XML Template (2015) [20.3.2015–2:38pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/OPPJ/Vol00000/150015/APPFile/SG-OPPJ150015.3d
(OPP)
[1–9] [INVALID Stage]
Original Article
‘Acceptability’ of a new oral suspension formulation of mercaptopurine in children with acute lymphoblastic leukaemia
J Oncol Pharm Practice 0(0) 1–9 ! Nova Laboratories Ltd 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1078155215577808 opp.sagepub.com
Hussain Mulla1,2, Helen Buck3, Lisa Price4, Annie Parry4, Geoff Bell4 and Roderick Skinner5
Abstract Aim: The aim of this questionnaire-based survey was to determine the ‘acceptability’ of XaluprineÕ , a new oral liquid formulation of mercaptopurine, when administered chronically to children during the maintenance treatment phase of acute lymphoblastic leukaemia. Patients and methods: This was a single centre survey of children (aged 3 to 16 years) and their parents at a routine follow-up visit during the maintenance phase of acute lymphoblastic leukaemica treatment. The questionnaire probed for their views on overall acceptability such as taste, smell, incidences of vomiting, ease and willingness to take XaluprineÕ on a daily basis, and utilised a 5-point facial hedonic scale (1 ¼ bad, 5 ¼ good) as well as open/closed questions. Results: Twenty-two children were recruited; 17 (77%) scored taste between 3 and 5 (‘okay’ to ‘good’) and 20 (91%) scored smell between 3 and 5. Only four children (18%) reported an aftertaste. Of the five children (23%) who scored taste as 1 or 2 (‘bad’), three found taking all oral medicines difficult. Six children (27%) reported vomiting, but this was not considered related to XaluprineÕ . Seven children (32%) sometimes complained that they did not want to take XaluprineÕ ; 15 (68%) never complained. In response to the question, ‘How easy is it for you to take XaluprineÕ ?’ 18 children (82%) reported that it was ‘Easy all the time.’ This was more favourable than other oral liquid medicines that they were taking concurrently. Conclusion: The results of this survey show that XaluprineÕ has good overall acceptability in the paediatric population and suggests that XaluprineÕ is an important, alternative, age-appropriate formulation of mercaptopurine.
Keywords Mercaptopurine, palatability, acceptability, acute lymphoblastic leukaemia
Introduction Mercaptopurine is a cornerstone of all maintenance therapy drug regimens for acute lymphoblastic leukaemia (ALL). The efficacy of mercaptopurine for keeping children and adolescents with ALL disease free has been established by a number of national and international trials.1 However, until recently the only approved formulation of mercaptopurine has been a single 50 mg tablet; less than 10% of children with ALL are prescribed doses that match this tablet configuration.2 Moreover, the lack of an age-appropriate mercaptopurine formulation has been an obstacle in treating children, especially young children who are unable to take solid dosage forms.3 XaluprineÕ
1
Nova Laboratories Limited, Leicester, UK Department of Pharmacy, University Hospitals of Leicester, Leicester, UK 3 St Albans, Herts, UK 4 Sir James Spence Institute, Great North Children’s Hospital, Royal Victoria Infirmary, Newcastle UK 5 Department of Paediatric and Adolescent Haematology and Oncology and Children’s BMT Unit, Great North Children’s Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, UK 2
Corresponding author: Hussain Mulla, Department of Pharmacy, Glenfield Hospital, University Hospitals of Leicester, Groby Road, Leicester, LE3 9QP, UK. Email: [email protected]
Downloaded from opp.sagepub.com at UNIVERSITE DE MONTREAL on June 12, 2015
XML Template (2015) [20.3.2015–2:38pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/OPPJ/Vol00000/150015/APPFile/SG-OPPJ150015.3d
(OPP)
[1–9] [INVALID Stage]
2
Journal of Oncology Pharmacy Practice 0(0)
(PurixanÕ in the US) is a newly approved raspberryflavoured oral suspension formulation of mercaptopurine, and offers children, parents and healthcare professionals an alternative to the tablet. For young children in particular, XaluprineÕ is potentially a significant improvement over the existing tablet presentation and addresses compliance issues such as accuracy, flexibility and individualisation of dosing, as well as palatability and acceptability. The palatability of medications (smell, taste, aftertaste and mouth feel), in particular that of liquid formulations used in young children is an important consideration and is believed to play a major role in adherence with drug therapy in paediatrics. Better tasting formulations also make it easier for parents to administer much needed medication.4 The unpleasant taste of antibiotic and antiretrovirals has been widely cited as a common reason for non-adherence, while a number of questionnaire-based studies of compliance