METHODS
Between November 2016 and June 2019, a retrospective analysis of the patients who used pegfilgrastim
with solid malignancies treated in the University of Health Sciences, Dr. A. Y. Ankara Oncology Hospital
Department of Medical Oncology was performed.
RESULTS
A total of 148 patients were evaluated, and 33 (22.2%) of them were in the geriatric population (age>65).
The majority of the patients (n=97, 65.5%) were diagnosed with breast carcinoma, and 93.2% (n=138)
of all patients were treated with the intermediate-risk chemotherapy regimen. Pegfilgrastim was used
as secondary prophylaxis for all of the patients. Despite pegfilgrastim prophylaxis, febrile neutropenia
(FN) developed in four (2.7%) patients. Chemotherapy delay due to afebrile neutropenia occurred in
eight patients (5.4%), and neutrophil counts returned to normal in mean 4.0 (3-5) days. When side effects
were evaluated, 31 patients (20.9%) had pegfilgrastim-induced bone pain and two patients (1.3%)
had redness in the injection site.
CONCLUSION
The low incidence of FN and chemotherapy delay, even in secondary prophylaxis with pegfilgrastim,
suggests that pegfilgrastim is an effective agent in neutropenia prophylaxis.
Keywords: Febrile neutropenia; granulocyte colony-stimulating factors; pegfilgrastim
The use of G-CSF significantly reduces the rates of
neutropenia and the presence of FN due to chemotherapy.
Filgrastim is a widely-used recombinant human G-CSF, which lasts longer than 25 years in the treatment
of neutropenia. Pegfilgrastim is a new generation
G-CSF with different pharmacokinetic properties.
[
In this report, we aimed to evaluate the results of
the use of pegfilgrastim as secondary prophylaxis in
patients who were diagnosed with solid malignancy
and treated in our center.
Patients with solid malignancy, >18 years old and who used pegfilgrastim at least once for FN prophylaxis were included in this study. Patients with hematologic malignancies were excluded from this study. Due to the regulations in our country, all patients who received pegfilgrastim had a neutrophil count <500 or FN at least once after previous chemotherapy cycles.
Patients" demographic characteristics, comorbidity, Eastern Cooperative Oncology Group (ECOG) performance score, type and stage of the malignancy, chemotherapy regimen, previous radiotherapy, number of cycles the pegfilgrastim applied, chemotherapy delayed due to neutropenia, history of FN, hospitalization due to FN, duration of grade 4 neutropenia and pegfilgrastim related side effects were recorded.
Chemotherapy regimens were grouped according to the guidelines of the National Comprehensive Cancer Network (NCCN) 2.2018 for the risk of FN.
Neutropenia was defined as an absolute neutrophil count of <1500 mcL. The fever ( ≥38.3°C or 38.0°C over 1 hour) with grade 4 neutropenia (neutrophil <500 mcL) was accepted as FN.
Descriptive statistics were performed using the SPSS 23 statistical program.
The most commonly used chemotherapy regimen was the combination of doxorubicin and cyclophosphamide (n=81, 54.7%). According to the risk of FN of the given chemotherapies, 10 patients (6.7%) had high-risk chemotherapy, and the other patients received intermediate-risk chemotherapy. In our study, there was no patient who received neoadjuvant chemotherapy or used pegfilgrastim simultaneously with radiotherapy.
A single dose of 6 mg pegfilgrastim was administered subcutaneously 24 hours after chemotherapy, during median 3 (1-12), a totally of 425 chemotherapy cycles.
Despite pegfilgrastim prophylaxis, FN developed in four (2.7%) patients. One patient was over 65 years of age, and the other patient had high-risk chemotherapy. All of these patients were hospitalized, and the mean duration of grade 4 neutropenia was two (1-3) days. No additional dose of G-CSF (filgrastim, lenograstim) was applied to patients after the development of FN.
One patient with metastatic breast carcinoma who had previously undergone multiple-line chemotherapy was died due to sepsis. This patient was being treated with eribulin at the sixth line for metastatic breast cancer. Before the third cycle of eribulin mesylate administration, the patient"s ECOG performance score was 1, white blood cell (WBC) and neutrophil was 7500 mL/3500 mL, respectively. Although pegfilgrastim was administered 24 hours after chemotherapy, septic shock developed after 10 days.
Chemotherapy delay due to afebrile neutropenia occurred in eight patients (5.4%), and neutrophil counts returned to normal in mean 4.0 (3.0-5.0) days.
When the side effects were evaluated, pegfilgrastiminduced bone pain was present in 31 patients (20.9%), and redness in the injection site was 2 (1.3%). Median 18.3 (3.5-30.5) months follow-up, no secondary malignancy occurred. There was no patient whose pegfilgrastim prophylaxis was stopped due to side effects.
In this study, despite the pegfilgrastim prophylaxis,
the incidence of development of FN was 2.7%. In
phase 3, randomized trial, which compared pegfilgrastim with filgrastim in patients with breast carcinoma,
the incidence of FN was seen 13% in the pegfilgrastim
arm after combination chemotherapy of docetaxel
and doxorubicin.[
A lower incidence of FN has been reported in patients
receiving intermediate-risk chemotherapy with
pegfilgrastim prophylaxis. In patients with colorectal
cancer, the efficacy of pegfilgrastim after the 5-fluorouracil,
leucovorin and oxaliplatin combination
(FOLFOX)/5-fluorouracil, leucovorin and irinotecan
combination (FOLFIRI) regimen was evaluated, and
the FN rate was found 3.2%.[
In Vogel et al."s study, the rate of hospitalization
due to FN was reported as 1% in the pegfilgrastim arm.
[
In our study, the mean duration of grade 4 neutropenia
was two (1-3) days. Similar to our study,
Holmes et al. reported that the mean duration of grade
4 neutropenia for the patients who developed FN was
1.7 days.[
In the previous studies, it was reported that the frequency
of bone pain due to pegfilgrastim was 18-37%.
[
One of the limitations of this study was the heterogeneous
group of patients concerning oncologic diagnoses
and chemotherapy regimens. The other limitation
was the retrospective feature of our study.
Although all the patients in our study consisted
of patients who had previously developed grade 4
neutropenia, it was observed that there was a low incidence
of FN and chemotherapy delay in secondary
prophylaxis with pegfilgrastim.
Peer-review: Externally peer-reviewed.
Conflict of Interest: The authors have no conflicts of interest to declare.
Ethics Committee Approval: The authors declare that this research was conducted according to the principles of the World Medical Association Declaration of Helsinki "Ethical Principles for Medical Research Involving Human Subjects" (amended in October 2013).
Financial Support: The authors declare that this study received no financial support.
Authorship contributions: Concept - F.Y., U.D., B.Ö.; Design - F.Y., U.D.; Supervision - B.Ö., U.D.; Funding - None; Materials - F.Y., A.İ., F.A.; Data collection and/or processing - F.Y., A.İ.; Data analysis and/or interpretation - F.Y., E.E., F.A.; Literature search - F.Y., G.T.; Writing - F.Y., G.T., E.E.; Critical review - F.Y., B.Ö., U.D.
