A prospective study to evaluate febrile neutropenia incidence in patients receiving pegfilgrastim on-body injector vs other choices.

PURPOSE: We evaluated the incidence of febrile neutropenia (FN) and related clinical outcomes among patients treated with myelosuppressive chemotherapy for nonmyeloid malignancies who received pegfilgrastim on-body injector (OBI) or other options (Other) for FN prophylaxis. METHODS: In this prospective observational study, adult patients with breast, prostate, or lung cancer, or non-Hodgkin lymphoma at risk for FN were stratified into subgroups based on FN prophylaxis used in the first chemotherapy cycle: pegfilgrastim OBI vs Other (pegfilgrastim or biosimilar pegfilgrastim prefilled syringe, daily filgrastim, or no granulocyte colony-stimulating factor [G-CSF]) for up to 4 planned chemotherapy cycles. RESULTS: This US study enrolled 2575 eligible patients (OBI, 1624; Other, 951). FN incidence was lower in the OBI group (6.4% [95% CI, 5.2-7.6%]) than in the Other group (9.4% [7.5-11.2%]), with a relative risk (RR) of 0.66 (0.47-0.91; p = .006). A decreased risk of dose delays among patients receiving pegfilgrastim OBI vs Other was observed (RR for ≥ 5 days: 0.64 [0.42-0.96], p = .023; RR for ≥ 7 days: 0.62 [0.40-0.91], p = .016). Adherence, defined as G-CSF support for all chemotherapy cycles, was 94.0% (92.9-95.2%) in the OBI group compared with 58.4% (55.2-61.5%) in the Other group. Compliance with pegfilgrastim, defined as administration the day after chemotherapy, was 88.3% in the OBI group and 48.8% in the prefilled syringe group. CONCLUSION: Patients receiving pegfilgrastim OBI had a lower incidence of FN compared with those receiving alternatives. The OBI was associated with improved adherence to and compliance with clinically recommended G-CSF prophylaxis.

A retrospective evaluation of chemotherapy dose intensity and supportive care for early-stage breast cancer in a curative setting.

Early-stage breast cancer (ESBC) is commonly treated with myelosuppressive chemotherapy, and maintaining full-dose chemotherapy on the planned schedule is associated with improved patient outcome. Retrospective analysis of patients with ESBC treated from 1997 to 2000 showed that 56 % of patients received a relative dose intensity (RDI) <85 % (Lyman et al., J Clin Oncol 21(24):4524-4531, 2003). To determine current practice, we evaluated treatment patterns at 24 US community- and hospital-based oncology practices, 79 % of which participated in the previous study. Data were abstracted from medical records of 532 patients with surgically resected ESBC (stage I-IIIa) treated from 2007 to 2009, who were ≥18 years old and had completed ≥1 cycle of one of the following regimens: docetaxel + cyclophosphamide (TC); doxorubicin + cyclophosphamide (AC); AC followed by paclitaxel (AC-T); docetaxel + carboplatin + trastuzumab (TCH); or docetaxel + doxorubicin + cyclophosphamide (TAC). Endpoints included RDI, dose delays, dose reductions, grade 3/4 neutropenia, febrile neutropenia (FN), FN-related hospitalization, granulocyte colony-stimulating factor (G-CSF) use, and antimicrobial use. In this study, TC was the most common chemotherapy regimen (42 %), and taxane-based chemotherapy regimens were more common relative to the previously published results (89 vs <4 %). Overall, 83.8 % of patients received an RDI ≥85 %, an improvement over the previous study where 44.5 % received an RDI ≥85 %. Other changes seen between this and the previous study included a lower incidence of dose delays (16 vs 25 %) and dose reductions (21 vs 37 %) and increased use of primary prophylactic G-CSF (76 vs ~3 %). Here, 40 % of patients had grade 3/4 neutropenia, 3 % had FN, 2 % had an FN-related hospitalization, and 30 % received antimicrobial therapy; these measures were not available in the previously published results. Though RDI was higher here than in the previous study, 16.2 % of patients still received an RDI <85 %. Understanding factors that contribute to reduced RDI may further improve chemotherapy delivery, and ultimately, patient outcomes.

