Growth Factor Support During Chemotherapy

Granulocyte colony-stimulating factors shorten neutropenia and lower the risk of febrile neutropenia, allowing chemotherapy to be given on schedule at full dose. They are used to prevent febrile neutropenia in selected patients, not routinely in every cycle. Erythropoiesis-stimulating agents have a separate and narrower role.

Risk-based use.

• Primary prophylaxis: expected febrile neutropenia risk of 20% or more (for example dose-dense anthracycline regimens, docetaxel combinations, high-dose regimens for lymphoma or testicular cancer).
• Consider at 10 to 20% with patient risk factors: age over 65, prior chemotherapy or radiotherapy, poor performance status, HIV infection, kidney or liver impairment, low albumin, open wounds or active infection, and low baseline counts.
• Secondary prophylaxis: after a febrile neutropenia episode or dose-limiting neutropenia in a previous cycle when dose reduction would harm outcome.

Short-acting (filgrastim or biosimilar). 5 micrograms/kg subcutaneously once daily (300 micrograms if under 70 kg, 480 micrograms if 70 kg or more), starting 24 to 72 hours after the last chemotherapy dose and continuing until neutrophils recover (post-nadir count over 2 to 3 x 10⁹/L), usually 5 to 10 days.

Long-acting (pegfilgrastim or biosimilar). 6 mg subcutaneously once, given 24 to 72 hours after chemotherapy ends. Do not give within 14 days before the next cycle or with weekly regimens.

Do not give. Within 24 hours before a chemotherapy dose, during chest radiotherapy, or on the same day as fluorouracil.

Treatment of established neutropenic fever. Antibiotics are the treatment; add filgrastim only in high-risk patients (sepsis, pneumonia, fungal infection, expected neutropenia over 10 days, age over 65).

Erythropoiesis-stimulating agents (specialist). For chemotherapy anaemia with haemoglobin under 10 g/dL in non-curative treatment: epoetin alfa 150 units/kg subcutaneously 3 times weekly (or darbepoetin 2.25 micrograms/kg weekly), aiming for haemoglobin 10 to 12 g/dL; stop at 12 g/dL. Avoid in curative treatment, in uncontrolled hypertension, and in patients with prior thrombosis. Check iron stores and give iron.

Kidney and liver impairment. No dose change.

Children. Filgrastim 5 micrograms/kg daily; pegfilgrastim 100 micrograms/kg (maximum 6 mg) once for children under 45 kg.

Sickle cell disease and trait. Risk of sickle crisis; use with caution and hydration.

Pregnancy and breastfeeding. Limited data; use only if benefit outweighs risk. Filgrastim is likely compatible with breastfeeding because it is poorly absorbed orally.

Adverse effects. Bone pain (paracetamol 1 g, or naproxen 500 mg twice daily with food, plus loratadine 10 mg daily), injection site reaction, splenic rupture (left upper quadrant or shoulder tip pain), leucocytosis, allergic reaction, capillary leak and acute respiratory distress syndrome (rare).

Regional. Growth factors are costly and uneven in supply. Use them for patients with the highest febrile neutropenia risk or after a first episode, and avoid dose-dense regimens. Biosimilar filgrastim is the usual choice.

Monitoring. Full blood count before each cycle and, when using daily filgrastim, once or twice weekly until neutrophils pass the nadir. Spleen examination if abdominal pain.

Stopping. Stop filgrastim when post-nadir neutrophils exceed 10 x 10⁹/L on one count or 2 to 3 x 10⁹/L on two counts.

Escalate. Review for splenic rupture, pulmonary infiltrates or fever with a rising count; stop the growth factor and assess urgently. Reassess indication each cycle and stop if the regimen changes to lower risk.