with antibiotic treatments in children have reported a correlation between taste and adherence rates.5 The ramifications of poor adherence, namely treatment failure with associated complications, re-treatment, overtreatment and emerging resistance as well as financial costs, are serious healthcare concerns. Specifically in the treatment of children with ALL, mercaptopurine adherence rates below 90% are associated with increased risk of disease relapse (hazard ratio, 3.1, p ¼ 0.04). Moreover, 31% of relapses have been attributed to non-adherence.6,7 Both European and US regulators have specified the need to assess the ‘acceptability’ of paediatric medicinal products as an integral part of pharmaceutical development studies. However, assessment of the acceptability of a dosage form for children is not limited to palatability alone.8 Acceptability is defined as the overall ability of the patient and caregiver (the ‘user’) to use a medicinal product as intended and is determined by both the characteristics of the user (age, ability, disease type and state) and the medicinal product.8 For an oral liquid medicine, this might include: need for modification prior to administration (e.g. reconstitution), palatability, appearance, physical burden of dose (dosing volume), dosing regimen, ease of use of administration device and the primary and secondary container closure system. Moreover, simple taste preference studies involve only a single dose of the test formulation and it is possible that taste perception may change with prolonged administration. It is also unclear whether the results of these single dose studies are predictive of overall acceptability during periods of continuous use.9 Indeed, it is this overall acceptability of a medicine that is perhaps even more critical for a chronically administered medicinal product, such as mercaptopurine, compared to a medicine intended as a short-course,
such as an antibiotic. It is under the conditions of chronic administration that both child and carer need to be sufficiently at ease with the product to ensure high levels of adherence. Studies to assess the acceptability of medicinal products intended for chronic administration should ideally be conducted in the target disease and patient population. The perception of taste of medicines has been shown to be different between adults and children, between healthy and sick children and following exposure to chemotherapy.10,11 From an ethical perspective, it would not be appropriate to conduct acceptability testing of mercaptopurine in healthy volunteer children because of the lack of any benefit to the participant as well as the risk of adverse effects from the medication. Hence, the aim of this questionnaire-based survey of XaluprineÕ was to assess the ‘user’ acceptability during chronic administration in children with ALL, who form the target patient population for this medication.
Patients and methods This study was designed as a non-interventional, paperbased, face-to-face survey of children and their parents during the interim maintenance and maintenance phases of ALL treatment and was conducted at the Great North Children’s Hospital, Newcastle, UK. The survey protocol, questionnaire and consent forms were approved by a local ethics committee and the hospital research and development department. The survey was performed in accordance with the Declaration of Helsinki. Children aged 3 to 12 years with a diagnosis of ALL were eligible. Patients were excluded where children and their parents were both non-English speaking, where children were non-verbal or where the child’s developmental status prevented them from using the survey scales. The centre followed their normal ALL treatment protocols for the prescribing of mercaptopurine therapy as part of combination chemotherapy. The choice between mercaptopurine administration as tablets or XaluprineÕ was based on two criteria: clinician preference (for example, the desire to achieve an accurate dose) and patient/parent preference of dosage form. The survey of XaluprineÕ only recruited those children who had taken the oral liquid for a minimum of four weeks. The number of subjects who were initiated on XaluprineÕ and switched to tablets prior to enrolment was recorded. The questionnaire consisted of three types of questions: open questions, closed questions with categorical responses (e.g. yes/no or choose one of the following), and questions relating to the taste and smell using a 5-point facial hedonic scale. This scale, which allows for indication of preferences by pointing at a pictorial
Downloaded from opp.sagepub.com at UNIVERSITE DE MONTREAL on June 12, 2015
XML Template (2015) [20.3.2015–2:38pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/OPPJ/Vol00000/150015/APPFile/SG-OPPJ150015.3d
(OPP)
[1–9] [INVALID Stage]
Mulla et al.
