use of corticosteroids for the prevention of AINV in pediatric patients, very little comparative pediatric literature is available. Older studies have shown that corticosteroids are more effective than metoclopramide or chlorpromazine [43,44], but there are few evaluations of dexamethasone in combination with newer antiemetic agents. The use of a corticosteroid with a 5-HT3 receptor antagonist is considered the standard of care for patients receiving MEC or HEC as it has been shown that this combination results in improved acute AINV control compared with the use of a 5-HT3 receptor antagonist alone [15,17,45]. A meta-analysis of four studies evaluating the efficacy of a 5-HT3 antagonist plus dexamethasone in children receiving HEC observed a complete AINV control rate of 50% (95% CI: 43–57) [15,17]. This result may lead to the conclusion that administration of dexamethasone in conjunction with a 5-HT3 antagonist leads to inferior AINV control than the use of a 5-HT3 antagonist alone. However, the studies included in this meta-ana­lysis evaluated widely variable corticosteroid doses in small numbers of children and generally were of low quality. As will be discussed, the results of randomized controlled trials in children and a meta-ana­lysis conducted by Phillips et al. support the use of both a 5-HT3 antagonist and dexamethasone to optimize AINV control in children receiving HEC [45]. Specifically, Phillips et al. concluded that the addition of a corticosteroid to a 5-HT3 antagonist resulted in a relative risk of complete control of vomiting of 2.03 (95% CI: 1.35–3.04).

future science group

Comparative effectiveness research in antineoplastic-induced nausea & vomiting control in children 

review

Table 3. Comparative pediatric evidence related to the selection of a serontonin 3 receptor antagonist. Study (year)

Antiemetic agents evaluated

Study design

Patients (n)

Age range (years)

Chemo- Method naive of nausea patients assessment (n)

Response definition and results

Ref.

13

Unvalidated scale

Complete control defined as: no vomiting and no nausea Complete control: tropisetron: 30% (8 out of 27); granisetron: 32% (7 out of 22; no p-value reported)

[21]

Not stated

Unvalidated scale

Complete control defined as: no vomiting and no need for rescue medication Complete control: granisetron: 61% (20 out of 33); ondansetron: 45.5% (15 out of 33; p = 0.227)

[38]

Highly emetogenic antineoplastic therapy Aksoylar Tropisetron vs Prospective, et al. granisetron randomized (2001)

51 (133 1–17 antineoplastic blocks; 49 very highly emetogenic antineoplastic blocks)

Moderately emetogenic antineoplastic therapy Jaing et al. (2004)

Granisetron vs ondansetron

Randomized, 33 (66 open-label, antineoplastic crossover blocks)

3–18

Emetogenicity classification was either evaluated as per the Pediatric Oncology Group of Ontario guideline for classification of the acute emetogenic potential of antineoplastic medication in pediatric cancer patients or as designated by the study investigators [9,10].

Three studies evaluating the impact of the addition of a corticosteroid to a 5-HT3 receptor antagonist were included in the evidence base of the POGO guideline [22,46,47]. All three of these studies found that control of AINV improved in children when a corticosteroid, either dexamethasone or methylprednisolone, was given together with one of ondansetron, granisetron or tropisetron compared with the 5-HT3 antagonist alone. No new studies that met the criteria for inclusion in this review were identified in the updated literature search. Table 4 summarizes the available comparative pediatric evidence related to AINV control in children receiving a corticosteroid plus a 5-HT3 receptor antagonist. Alvarez et al. conducted a double-blind, placebo-controlled, randomized crossover comparison of iv. ondansetron (0.15 mg/kg × three doses) plus placebo versus iv. ondansetron (0.15 mg/kg × three doses) plus iv. dexamethasone (8 mg/ m 2 30 min prior to chemotherapy followed by 16 mg/m2 in divided doses) in 25 children aged 3–18 years receiving HEC over a range of 1–5 days [22]. The acute phase was not explicitly defined and the details regarding the duration of evaluation were not reported; however, investigators stated that antiemetic responses were reported while patients received the study drug. Complete AIV control was defined as no vomiting and no retching. Patients or parents and

