Birmingham Children’s Hospital

NHS Foundation Trust

Standard Operating Procedure

Protocol for the use of pegylated GCSF in haematology and

oncology patients

Code Number: Version Number: 1.0 Number of pages: 5

Revision Changes First Issue

Author: Dr Gerard Millen

Job Title: Oncology Clinical Fellow
Dr Jenny Adamski
Reviewer: Consultant paediatric oncologist
Job Title Jason Patel
Oncology pharmacist
Effective Date: 16/2/2021

Review date 16/2/2024

Target Audience Cancer service at BCH/POSCU leads

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NHS Foundation Trust

BACKGROUND

Many oncology protocols recommend the routine use of G-CSF either to facilitate treatment
intensity (high risk neuroblastoma, Ewing sarcoma) or to enable earlier neutrophil recovery
to mitigate actual or potential side effects (post autologous stem cell rescue (ASCR)).
Patients who are having a stem cell harvest prior to ASCR will also require stem cell
mobilisation with G-CSF.

At BCH, we have been using the standard half-life product lenograstim for many years. This
requires a single daily subcutaneous (SC) or intravenous (IV) injection with SC being
preferred due to better efficacy (although this data is extrapolated from adults. This means
that children on some protocols may have in excess of 100 SC injections over the course of
the treatment.

Pegylated G-CSF (pG-CSF) has been used in adults and children for many years.
Pegfilgrastim is licensed for use in children in the USA but not in Europe. It is quite
expensive and a number of biosimilar products are available that are considerably cheaper.
Studies have shown that these biosimilar products have similar efficacy and side effects to
the original product(1).

A number of studies have looked at the safety and efficacy of pG-CSF in children with a
range of malignancies including those receiving standard 3-weekly chemotherapy regimens
and patients receiving so-called interval compressed chemotherapy with 2-weekly regimens.
Although not statistically significant, the studies suggest a trend towards shorter
duration/depth of neutropenia and a reduced incidence of febrile neutropenia. Crucially, the
use of pG-CSF was associated with a very similar side effect profile to standard G-CSF with
bone pain, headaches being the most common side effects(2-9).

1. INDICATIONS FOR PRACTICE

1.1 A number of patient groups at BCH require the routine use of growth factor support
during the course of their treatment for malignancy. The aims of this support are to
reduce the duration and severity of neutropenia as well as the risk of severe bacterial
or opportunistic infections.

1.2 A number of key studies have shown that treatment intensity with shortened intervals
between chemotherapy cycles which can be facilitated by the routine use of G-CSF
can improve outcome for patients.

1.3 G-CSF is also routinely used to encourage earlier neutrophil recovery following high
dose chemotherapy and ASCR.

1.4 The aim of this SOP is to provide evidence based recommendations for the use of
pG-CSF in haematology and oncology patients.

1.5 This SOP applies to patients requiring G-CSF support post chemotherapy who are
treated at BCH or one of the official paediatric oncology shared care units (POSCUs).
Specific exclusions are listed in section 6.

2 AUTHORISED PERSONNEL/TRAINING REQUIRED

2.1 All medical and nursing staff working within cancer services
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2.2 Pharmacy to have oversight of prescribing and supply of medication. SACT review
Group to have oversight of the use of the drug in this patient population.

2.3 No extra training is required for nursing staff as the procedure is the same as for the
administration of G-CSF.

3. ABBREVIATIONS/DEFINITIONS
G-CSF: granulocyte colony stimulating factor
pG-CSF: pegylated granulocyte colony stimulating factor
POSCU: Paediatric Oncology Shared Care Unit
ASCR: Autologous stem cell rescue
CWG: Chemotherapy working group

4. HEALTH AND SAFETY

N/A

5. EQUIPMENT/DOCUMENTATION
N/A

6. PROCEDURE

6.1 Not all patients who require G-CSF will be suitable for pG-CSF. Section 6.2
highlights the patients where the use of pG-CSF should be considered standard of
care. Section 6.3 highlights patients where the use of pG-CSF may be appropriate
but should be discussed with the oncology consultant prior to administration.
Section 6.4 highlights patients where it is not appropriate to use pG-CSF and who
should continue to receive standard G-CSF when required.