3
scale of facial expressions, has been commonly employed in palatability studies12,13 (Figure 1). Compared to spontaneous verbal judgment, this method has the advantage of being a more standardised procedure. Studies have shown that children as young as four years can understand and use up to 7-point hedonic scales to indicate whether a substance is pleasing to their taste.9 Since it is routine practice to monitor blood counts regularly during maintenance treatment (typically every 1–2 weeks), the researchers obtained written informed consent of children and their parents (and assent from younger children if appropriate) at one of these visits after the investigator had discussed the survey with the parent and child and provided them the opportunity to read written information about the survey. After consent, a research nurse accompanied each child and parent/carer to a private test area where the study procedures and rating scale were described. The survey sought the views of both parent and child where possible. In the case of very young children where this was not possible, only the parent was surveyed. In each case, the research nurse conducted the survey and recorded the verbal responses to the open and closed questions and where facial hedonic scales were utilised, the parent/ child was asked to indicate their preference by putting their mark on the pictorial scale of facial expressions.
Statistical analysis All data collected were double entered into an Excel database. Demographic data and responses to all
Bad
OK
Good
Figure 1. Visual analogue scale incorporating 5-point facial hedonic scale.
questions were summarised by age group and overall. Categorical data were presented using counts and percentages and continuous variables presented using the mean, standard deviation (SD), median, minimum, maximum and number of subjects (N). All analysis was undertaken using SAS (v.9.1.3).
Results During the period July 2013 to June 2014, a total of 22 patients were enrolled and surveyed: 12 males and 10 females. Of the 22 subjects recruited, 16 subjects were below the age of six (minimum 3.2 years) and six subjects were above the age of six (maximum 10.2 years) (Table 1). In seven subjects (44%) below the age of six years, the survey was completed by seeking the view of parent only; for children >6 years, this only occurred on one (16%) occasion. On all other occasions, the survey was completed by seeking the views of both parent and child together. Since the survey began during the interim period between cessation of UKALL2003 and initiation of UKALL 2011, children recruited into the survey were being treated according to one of three active protocols; UKALL 2003, ALL interim guidelines 2011 and UKALL 2011. Although in some cases XaluprineÕ had been initiated during the interim maintenance phase, all children at the time of the survey were in the maintenance phase of therapy (Table 2). All children had received at least four weeks of XaluprineÕ therapy and the median period of continuous use was 11 weeks. XaluprineÕ is formulated as a 20 mg/ml oral suspension and the dosing volume ranged between 0.5 and 3.5 ml. In all but one child for whom a spoon was used, dosing was achieved using an oral syringe; almost all (95%) of subjects found it ‘very easy’ to use the oral syringe (Table 2). Seventeen out of 22 (77%) subjects scored taste between 3 and 5 (‘okay’ to ‘good’); 20 out of 22 (91%) subjects scored the smell between 3 and 5 (Figure 2). Only four (18%) subjects reported an aftertaste. Of the five subjects who scored taste as 1 or 2
Table 1. Demography.
Age (years) Sex Protocol week of ALL treatmenta Period of continuous XaluprineÕ use at the time of survey XaluprineÕ dose volume (ml)
3 to < 6 years (n ¼ 16)
6 to < 16 years (n ¼ 6)
All patients (n ¼ 22)
4.0 (3.2–5.8) 7 F; 9 M 61 (33–130) 9 (2–38)
7.2 (6.2–10.2) 3 F; 3 M 74 (42–118) 24.5 (3.0–56.0)
5.2 (3.2–10.2) 10 F; 10 M 65 (33–130) 11.0 (2.0–56.0)
2.5 (0.5–3.5)
1.75 (0.9–3.5)
2.5 (0.5–3.5)
a
All subjects were in the maintenance phase; results are presented as median (range).
