Support Care Cancer DOI 10.1007/s00520-014-2459-x
REVIEW ARTICLE
Granulocyte colony-stimulating factors as prophylaxis against febrile neutropenia Sol Cortés de Miguel & Miguel Ángel Calleja-Hernández & Salomón Menjón-Beltrán & Inmaculada Vallejo-Rodríguez
Received: 9 June 2014 / Accepted: 22 September 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Myelosuppression secondary to chemotherapy remains a serious adverse effect of cancer therapy that causes high morbidity and mortality. Several current European and American guidelines recommend consideration of primary prophylaxis with colony-stimulating factors (CSFs) when the risk of febrile neutropenia is higher than 20 %. The main factors associated with a high risk of febrile neutropenia include the chemotherapy regimen, tumor type, and patientrelated factors such as old age and/or comorbidities. The purpose of this paper is to summarize the most relevant clinical trials and updated recommendations of the main guidelines on the role of granulocyte colony-stimulating factors (G-CSFs) in febrile neutropenia, examining whether the combination of G-CSF with chemotherapy improves overall survival. Future directions for G-CSF use are also discussed. Keywords Granulocyte colony-stimulating factors . Febrile neutropenia . Cytotoxic chemotherapy . Myelosuppression . Filgrastim . Pegfilgrastim
Introduction Myelosuppression represents the main dose-limiting toxicity associated with systemic cancer chemotherapy. Febrile neutropenia (FN) remains a major threat to patients treated with S. Cortés de Miguel (*) : M. Á. Calleja-Hernández : I. Vallejo-Rodríguez Pharmacy Service, UGC Intercentro-Interniveles, University Hospital Virgen de Las Nieves, Av de las Fuerzas Armadas, 2, 18014 Granada, Spain e-mail: [email protected] S. Menjón-Beltrán Department of Gynecology and Obstetrics, University Hospital Virgen de las Nieves, Granada, Spain
chemotherapy, resulting in impaired quality of life, increased risk of infections, and even death [1–4]. Chemotherapyinduced FN may also result in dose delays and reductions, which may compromise treatment effectiveness and worsen patient outcomes [5, 6]. This may impact on the success of treatment, particularly when treatment intent is either curative or to prolong survival [7]. The role of neutropenia in increasing the risk of serious infection in patients with cancer receiving cytotoxic chemotherapy was first recognized in the mid-1960s. In a study with patients whose absolute neutrophil count (ANC) remained below 1.0×109/L for 7 days, the probability of developing an infection was more than 50 %, and the risk of infection approached 100 % with longer duration of severe neutropenia [8]. This risk can be modified by alterations of physical defense barriers (oral mucositis or the presence of indwelling intravenous catheters), the status of the patient’s cellular and humoral immune system, and the patient’s endogenous microflora or organisms acquired in the hospital, clinic, or community [9]. The administration of chemotherapy can not only decrease the number of neutrophils but also produce chemotactic and phagocytic defects. The ANC is generally used to classify the severity of neutropenia as follows [10]: grade 1: ANC
REVIEW ARTICLE
Granulocyte colony-stimulating factors as prophylaxis against febrile neutropenia Sol Cortés de Miguel & Miguel Ángel Calleja-Hernández & Salomón Menjón-Beltrán & Inmaculada Vallejo-Rodríguez
Received: 9 June 2014 / Accepted: 22 September 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Myelosuppression secondary to chemotherapy remains a serious adverse effect of cancer therapy that causes high morbidity and mortality. Several current European and American guidelines recommend consideration of primary prophylaxis with colony-stimulating factors (CSFs) when the risk of febrile neutropenia is higher than 20 %. The main factors associated with a high risk of febrile neutropenia include the chemotherapy regimen, tumor type, and patientrelated factors such as old age and/or comorbidities. The purpose of this paper is to summarize the most relevant clinical trials and updated recommendations of the main guidelines on the role of granulocyte colony-stimulating factors (G-CSFs) in febrile neutropenia, examining whether the combination of G-CSF with chemotherapy improves overall survival. Future directions for G-CSF use are also discussed. Keywords Granulocyte colony-stimulating factors . Febrile neutropenia . Cytotoxic chemotherapy . Myelosuppression . Filgrastim . Pegfilgrastim
Introduction Myelosuppression represents the main dose-limiting toxicity associated with systemic cancer chemotherapy. Febrile neutropenia (FN) remains a major threat to patients treated with S. Cortés de Miguel (*) : M. Á. Calleja-Hernández : I. Vallejo-Rodríguez Pharmacy Service, UGC Intercentro-Interniveles, University Hospital Virgen de Las Nieves, Av de las Fuerzas Armadas, 2, 18014 Granada, Spain e-mail: [email protected] S. Menjón-Beltrán Department of Gynecology and Obstetrics, University Hospital Virgen de las Nieves, Granada, Spain
chemotherapy, resulting in impaired quality of life, increased risk of infections, and even death [1–4]. Chemotherapyinduced FN may also result in dose delays and reductions, which may compromise treatment effectiveness and worsen patient outcomes [5, 6]. This may impact on the success of treatment, particularly when treatment intent is either curative or to prolong survival [7]. The role of neutropenia in increasing the risk of serious infection in patients with cancer receiving cytotoxic chemotherapy was first recognized in the mid-1960s. In a study with patients whose absolute neutrophil count (ANC) remained below 1.0×109/L for 7 days, the probability of developing an infection was more than 50 %, and the risk of infection approached 100 % with longer duration of severe neutropenia [8]. This risk can be modified by alterations of physical defense barriers (oral mucositis or the presence of indwelling intravenous catheters), the status of the patient’s cellular and humoral immune system, and the patient’s endogenous microflora or organisms acquired in the hospital, clinic, or community [9]. The administration of chemotherapy can not only decrease the number of neutrophils but also produce chemotactic and phagocytic defects. The ANC is generally used to classify the severity of neutropenia as follows [10]: grade 1: ANC
