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  1. Introduction 3
  1. Introduction

This guidance has been produced to make recommendations for the use of Granulocyte Colony Stimulating Factors in adult patients undergoing chemotherapy for cancer.This document aims to combine up to date research, current thinking, and local expert opinion to generate Network Guidelines.

  1. Background

Bone marrow suppression is among the most common toxicities encountered as a result of chemotherapeutic treatment of malignancy. In addition to life-threatening complications arising from neutropenia, thrombocytopenia and anaemia, dose reductions and dose delays may compromise treatment outcomes. Guidelines for the use of G-CSF and GM-CSF have been published by the American Society of Clinical Oncology, the British Committee for Standards in Haematology and the National Comprehensive Cancer Network clinical guidelines.

  1. Indications

The use of G-CSF may be indicated for the following:

  1. Primary prophylaxis
  1. Secondary prophylaxis
  1. Therapeutic use
  1. As an adjunct to allogeneic or autologous progenitor cell transplantation
  1. Primary prophylaxis

G-CSF is not recommended with most first line therapies.Clinical trial data supports the use of CSF when the risk of febrile neutropenia (FN) is in the range of 20% or higher. Examples of regimens with a high risk of FN include:

Haematology:DHAP, ESHAP, R-ICE, CODOX- M / IVAC, Hyper C-VAD and CHOP 14

Oncology:BEP 360 (germ cell), BEP 500 (germ cell), EP,High dose Ifosfamide regimens for Sarcoma, FEC-T (breast) TPF (H&N).

Primary prophylaxis may also be justified in patients at higher risk of infectious complications due to special circumstances. For example:

  • In patients with diffuse aggressive lymphoma aged > 65 years
  • Pre-existing neutropenia,
  • Extensive prior chemotherapy,
  • Previous irradiation to the pelvis or other areas containing large amounts of bone marrow.
  • A history of recurrent febrile neutropenia while receiving earlier chemotherapy of similar or lesser dose –intensity.
  • Conditions that potentially enhance the risk of serious infection. (Poor performance status, active infection, decreased immune function).
  1. Secondary prophylaxis

Secondary prophylaxis treatment can be initiated in chemotherapy cycles after an occurrence of chemotherapy-induced prolonged neutropenia or febrile neutropenia, with or without dose delay on this account, in a setting where clinical data support the maintenance of dose intensity.

For potentially curative treatment or in tumours where it is felt that dose reduction/dose delay for subsequent cycles of chemotherapy may compromise outcome.

Secondary prophylaxis should NOT be used in the case of palliative chemotherapy unless neutropenic sepsis occurs after a suitable dose reduction has been made.

Possible clinical contexts for secondary prevention might include:-

  • Adjuvant chemotherapy
  • Chemotherapy for germ cell tumours
  • Elderly patients with high grade NHL
  • Dose escalated or intensive schedules for Hodgkin’s and Non-Hodgkin’s lymphoma
  • AML following consolidation treatment
  • AML following induction treatment if appropriate to reduce hospital stay and antibiotic use
  • ALL following intensive phases of therapy
  • In patients who have previously experienced episodes of complicated neutropenia
  1. Therapeutic use

G-CSF should NOT be routinely prescribed for the treatment of patients with uncomplicated FN (duration of fever <10 days) or afebrile neutropenia.

G-CSF may be considered for the supportive treatment of patients with a high risk of infection-associated complications and severe FN (ANC <0.1 x 109/L). G-CSF should continue until ANC >1.0 x 109/L for 2 consecutive days. High risk features include:

  • Uncontrolled primary disease
  • Pneumonia
  • Clinically unwell with signs such as hypotension or organ dysfunction indicating potential risk of septic shock
  • Expected prolonged duration of neutropenia (>10 days)
  • Proven or suspected invasive fungal infection
  • Age >65 yrs old
  1. Use of GCSF in Progenitor Stem Cell Transplantation

Mobilisation of Peripheral Blood Stem Cells (PBSC)

Evidence clearly shows an indication for GCSF in the mobilisation of peripheral blood stem cells. It increases the number of progenitor cells mobilised into and acquired from thecirculation. This relieves the demand for leucophoresis procedures, potentially speeds uphaematological recovery after the transplant and shortens hospitalisation. GCSF may improve the PBSC product, as documented in patients with haematologicalmalignancies and in patients with rheumatoid arthritis.

