Dr David Eedes, Clinical Oncology Advisor at ICON, unpacks some of the key elements of ASCO’s updated guidelines on the use of of hematopoietic colony-stimulating factors (CSFs), a treatment option for neutropenia.
The American Society of Clinical Oncology (ASCO) released an updated version of its Clinical Practice Guidelines on the use of hematopoietic colony-stimulating factors (CSFs), a treatment option for neutropenia. The update is based on a systematic review of randomised clinical trials, meta-analyses, and systematic reviews conducted between October 2005 and September 2014.
These guidelines are intended to address the use of CSFs in clinical practice and I think are a helpful reminder of the benefits and limitations of this expensive agent in routine practice.
The ASCO Key Guideline Recommendations (bold areas ICON insertions):
- In patients with a greater than 20% risk of febrile neutropenia, primary prophylaxis with G-CSF with first and subsequent cycles of chemotherapy is recommended. The guidelines also note that regimens that do not require G-CSF and are equally effective should be considered.
- In patients with a neutropenic complication from a previous cycle of chemotherapy (without primary prophylaxis) and reduction or delay in treatment that would alter outcome/survival, G-CSF is recommended for secondary prophylaxis. The authors note, however, that a reduction/delay may be reasonable in many situations.
- In patients with afebrile neutropenia, G-CSF should not be used routinely.
- Adjunctive treatment of G-CSF with antibiotics should not be routinely used for patients with febrile neutropenia. However, patients with febrile neutropenia who are considered at risk for poor outcomes or infection related-complications may be considered.
- The authors note that use of G-CSF with dose-dense regimens should only be considered when involved in a well-designed clinical trial or with support of convincing efficacy data.
- In order to mobilize peripheral-blood progenitor cells, G-CSF may be used with plerixafor, after chemotherapy, or alone.
- To lessen the duration of severe neutropenia, G-CSF should be given after autologous stem-cell transplants.
- To lessen the duration of severe neutropenia, G-CSF may be given after allogeneic stem-cell transplants. Since the 2006 update, reports of increased risk of grade 2 to 4 graft-versus-host disease with G-CSF use after allogeneic transplantation have not been confirmed. The researchers note that the benefits seem to be modest with the limited amount of data.
- Patients age 65 or older, particularly those with comorbidities, with aggressive forms of diffuse lymphoma treated with curative chemotherapy should be considered for CSF prophylaxis.
- In paediatric patients, G-CSF for primary prophylaxis is considered reasonable in patients at high risk for febrile neutropenia. Likewise, the guidelines note that secondary prophylaxis should be limited to patients who are high risk.
- G-CSF should be used in paediatric patients to facilitate dose-intense chemotherapy regimens that are known to have survival benefits (Ewing sarcoma).
- The guidelines do not recommend using G-CSF in non-relapsed acute myeloid leukemia or non-relapsed acute lymphocytic leukemia in paediatric patients without infection
- There were no additional data to support a change in recommendation on treatment choice for treatment-related neutropenia. Patient’s clinical situation, convenience, and cost are factors considered in the agent choice.
- The authors note a moderate recommendation for use of G-CSF or pegylated G-CSF in patients exposed to lethal doses of total-body radiotherapy without evidence of impending death from organ injury.
The use of G-CSF and pegylated G-CSF has gone up markedly in recent years, especially in the US. While we at ICON believe these drugs are useful in the correct clinical setting, we would recommend that the above guidelines are kept in mind when making decisions about the appropriate use of G-CSF.
What should not be forgotten is that these agents do not come without cost, both financial and toxic. It is also important to note that for prophylaxis, G-CSF should not be used sooner than 24 hours after completion of chemotherapy infusion and preferably not for 14 days prior to the next infusion. This makes using it in 14 day chemotherapy cycles problematic.
Some reported toxicity:
- Pulmonary toxicity with Bleomycin containing regimens esp. ABVD in HD.
- Worse outcomes with concurrent chemoradiotherapy especially squamous carcinoma of the head and neck where one clinical trial showed a significantly reduced loco-regional tumour control and in small cell lung cancer where there was a marked increase in thrombocytopenia in patients on chemoradiation.
- Observational studies have shown that the use of G-CSF during chemotherapy for other malignancies is associated with a small but real increased risk of therapy-related AML and MDS. Systematic review of 25 trials showed that the use of G-CSF increases the risk of a therapy-related myeloid neoplasm but the absolute magnitude of the risk is small.
Smith T, Bohlke K, Lyman G, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update. See comment in PubMed Commons belowJ Clin Oncol. 2015 Oct1;33(28):3199-212. doi: 10.1200/JCO.2015.62.3488. Epub 2015 Jul 13.