Christian Jackisch

Multivariate analysis of febrile neutropenia occurrence in patients with non-Hodgkin lymphoma: data from the INC-EU Prospective Observational European Neutropenia Study

Myelosuppression, particularly febrile neutropenia (FN), are serious dose‐limiting toxicities that occur frequently during the first cycle of chemotherapy. Identifying patients most at risk of developing FN might help physicians to target prophylactic treatment with colony‐stimulating factor (CSF), in order to decrease the incidence, or duration, of myelosuppression and facilitate delivery of chemotherapy as planned. We present a risk model for FN occurrence in the first cycle of chemotherapy, based on a subgroup of 240 patients with non‐Hodgkin lymphoma (NHL) enroled in our European prospective observational study. Eligible patients had an International Prognostic Index of 0–3, and were scheduled to receive a new myelosuppressive chemotherapy regimen with at least four cycles. Clinically relevant factors significantly associated with cycle 1 FN were older age, increasing planned cyclophosphamide dose, a history of previous chemotherapy, a history of recent infection, and low baseline albumin (<35 g/l). Prophylactic CSF use and higher weight were associated with a significant protective effect. The model had high sensitivity (81%) and specificity (80%). Our model, together with treatment guidelines, may rationalise the clinical decision of whether to support patients with CSF primary prophylaxis based on their risk factor profile. Further validation is required.

Risk factors for chemotherapy-induced neutropenia occurrence in breast cancer patients : data from the INC-EU Prospective Observational European Neutropenia Study.

BackgroundChemotherapy-induced neutropenia (CIN) places patients at risk of life-threatening infections. While reduction of chemotherapy dose or delay of the subsequent treatment cycle and, consequently, reduction of relative dose intensity (RDI) may limit myelotoxicity, these actions can also impact adversely on treatment outcome and should be avoided in adjuvant settings.Patients and methodsBased on data from 444 breast cancer patients in the INC-EU Prospective Observational European Neutropenia Study, we have evaluated patient-specific and treatment-specific factors that impact on the incidence of grade 4 CIN (absolute neutrophil count <0.5 × 109/L), either during the first or in any cycle of (neo)adjuvant chemotherapy, across a range of regimens and doses.ResultsUsing multivariate logistic regression analysis, risk factors for grade 4 CIN were identified as older age, lower weight, higher planned dose intensity of doxorubicin, epirubicin, or docetaxel, higher number of planned cycles, vascular comorbidity, lower baseline white blood cell count, and higher baseline bilirubin. Use of colony-stimulating factor before a neutropenic event occurred, dose delays, and dose reductions were protective against grade 4 CIN.ConclusionsBy identifying risk factors for grade 4 CIN, CSF prophylaxis may be appropriately targeted to prevent low RDI in patients treated with curative intent.

Delivering optimal adjuvant chemotherapy in primary breast cancer: the role of rHuG-CSF

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