Downloaded from opp.sagepub.com at UNIVERSITE DE MONTREAL on June 12, 2015
XML Template (2015) [20.3.2015–2:38pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/OPPJ/Vol00000/150015/APPFile/SG-OPPJ150015.3d
(OPP)
[1–9] [INVALID Stage]
4
Journal of Oncology Pharmacy Practice 0(0)
Table 2. Maintenance therapy in UKALL protocols.a Drug
Dose
Route
Regimenb
Dexamethasone Vincristine Methotrexate Methotrexate
6 mg/m2 1.5 mg/m2 20 mg/m2
(OPP)
[1–9] [INVALID Stage]
Original Article
‘Acceptability’ of a new oral suspension formulation of mercaptopurine in children with acute lymphoblastic leukaemia
J Oncol Pharm Practice 0(0) 1–9 ! Nova Laboratories Ltd 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1078155215577808 opp.sagepub.com
Hussain Mulla1,2, Helen Buck3, Lisa Price4, Annie Parry4, Geoff Bell4 and Roderick Skinner5
Abstract Aim: The aim of this questionnaire-based survey was to determine the ‘acceptability’ of XaluprineÕ , a new oral liquid formulation of mercaptopurine, when administered chronically to children during the maintenance treatment phase of acute lymphoblastic leukaemia. Patients and methods: This was a single centre survey of children (aged 3 to 16 years) and their parents at a routine follow-up visit during the maintenance phase of acute lymphoblastic leukaemica treatment. The questionnaire probed for their views on overall acceptability such as taste, smell, incidences of vomiting, ease and willingness to take XaluprineÕ on a daily basis, and utilised a 5-point facial hedonic scale (1 ¼ bad, 5 ¼ good) as well as open/closed questions. Results: Twenty-two children were recruited; 17 (77%) scored taste between 3 and 5 (‘okay’ to ‘good’) and 20 (91%) scored smell between 3 and 5. Only four children (18%) reported an aftertaste. Of the five children (23%) who scored taste as 1 or 2 (‘bad’), three found taking all oral medicines difficult. Six children (27%) reported vomiting, but this was not considered related to XaluprineÕ . Seven children (32%) sometimes complained that they did not want to take XaluprineÕ ; 15 (68%) never complained. In response to the question, ‘How easy is it for you to take XaluprineÕ ?’ 18 children (82%) reported that it was ‘Easy all the time.’ This was more favourable than other oral liquid medicines that they were taking concurrently. Conclusion: The results of this survey show that XaluprineÕ has good overall acceptability in the paediatric population and suggests that XaluprineÕ is an important, alternative, age-appropriate formulation of mercaptopurine.
Keywords Mercaptopurine, palatability, acceptability, acute lymphoblastic leukaemia
Introduction Mercaptopurine is a cornerstone of all maintenance therapy drug regimens for acute lymphoblastic leukaemia (ALL). The efficacy of mercaptopurine for keeping children and adolescents with ALL disease free has been established by a number of national and international trials.1 However, until recently the only approved formulation of mercaptopurine has been a single 50 mg tablet; less than 10% of children with ALL are prescribed doses that match this tablet configuration.2 Moreover, the lack of an age-appropriate mercaptopurine formulation has been an obstacle in treating children, especially young children who are unable to take solid dosage forms.3 XaluprineÕ
1
Nova Laboratories Limited, Leicester, UK Department of Pharmacy, University Hospitals of Leicester, Leicester, UK 3 St Albans, Herts, UK 4 Sir James Spence Institute, Great North Children’s Hospital, Royal Victoria Infirmary, Newcastle UK 5 Department of Paediatric and Adolescent Haematology and Oncology and Children’s BMT Unit, Great North Children’s Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, UK 2
Corresponding author: Hussain Mulla, Department of Pharmacy, Glenfield Hospital, University Hospitals of Leicester, Groby Road, Leicester, LE3 9QP, UK. Email: [email protected]
Downloaded from opp.sagepub.com at UNIVERSITE DE MONTREAL on June 12, 2015
XML Template (2015) [20.3.2015–2:38pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/OPPJ/Vol00000/150015/APPFile/SG-OPPJ150015.3d
(OPP)
[1–9] [INVALID Stage]
2
Journal of Oncology Pharmacy Practice 0(0)
(PurixanÕ in the US) is a newly approved raspberryflavoured oral suspension formulation of mercaptopurine, and offers children, parents and healthcare professionals an alternative to the tablet. For young children in particular, XaluprineÕ is potentially a significant improvement over the existing tablet presentation and addresses compliance issues such as accuracy, flexibility and individualisation of dosing, as well as palatability and acceptability. The palatability of medications (smell, taste, aftertaste and mouth feel), in particular that of liquid formulations used in young children is an important consideration and is believed to play a major role in adherence with drug therapy in paediatrics. Better tasting formulations also make it easier for parents to administer much needed medication.4 The unpleasant taste