Prevention of Febrile Neutropenia Even More Important in Elderly Cancer Patients

A primary indication for the granulocyte colony-stimulating factors (GCSFs) like filgrastim and pegfilgrastim is to prevent the incidence of cancer chemotherapy–induced febrile neutropenia, a serious complication of toxic oncologic treatments. Elderly patients are at higher risk for febrile neutropenia.

One less-frequently discussed issue associated with the use of GCSF treatment is the possibility for under- and over-prophylaxis. Apparently, under current protocols, it is not so simple to ensure that a patient with cancer who is at risk for neutropenia is receiving the right dose or duration of GCSF therapy, or initiated at the appropriate time. In a previous European study zarxio(https://www.ncbi.nlm.nih.gov/pubmed/26306517), 17% of patients were found to be undertreated with filgrastim and 26% of patients were overtreated, meaning just 57% of patients taking this therapy were receiving appropriate prophylaxis. A study evaluating European experience with Sandoz’s and Hexal AG’s biosimilar filgrastim (marketed today as Zarzio® in the EU, Zarxio® in the US) focused specifically on whether elderly patients with cancer were given correct prophylaxis.

The MONITOR-GCSF study involved patients from 12 European countries. This most recent analysis (http://dx.doi.org/10.1016/j.jgo.2016.09.006) stratified patients by age (< 65 yr and ≥ 65 yr). A total of 598 patients (41%) were in the older age group. Patients were considered eligible if they had mid- to late-stage breast, ovarian, bladder, or lung cancer; prostate cancer; diffuse large B-cell lymphoma, or multiple myeloma. The researchers assessed when patients began filgrastim therapy (covering up to 6 cycles of chemotherapy), its appropriateness based on EORTC protocols, and its relationship to the primary outcomes: grade 4 chemotherapy-induced febrile neutropenia or any febrile neutropenia episodes, and the need for hospitalization as a result.

In the evaluable patient population, 95% were prescribed the standard dose of chemotherapy appropriate to their tumor diagnosis. However, the study did not report the percentage of patients who completed the intended number of cycles. Similar proportions of patients were receiving primary or secondary prophylaxis in each group (e.g., primary prophylaxis, 70% in the older group, 74% in the younger group). The researchers determined that elderly patients were more likely to be under-prophylacted (26% of the elderly patients, 11% of younger patients) and less likely to be over-prophylacted (11% vs. 37%, respectively). Sixty-three percent and 52%, respectively, were considered to have received correct prophylaxis. The most common independent predictors of poor neutropenia outcomes were the use of antibiotic prophylaxis, lower performance status scores, and the occurrence of chemotherapy-induced neutropenia (any grade) in a previous cycle of therapy.

The researchers acknowledge that age 65 may not be the best definition of “elderly patients” in the current environment, but they did not assess subgroups of older patients (i.e., > 70 or > 75 yr). Interestingly, one of the determinants of positive outcomes was the incidence of over-prophylaxis. The authors suggest that prospective randomized studies should be undertaken to consider the implications of this finding. For elderly patients specifically, the presence of cardiovascular or liver disease, secondary prophylaxis, and under-prophylaxis were linked with poor neutropenia outcomes.

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