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Most patients with operable breast cancer now receive postoperative medical treatment in the form of adjuvant chemotherapy, hormone manipulation or both. These additional interventions have led to a significant improvement in disease-free survival and overall survival. Clinical trials suggest that total chemotherapy dose delivered and dose intensity both affect long-term clinical outcomes, yet clinical practice audits conducted in Europe and the USA show that dose reductions and delays are widely applied when haematological toxicities such as neutropenia occur. In order to reduce the risk of neutropenic complications and help deliver chemotherapy planned dose on time, targeted use of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) in breast cancer patients is recommended. The availability of neutropenia risk prediction models and the first once-per-cycle, fixed-dose rHuG-CSF (pegfilgrastim), will allow more patients to benefit from receiving their planned chemotherapy dose on time, and enable the use of new dose-dense chemotherapy strategies in the adjuvant treatment of primary breast cancer. These hold the prospect of further improving chemotherapy treatment outcomes. [Copyright &y& Elsevier]

Treatment- and disease-related neutropenia are associated with a number of negative clinical effects such as febrile neutropenia, documented infection, hospitalisation for infection-related morbidity, infection-related mortality, and decreased ability to administer the planned chemotherapy dose on schedule. Reductions or delays in dosage have the ability to jeopardise the effectiveness of treatment by lowering response rates. Not only are clinical outcomes adversely affected, but these complications can have a negative influence on patient quality of life. Filgrastim is a haematopoietic growth factor that primarily acts to stimulate the proliferation and differentiation of neutrophil progenitor cells. Filgrastim is capable of reducing the incidence and severity of neutropenia and the complications that accompany it in patients with cancer or HIV infection. Although there are few data evaluating the effect of treatment with granulocyte colony-stimulating factor on quality of life, it is assumed that the benefits would be seen through both the reduction of treatment-related complications and the enhanced potential for long-term disease control. A new, longer-acting form of filgrastim is now available that has the potential to simplify the management of neutropenia and further improve patient quality of life by decreasing the number of necessary injections. Additional prospective controlled trials that contain quality-of-life issues as endpoints are needed . [ABSTRACT FROM AUTHOR]

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (⩾65years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (⩾20%) or intermediate (10–20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10–20% of patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications where indicated. Filgrastim biosimilars are also approved for use in Europe. While other forms of G-CSF, including biosimilars, are administered by a course of daily injections, pegfilgrastim allows once-per-cycle administration. Choice of formulation remains a matter for individual clinical judgement. Evidence from multiple low level studies derived from audit data and clinical practice suggests that some patients receive suboptimal daily G-CSFs; the use of pegfilgrastim may avoid this problem. [Copyright &y& Elsevier]

Abstract: Granulocyte colony-stimulating factors (G-CSFs) reduce febrile neutropaenia (FN) incidence but may be used inconsistently in current practice (CP). This study compared the efficacy of pegfilgrastim primary prophylaxis (PPP) with CP neutropaenia management in breast cancer. Individual patient data (N =2282) from 11 clinical trials and observational studies using chemotherapy regimens with ⩾15% FN risk and PPP (6mg, all cycles) or CP (no G-CSF or any cycle G-CSF/pegfilgrastim) were included in an integrated analysis. Most patients received docetaxel-containing regimens. A generalised linear mixed model was fitted (N =2210). Neutropaenia prophylaxis (PPP versus CP), age and disease stage influenced the incidence of FN. Overall, FN was less frequent with PPP than with CP (odds ratio [OR]: 0.124; 95% confidence interval [CI]: 0.08, 0.194; P <0.0001). Odds for cycle 1 FN, dose reductions⩾15% and FN-related hospitalisation were also significantly lower with PPP. These data support PPP in breast cancer patients receiving chemotherapy with moderately high/high FN risk. [Copyright &y& Elsevier]

Abstract: Chemotherapy-induced neutropenia is not only a major risk factor for infection-related morbidity and mortality, but is also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact on the success of treatment, particularly when treatment intent is either curative or to prolong survival. The incidence of severe or FN can be reduced by prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim, lenograstim or pegfilgrastim. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. While several academic groups have produced evidence-based clinical practice guidelines in an effort to standardise and optimise the management of FN, there remains a need for generally applicable, European-focused guidelines. To this end, we undertook a systematic literature review and formulated recommendations for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. We recommend that patient-related adverse risk factors such as elderly age (⩾65 years), be evaluated in the overall assessment of FN risk prior to administering each cycle of chemotherapy. In addition, when using a chemotherapy regimen associated with FN in >20% patients, prophylactic G-CSF is recommended. When using a chemotherapy regimen associated with FN in 10–20% patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Finally, studies have shown that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications, where indicated. [Copyright &y& Elsevier]