Cyclic and chronic neutropenia.

Patients with severe chronic neutropenia have blood neutrophil level <0.5 × 10(9)/L, predisposing them to increased susceptibility to life-threatening bacterial infections. This chapter focuses on cyclic and congenital neutropenia, two very interesting and rare hematological conditions causing severe chronic neutropenia. Both disorders respond well to treatment with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF). This chapter describes the basic features of these diseases and addresses several current clinical issues regarding their diagnosis and management. Cyclic neutropenia is a rare, inherited autosomal dominant disorder due to mutations in the gene for neutrophil elastase (ELA-2 or ELANE). Usually these patients have regular oscillation of blood neutrophil counts with periods of severe neutropenia occurring every 21 days. During these periods, they have painful mouth ulcers, fevers, and bacterial infections. The most severe consequences are gangrene, bacteremia, and septic shock. Cyclic neutropenia patients respond well to treatment with granulocyte colony-stimulating factor (G-CSF) given by subcutaneous injections on a daily or alternate-day basis. Severe congenital neutropenia is also a rare hematological disease, but it is probably more common than cyclic neutropenia. Blood neutrophils are extremely low on a continuing basis; the levels may be <0.2 × 10(9)/L, and the risk of severe bacterial infections is even greater than in cyclic neutropenia. The majority of cases are due to autosomal dominant inheritance of mutations in the ELA-2 or ELANE gene. Less commonly, mutations in HAX-1, G6PC3, and other genes cause this disorder. Treatment with G-CSF is usually effective, but the dose of G-CSF required to normalize blood neutrophils varies greatly. Ten to thirty percent of severe congenital neutropenia patients evolve to develop acute myeloid leukemia, necessitating careful clinical monitoring.

Cyclic neutropenia.

Cyclic neutropenia is a rare hematologic disorder, characterized by repetitive episodes of fever, mouth ulcers, and infections attributable to recurrent severe neutropenia. Fluctuations in blood cells are due to oscillatory production of cells by the bone marrow. Recent genetic, molecular, and cellular studies have shown that autosomal-dominant cyclic neutropenia and sporadic cases of this disease are due to a mutation in the gene for neutrophil elastase (ELA2), located at 19p13.3. This enzyme is synthesized in neutrophil precursors early in the process of primary granule formation. It is currently presumed that the mutant neutrophil elastase functions aberrantly within the cells to accelerate apoptosis of the precursors, resulting in effective and oscillatory production. Cyclic neutropenia is effectively treated with granulocyte colony-stimulating factor (G-CSF), usually at doses of 1 to 5 microg/kg/d (median dose, 2.5 microg/kg/d). Long-term, daily, or alternate-day administration reduces fever, mouth ulcers, and other inflammatory events associated with this disorder. Leukemic transformation is not a recognized risk for cyclic neutropenia, with or without treatment with G-CSF.

Optimizing the management of chemotherapy-induced neutropenia.

Chemotherapy-induced neutropenia (CIN), the most common dose-limiting toxicity of cancer chemotherapy, is associated with numerous clinical, personal, and economic consequences. The principal strategies for managing CIN are reducing the dose intensity of the chemotherapy, using antibiotics, and using colony-stimulating factors (CSFs). Reducing or delaying the chemotherapy dose is effective, but this can compromise treatment outcomes. Antibiotics can be lifesaving, but they are associated with numerous adverse effects and the emergence of resistant pathogens. The granulocyte CSF (G-CSF) filgrastim can reduce the incidence, duration, and severity of CIN, as well as the risk of infection, in patients treated with myelosuppressive chemotherapy. The availability of pegfilgrastim, a sustained-duration G-CSF that has benefits comparable to those of filgrastim with a single injection per chemotherapy cycle, has simplified CSF therapy.