future science group

nurses also graded nausea, appetite and general wellbeing on a daily questionnaire and on the nurses’ 12-h shift diary, respectively. Complete AIV control was observed in 23% of patients in the ondansetron plus placebo group versus 61% of patients in the ondansetron plus dexamethasone group. Although nausea was not assessed by patient report or using a validated tool and not reported as a primary outcome, minimal to no nausea was reported for 74% of patients receiving ondansetron plus dexamethasone compared with 52% of patients receiving ondansetron plus placebo. The results of this study support the addition of a corticosteroid to a 5-HT3 antagonist for optimal AINV control in pediatric patients receiving HEC. Ozkan et al. conducted a prospective observational study evaluating iv. tropisetron (0.2 mg/ kg to 5 mg maximum daily) with or without iv. dexamethasone (20 mg/m2 1 h prior to administration of cisplatin on day 1) in 15 children aged 0.5–15 years receiving cisplatin-based HEC [46]. An unvalidated grading scale based on a combined measure of nausea and vomiting was used to assess the efficacy of tropisetron. Again, the acute phase was not explicitly defined; however, response was assessed per 24 h period on the days that patients received chemotherapy. Complete AINV control was defined as no nausea and no vomiting. Complete control was observed in 50% of patients in the tropisetron

www.futuremedicine.com

191

review  

Flank & Dupuis

Table 4. Comparative pediatric evidence related to addition of a corticosteroid to a serotonin 3 receptor antagonist. Study (year)

Antiemetic agents evaluated

Study design

Patients (n)

Age Chemo- Method range naive of nausea (years) patients assessment (n)

Response definition and results

Ref.

3–18

Unvalidated scale

Complete control defined as: no vomiting or retching Complete control: ondansetron plus placebo: 23% (7 out of 30); ondansetron plus dexamethasone: 61% (17 out of 28; no p-value reported)

[22]

Unvalidated scale

Complete control defined as: no nausea and no vomiting Complete control: tropisetron alone: 50% (10 out of 20); tropisetron plus dexamethasone: 65% (13 out of 20; no p-value reported)

[46]

Unvalidated scale

Complete control defined as: no vomiting, nausea, loss of appetite or stomach discomfort Complete control: granisetron alone: 85% (18 out of 20); granisetron plus methylprednisolone: 95% (19 out of 20; no p-value reported)

[47]

Highly emetogenic antineoplastic therapy Alvarez et al. (1995)

Ondansetron plus placebo vs ondansetron plus dexamethasone

Double blind, 25 placebo controlled, randomized crossover

Özkan et al. (1999)

Tropisetron ± dexamethasone

Prospective, observational

16

15 (100 patients 0.5–15 Not in total over 350 stated antineoplastic blocks 15 patients received cisplatin during 40 antineoplastic blocks)

Moderately emetogenic antineoplastic therapy Hirota et al. (1993)

Granisetron vs Randomized granisetron plus controlled, methylprednicrossover solone

10 (20 antineoplastic blocks; 12 highly emetogenic; six moderately emetogenic and two blocks of low emetogenicity)

4–18

Not stated

Emetogenicity classification was either evaluated as per the Pediatric Oncology Group of Ontario guideline for classification of the acute emetogenic potential of antineoplastic medication in pediatric cancer patients or as designated by the study investigators [9,10].

group and by 65% of patients in the tropisetron plus dexamethasone group. The authors also compared the mean daily number of vomiting episodes between the two groups and found that patients who received dexamethasone in addition to tropisetron experienced significantly fewer vomiting episodes. On day 1 of treatment, patients in the tropisetron plus dexamethasone group experienced an average of 0.60 ± 1.35 emetic episodes, while mean emetic episodes experienced by patients in the tropisetron only group was 1.95 ± 2.16 (p 

Comparative effectiveness research in antineoplastic-induced nausea and vomiting control in children.

Antineoplastic-induced nausea and vomiting (AINV) is one of the most distressing adverse effects experienced by adult and pediatric patients receiving...
842KB Sizes 2 Downloads 3 Views