Post-PBSC (Allogeneic and Autologous) and Bone Marrow Transplant (BMT)

GCSF can be used to reduce the time required for neutrophil regeneration. If it isadministered within five days of autologous PBSC reinfusion, it can reduce the duration ofneutropenia. The decision to give GCSF after a bone marrow transplant should be made bya consultant haematologist or medical oncologist only. Patients should receive GCSF fromday five until bone marrow recovery.

  1. Dose and Administration

Doses should be rounded to the nearest vial or pre-filled syringe size.

G-CSF should not be administered within 24 hours of cytotoxic chemotherapy. The recommended start date is 3 days after the administration of chemotherapy. Treatment should be continued for 7-10 days or until neutrophils >1.0 x 109 /L.

  1. Product Choice

Products should be prescribed by brand to avoid confusion. The recommendations below are based on evidence, product license, national guidance and cost. These recommendations will be reviewed on a regular basis.

Filgrastim (Ratioagrastim®)

1st line for treatment and prophylaxis of chemotherapy induced neutropenia.

Dose:S/C 0.5MU/kg/day after myelosuppressive chemo until neutrophil count in acceptable range (usually 7-10 days).Please refer to SPC for further details.

Lenograstim (Granocyte®)

PBSC mobilization and to reduce period of neutropenia post re-infusion.

Mobilisation of PBSC:S/C or IV infusion 19.2 MIU/m2 /day for 4-6 days.

Please refer to SPC for further details.

Pegfilgrastim (Neulasta®)

Restricted for use in patients where assistance from a community nurse would be required for administration or patients with needle phobia.

Dose: S/C 6 mg (Pre-filled syringes 6 mg in 0.6ml) per chemotherapy cycle administered 24 hours after chemotherapy.Please refer to SPC for further details.

  1. Adverse Effects

G-CSF is usually well tolerated; occasionally, localized reactions may be observed at the injection site.

  • Musculoskeletal pain and headaches may be a problem in some patients. Patients should be warned of these effects. This can be minimised by the use of mild analgesia e.g. Paracetamol, Non-Steroidal Anti-Inflammatory Drugs or mild opioids.
  • Other side effects are rare but may include transient hypotension, thrombocytopenia, disturbances in liver enzymes and serum uric acid, splenic enlargement. For a full list of potential side effects refer to product literature.
  • Pharmacists, doctors and nurses are reminded to report serious, rare, unusual or unexpected Adverse Drug Reaction’s using the Yellow Card Scheme.

References

  1. BCSH. Guidelines on the use of Colony Stimulating Factors in Haematological Malignancies. British Journal of Haematology 2003, 123 22-33.
  2. 2006 Update of Recommendations for the Use of White Blood Cells Growth Factors: Evidence-based, Clinical Practice Guidelines. ASCO Special Article Journal of Clinical Oncology. Vol 24, No 19 (May 15), 2006
  3. NCCN Clinical Practice Guidelines – Myeloid growth Factors V1.2009
  4. AWMSG Final Appraisal Report for Pegfilgrastim (Neulasta®)Advice No: 1508 – August 2008
  5. BNF edition no 57 March 2009
  6. SPC’s for Granocyte®, Ratioagrastim®, Neulasta®
  7. AWMSG Final Appraisal Report for Filgrastim (Ratiograstim®▼) for the treatment of neutropenia. Advice No: 1609 – August 2009

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Network GCSF guidelines V1.0 T. Parry August 2009