of antibiotic and antiretrovirals has been widely cited as a common reason for non-adherence, while a number of questionnaire-based studies of compliance with antibiotic treatments in children have reported a correlation between taste and adherence rates.5 The ramifications of poor adherence, namely treatment failure with associated complications, re-treatment, overtreatment and emerging resistance as well as financial costs, are serious healthcare concerns. Specifically in the treatment of children with ALL, mercaptopurine adherence rates below 90% are associated with increased risk of disease relapse (hazard ratio, 3.1, p ¼ 0.04). Moreover, 31% of relapses have been attributed to non-adherence.6,7 Both European and US regulators have specified the need to assess the ‘acceptability’ of paediatric medicinal products as an integral part of pharmaceutical development studies. However, assessment of the acceptability of a dosage form for children is not limited to palatability alone.8 Acceptability is defined as the overall ability of the patient and caregiver (the ‘user’) to use a medicinal product as intended and is determined by both the characteristics of the user (age, ability, disease type and state) and the medicinal product.8 For an oral liquid medicine, this might include: need for modification prior to administration (e.g. reconstitution), palatability, appearance, physical burden of dose (dosing volume), dosing regimen, ease of use of administration device and the primary and secondary container closure system. Moreover, simple taste preference studies involve only a single dose of the test formulation and it is possible that taste perception may change with prolonged administration. It is also unclear whether the results of these single dose studies are predictive of overall acceptability during periods of continuous use.9 Indeed, it is this overall acceptability of a medicine that is perhaps even more critical for a chronically administered medicinal product, such as mercaptopurine, compared to a medicine intended as a short-course,
such as an antibiotic. It is under the conditions of chronic administration that both child and carer need to be sufficiently at ease with the product to ensure high levels of adherence. Studies to assess the acceptability of medicinal products intended for chronic administration should ideally be conducted in the target disease and patient population. The perception of taste of medicines has been shown to be different between adults and children, between healthy and sick children and following exposure to chemotherapy.10,11 From an ethical perspective, it would not be appropriate to conduct acceptability testing of mercaptopurine in healthy volunteer children because of the lack of any benefit to the participant as well as the risk of adverse effects from the medication. Hence, the aim of this questionnaire-based survey of XaluprineÕ was to assess the ‘user’ acceptability during chronic administration in children with ALL, who form the target patient population for this medication.
Patients and methods This study was designed as a non-interventional, paperbased, face-to-face survey of children and their parents during the interim maintenance and maintenance phases of ALL treatment and was conducted at the Great North Children’s Hospital, Newcastle, UK. The survey protocol, questionnaire and consent forms were approved by a local ethics committee and the hospital research and development department. The survey was performed in accordance with the Declaration of Helsinki. Children aged 3 to 12 years with a diagnosis of ALL were eligible. Patients were excluded where children and their parents were both non-English speaking, where children were non-verbal or where the child’s developmental status prevented them from using the survey scales. The centre followed their normal ALL treatment protocols for the prescribing of mercaptopurine therapy as part of combination chemotherapy. The choice between mercaptopurine administration as tablets or XaluprineÕ was based on two criteria: clinician preference (for example, the desire to achieve an accurate dose) and patient/parent preference of dosage form. The survey of XaluprineÕ only recruited those children who had taken the oral liquid for a minimum of four weeks. The number of subjects who were initiated on XaluprineÕ and switched to tablets prior to enrolment was recorded. The questionnaire consisted of three types of questions: open questions, closed questions with categorical responses (e.g. yes/no or choose one of the following), and questions relating to the taste and smell using a 5-point facial hedonic scale. This scale, which allows for indication of preferences by pointing at a pictorial
Downloaded from opp.sagepub.com at UNIVERSITE DE MONTREAL on June 12, 2015
XML Template (2015) [20.3.2015–2:38pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/OPPJ/Vol00000/150015/APPFile/SG-OPPJ150015.3d
(OPP)
[1–9] [INVALID Stage]
Mulla et al.