6.2 The following patients should receive pG-CSF as standard of care:

6.2.1 Patients requiring regular G-CSF on 3 weekly chemotherapy cycles

6.2.1.1 Give at least 24 hours after the last dose of myelosupressive
chemotherapy and two weeks prior to the next cycle of
chemotherapy
6.2.2 Patients post autologous stem cell rescue
6.2.3 Patients receiving interval compressed chemotherapy as per EuroEwing
protocols
6.2.3.1 Give the day following the completion of chemotherapy

6.3 The following patients may be appropriate for the use of pG-CSF and should be
discussed with a consultant prior to administration:

6.3.1 Patients who are unwell and require G-CSF to aid recovery from post-
chemotherapy complications such as severe sepsis
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NHS Foundation Trust

6.4 The following patients are not suitable for the use of pG-CSF and should continue
to receive standard G-CSF:

6.4.1 Patients with high risk neuroblastoma receiving rapid COJEC

chemotherapy
6.4.2 Patients who are due to receive G-CSF for stem cell mobilisation. This
group of patients should receive standard G-CSF.

6.5 There are currently no plans to introduce pG-CSF for other patients within the
Blood, Stem cell transplantation and Cancer service though this may be the subject
of review. Any patients not listed in sections 6.2-6.4 who require G-CSF support
should receive standard G-CSF unless a consultant has made an individual patient
decision weighing up the risks and benefits of pG-CSF versus standard G-CSF.

6.6 DOSE

6.6.1 For patients receiving pG-CSF, the recommended dose is 0.1mg/kg

(maximum single dose 6mg). Patients should receive the first dose of pG-
CSF in a hospital setting but subsequent doses may be delivered in the
community with the support of the community nursing team where
appropriate

6.7 The SACT (chemotherapy) nursing team and SACT review group will maintain an
oversight of the use pG-CSF

6.7.1 The SACT(chemo) team will keep a list of patients that receive pG-CSF on
behalf of the SACT review group. Any incidences of unexpected
chemotherapy delay or side effects following the use of pG-CSF will be
monitored.
6.7.2 After an initial 6 months of routine use, the CWG will provide a report on
total use to the Drugs and Therapeutics Committee

7. FURTHER INFORMATION

7.1 Contact details

7.1.1 SACT (chemotherapy) team via ward 18
7.1.2 Pharmacy chemotherapy team

8. REFERENCES

1. Caselli D, Cesaro S, Arico M. Biosimilars in the management of neutropenia: focus on

filgrastim. Biologics. 2016;10:17-22.
2. Accord. Pelgraz 6 mg solution for injection in pre-filled syringe 2019 [Available from:
https://www.medicines.org.uk/emc/product/9531/smpc#gref.
3. Andre N, Kababri ME, Bertrand P, Rome A, Coze C, Gentet JC, et al. Safety and efficacy
of pegfilgrastim in children with cancer receiving myelosuppressive chemotherapy.
Anticancer Drugs. 2007;18(3):277-81.
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4. Borinstein SC, Pollard J, Winter L, Hawkins DS. Pegfilgrastim for prevention of

chemotherapy-associated neutropenia in pediatric patients with solid tumors. Pediatr Blood
Cancer. 2009;53(3):375-8.
5. Cesaro S, Nesi F, Tridello G, Abate M, Panizzolo IS, Balter R, et al. A randomized, non-
inferiority study comparing efficacy and safety of a single dose of pegfilgrastim versus daily
filgrastim in pediatric patients after autologous peripheral blood stem cell transplant. PLoS
One. 2013;8(1):e53252.
6. Cesaro S, Zanazzo AG, Frenos S, Luksch R, Pegoraro A, Tridello G, et al. A Phase II
study on the safety and efficacy of a single dose of pegfilgrastim for mobilization and
transplantation of autologous hematopoietic stem cells in pediatric oncohematology patients.
Transfusion. 2011;51(11):2480-7.
7. Fox E, Widemann BC, Hawkins DS, Jayaprakash N, Dagher R, Aikin AA, et al.
Randomized trial and pharmacokinetic study of pegfilgrastim versus filgrastim after dose-
intensive chemotherapy in young adults and children with sarcomas. Clin Cancer Res.
2009;15(23):7361-7.
8. Milano-Bausset E, Gaudart J, Rome A, Coze C, Gentet JC, Padovani L, et al.
Retrospective comparison of neutropenia in children with Ewing sarcoma treated with
chemotherapy and granulocyte colony-stimulating factor (G-CSF) or pegylated G-CSF. Clin
Ther. 2009;31 Pt 2:2388-95.
9. Umoru GO, Zaghloul H, El-Rahi C, Ensor JE. Evaluation of efficacy and safety of
pegfilgrastim when given less than two weeks from dose-dense chemotherapy regimens. J
Oncol Pharm Pract. 2020:1078155220948937.