Download (g-csf) in adult patients with solid tumours

North Wales Cancer Network
Guidelines for the use of colony stimulating factor (G-CSF) in adult
patients with solid tumours
1.
Background
Recombinant human granulocyte colony stimulating factor (rhG-CSF) stimulates the production
of neutrophils. It may reduce the duration of chemotherapy-induced neutropenia and reduce the
incidence of associated sepsis. There is no evidence that it improves overall survival.
Treatment with recombinant growth factors should only be prescribed by those experienced in
their use.
Filgrastim (unglycosylated rhG-CSF) and lenogastrim (glycosylated rhG-CSF) have similar
actions.
Pegfilgastrim is a polyethylene glycol-conjugated (“pegylated”) derivative of filgastrim. Pegylation
increases the duration of filgastrim activity.
2.
Indications
2.1
Primary prophylactic G-CSF administration
The use of G-CSF for primary prophylaxis is not routinely recommended unless the expected
risk of febrile neutropenia (FN) is ≥ 20%
Primary prophylaxis may be justified in patients at higher risk of infectious complications due to
special circumstances. E.g.






2.2
Elderly patients (aged 65 and over)
Pre-existing neutropenia
Extensive prior chemotherapy
Precious irradiation to pelvis or other areas containing large amounts of bone marrow.
A history of recurrent febrile neutropenia while receiving earlier chemotherapy or similar or
lesser dose-intensity.
Conditions that potentially enhance the risk of serious infection. (poor performance status,
active infection, decreased immune function).
Secondary prophylactic G-CSF administration
Secondary prophylaxis is used to maintain dose intensity, particularly in lymphoma and adjuvant
breast cancer treatment following an episode of sepsis or to prevent treatment delays.
In the absence of clinical data, or other compelling reasons to maintain chemotherapy doseintensity, dose reductions should be considered following episodes of febrile neutropenia or
prolonged neutropenia with previous cycles, rather than secondary prophylaxis with growth
factors, particularly if chemotherapy is not being given with curative intent.
2.3
Afebrile patients
Growth factors should not be routinely used for afebrile neutropenic patients.
2.4
Febrile patients
G_CSF should not be routinely used as an adjunct to antibiotic therapy in the treatment of
uncomplicated fever and neutropenia but should be considered in patients with poor prognostic
factors e.g:
 Pneumonia
 Multi-organ dysfunction
 Hypotension
 Invasive fungal infection
 Profound neutropenia ANC < 0.1 x 109/L)
 Age > 65 or those with post treatment lymphopenia
2.5
G-CSF for patients receiving concurrent chemotherapy and irradiation
G-CSF should be avoided in patients receiving concomitant chemotherapy and radiotherapy,
particularly involving the mediastinum (ASCO guidelines in JCO 2000, and update in JCO 2006).
In the absence of chemotherapy, in patients receiving radiotherapy to large areas, the
therapeutic use of G-CSF may be considered if prolonged delays to secondary for neutropenia
are expected.
Step 1
Assess frequency of FN associated with planned chemotherapy
regimen
FN risk ≥ 20%
FN risk 10-20%
FN risk <
10%
Step 2
Assess factors that increase the frequency/risk of FN
High risk
Age > 65 years
Increased risk
(level I and II
evidence)
Advanced disease
History of prior FN
No antibiotic prophylaxis, no G-CSF use
Other factors
(level III and
IV evidence)
Poor performance and /or nutritional status
Female gender
Haemoglobin <12g/dL
Liver, renal or cardiovascular disease
Step 3
Define the patient’s overall FN risk for planned chemotherapy
regimen
Overall FN risk ≥20%
Prophylactic G-CSF
recommended
Overall FN risk < 20%
G-CSF use not
indicated
EORTC guidelines for the use of G-CSF to reduce the incidence of chemotherapy-induced febrile neutropenia in
adult patients with lymphomas and solid tumours
European Journal of Cancer 42 (2006) 2433 - 2453
3.
Preparations
Filgrastim:
Cytotoxic induced neutropenia – Dose is 0.5 million units (5 micrograms) per kg
daily by subcutaneous injection started not less than 24 hours after cytotoxic
chemotherapy, continued until the neutrophil count has recovered to the normal
range.
Lenograstim: Cytotoxic induced neutropenia – Dose is 19.2 million units (150 micrograms) per
m2 daily, by subcutaneous injection, started not less than 24 hours after cytotoxic
chemotherapy, continued until the neutrophil count has recovered to the normal
range.
Pegfilgrastim: Prevention of cytotoxic induced neutropenia – Dose 6mg (0.6ml) once only for
each chemotherapy cycle, starting 24 hours after chemotherapy.
Normally only considered in patients requiring extended protection from
neutropenia, for instance if previous chemotherapy has resulted in extended use
of G-CSF support, or for certain lung and lymphoma chemotherapy regimens
known to cause prolonged neutropenic episodes.
4.
Cautions
Recombinant human growth factors are to be used with caution in patients with
premalignant or malignant myeloid conditions. Full blood counts including differential
white cell and platelet counts should be monitored.
Treatment should be discontinued in patients who develop signs of pulmonary infiltration
Spleen size should be monitored as splenic rupture following the administration of
G-CSF has been reported.
Recombinant human growth factors are not recommended in pregnancy or breastfeeding.
5.
Side-effects
Include gastro-intestinal disturbances, anorexia, headache, asthenia, fever, muscular-skeletal
pain, bone pain, rash, alopecia, injection site reactions and leocytosis.
Less frequent side effects include chest pain, hypersensitivity reactions and arthralgia.
There have been reports of pulmonary infiltrates leading to acute respiratory distress syndrome.
6.
References
Ozer H.et al. 2000 update of recommendations for the use haemopoietic colony stimulating
factors: evidence- based clinical practice guidelines. Journal of Clinical Oncology, 2000; 18:
3558-3585
Smith TJ. et al. 2006 update of recommendations for the use of white blood cell growth factors:
an evidence-based clinical practice guideline. Journal of Clinical Oncology, 2006; 24 (19): 31873205
Aapro MS. et al. EORTC guidelines for the use of granulocyte-colony stimulating factor to
reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with
lymphomas and solid tumours. 2006; 42: 2433-2453
British National Formulary no 53 (March 2007)
7.
Approval
Agreed by Haematology MDT:
27.09.07
To be reviewed by:
27.09.10 or sooner as required