3
scale of facial expressions, has been commonly employed in palatability studies12,13 (Figure 1). Compared to spontaneous verbal judgment, this method has the advantage of being a more standardised procedure. Studies have shown that children as young as four years can understand and use up to 7-point hedonic scales to indicate whether a substance is pleasing to their taste.9 Since it is routine practice to monitor blood counts regularly during maintenance treatment (typically every 1–2 weeks), the researchers obtained written informed consent of children and their parents (and assent from younger children if appropriate) at one of these visits after the investigator had discussed the survey with the parent and child and provided them the opportunity to read written information about the survey. After consent, a research nurse accompanied each child and parent/carer to a private test area where the study procedures and rating scale were described. The survey sought the views of both parent and child where possible. In the case of very young children where this was not possible, only the parent was surveyed. In each case, the research nurse conducted the survey and recorded the verbal responses to the open and closed questions and where facial hedonic scales were utilised, the parent/ child was asked to indicate their preference by putting their mark on the pictorial scale of facial expressions.
Statistical analysis All data collected were double entered into an Excel database. Demographic data and responses to all
Bad
OK
Good
Figure 1. Visual analogue scale incorporating 5-point facial hedonic scale.
questions were summarised by age group and overall. Categorical data were presented using counts and percentages and continuous variables presented using the mean, standard deviation (SD), median, minimum, maximum and number of subjects (N). All analysis was undertaken using SAS (v.9.1.3).
Results During the period July 2013 to June 2014, a total of 22 patients were enrolled and surveyed: 12 males and 10 females. Of the 22 subjects recruited, 16 subjects were below the age of six (minimum 3.2 years) and six subjects were above the age of six (maximum 10.2 years) (Table 1). In seven subjects (44%) below the age of six years, the survey was completed by seeking the view of parent only; for children >6 years, this only occurred on one (16%) occasion. On all other occasions, the survey was completed by seeking the views of both parent and child together. Since the survey began during the interim period between cessation of UKALL2003 and initiation of UKALL 2011, children recruited into the survey were being treated according to one of three active protocols; UKALL 2003, ALL interim guidelines 2011 and UKALL 2011. Although in some cases XaluprineÕ had been initiated during the interim maintenance phase, all children at the time of the survey were in the maintenance phase of therapy (Table 2). All children had received at least four weeks of XaluprineÕ therapy and the median period of continuous use was 11 weeks. XaluprineÕ is formulated as a 20 mg/ml oral suspension and the dosing volume ranged between 0.5 and 3.5 ml. In all but one child for whom a spoon was used, dosing was achieved using an oral syringe; almost all (95%) of subjects found it ‘very easy’ to use the oral syringe (Table 2). Seventeen out of 22 (77%) subjects scored taste between 3 and 5 (‘okay’ to ‘good’); 20 out of 22 (91%) subjects scored the smell between 3 and 5 (Figure 2). Only four (18%) subjects reported an aftertaste. Of the five subjects who scored taste as 1 or 2
Table 1. Demography.
Age (years) Sex Protocol week of ALL treatmenta Period of continuous XaluprineÕ use at the time of survey XaluprineÕ dose volume (ml)
3 to < 6 years (n ¼ 16)
6 to < 16 years (n ¼ 6)
All patients (n ¼ 22)
4.0 (3.2–5.8) 7 F; 9 M 61 (33–130) 9 (2–38)
7.2 (6.2–10.2) 3 F; 3 M 74 (42–118) 24.5 (3.0–56.0)
5.2 (3.2–10.2) 10 F; 10 M 65 (33–130) 11.0 (2.0–56.0)
2.5 (0.5–3.5)
1.75 (0.9–3.5)
2.5 (0.5–3.5)
a
All subjects were in the maintenance phase; results are presented as median (range).
Downloaded from opp.sagepub.com at UNIVERSITE DE MONTREAL on June 12, 2015
XML Template (2015) [20.3.2015–2:38pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/OPPJ/Vol00000/150015/APPFile/SG-OPPJ150015.3d
(OPP)
[1–9] [INVALID Stage]
4
Journal of Oncology Pharmacy Practice 0(0)
Table 2. Maintenance therapy in UKALL protocols.a Drug
Dose
Route
Regimenb
Dexamethasone Vincristine Methotrexate Methotrexate
6 mg/m2 1.5 mg/m2 20 mg/m2
