• Korean Journal of Clinical Pharmacy
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• v.13 no.2
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• pp.59-66
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• 2003

Filgrastim is used as an indispensable adjuvant drug to reduce the degree and duration of chemotherapy-induced neutropenia. The purpose of this research is to study the use of filgrastim by reviewing retrospective medical records of breast cancer patients who have been treated by filgtastim in the National Cancer Center. 84 patients have received 323 cycles of chemotherapy, of which 134 cycles were treated by filgrastim $(41.5\%)$. Among those 134 cycles, 34 were for prophylaxis $(21.6\%)$, and 100 for treatment of neutropenia $(74.6\%)$. The frequence of filgrastim usage was more than $50\%$ in frequency with regimens containing docetaxel. For prophylaxis, the median of filgrastim initiation was measured on the day of chemotherapy (-3rd-13th). For the treatment, on the other hand, the median appeared on the 9th day (4th-2lst) after chemotherapy, which showed very wide distribution. Time to filgrastim initiation ranged between the 7th and the 9th day after chemotherapy in docetaxel+doxorubicin combination regimen and docetaxel single regimen, whereas it showed after the 10th day in doxorubicin+cyclophosphamide combination regimens. For the treatment, 48 out of 61 patients $(73.8\%)$ in 63 cycles have experienced fever, had to visit the emergency room, required hospitalization, caused infection, transfusion, dosage reduction and schedule changes in spite of using filgrastim with chemotherapy. For prophylaxis, 11 out of 19 patients $(17.9\%)$ in 11 cycles have experienced the same results. In conclusion, the guideline of time to the initiation and the last is required for cost-effective administration of filgrastim because of the difference occurring ANC nadir, the severity and duration of neutropenia by chemotherapy regimens.

• Korean Journal of Clinical Pharmacy
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• v.25 no.3
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• pp.151-158
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• 2015

Objective: This study was designed to compare pegfilgrastim and filgrastim in diffuse large B-cell lymphoma (DLBCL) patients treated with a rituximab with cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP) regimen in terms of clinical efficacy and cost-effectiveness. Method: Clinical efficacy was measured by trough level of absolute neutrophil count (ANC), days of ANC under 50% of baseline value, days of ANC under 90% of baseline value, duration of ANC recovery to baseline value, days of ANC less than $0.5{\times}10^9cells/L$, and difference of peak and trough level of ANC during 1 cycle of R-CHOP regimen. To evaluate cost-effectiveness, total prices of used filgrastim and pegfilgrastim within 1 cycle of R-CHOP were analyzed. Results: In terms of clinical efficacy, trough level of ANC and days to ANC recovery showed statistical significance. The median trough levels of ANC with administration of filgrastim and pegfilgrastim were 0.18 and 1.94 (p = 0.021), respectively, and the median durations of ANC recovery to baseline value were 5.5 days and 2 days (p = 0.023), respectively. For the median days of ANC under 50% of baseline value, days of ANC under 90% of baseline value, days of ANC less than $0.5{\times}10^9cells/L$, and difference of peak and trough level of ANC during 1 cycle of R-CHOP, the pegfilgrastim group performed better than the filgrastim group. However the difference was not statistically significant. In terms of overall expense during 1 cycle of R-CHOP, pegfilgrastim is about 3.43 times more expensive than filgrastim. Conclusion: Pegfilgrastim is more efficient than filgrastim in terms of clinical efficacy. In terms of prices, pegfilgrastim is more expensive than filgrastim for patients, but it is more convenient in clinical use. Therefore, pegfilgrastim should be the preferred choice of G-CSF for neutropenic patients. Further comparative study of pegfilgrastim and filgrastim is needed.

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.3
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• pp.17-23
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• 2009

Purpose: It has been known that PET/CT is very valuable in follow-up study of diffuse large B cell lymphoma (DLBCL). Generally, in DLBCL, radiotherapy and chemotherapy has been progressed, because the lesion hasn‘t been limited to one site. And, it has lead to the decrease of leukocyte like neutropenia, due to myelosuppression of chemotherapy. So, in that case, administration of Filgrastim (Granulocyte colony-stimulating factor; G-CSF) is universal. However, in short time after administration, PET/CT has limitation to offer accurate images, through the uptake of $^{18}F$-FDG is increased in the region that is activated bone marrow by hematopoietic growth. Therefore, the aim of this study is that PET/CT in a certain period of time after administration of Filgrastim is able to show normal degree of $^{18}F$-FDG uptake. Materials and Methods: 10 patients under follow-up study of diffuse large B cell lymphoma were examined in this study from January, 2007 to January, 2009 (Male: 4 persons; Female: 6 persons; The mean age: 53.8 years old; The mean weight: 57.3 Kg). Using PET/CT (Discovery STe; GE Healthcare, Milwaukee, WI, USA), whole body images were acquired in 1 hour after $^{18}F$-FDG injection. For image analysis, each ROI ($120\;mm^2$) was drawn on $C^6$ (the sixth C-spine), $L_4$ (the forth L-spine), liver, spleen, and lung, then SUV (Standard Uptake Value)s were measured. We compared with each uptake between in 1-day and 5~7 days after administration of Filgrastim at same patient, so confirmed significance about these by SPSS version 12. Results: In case of $C_6$, $L_4$, spleen, every SUV of 1 day later was remarkably higher than that of 5~7 days later, but liver and lung were similar. Also, the images acquired after 5~7 days distinct remarkably and show normal degree of $^{18}F$-FDG uptake, because uptake of bone was almost disappeared. Conclusions: In this study, each SUV was prominent difference as a period of time after Filgrastim’s administration. And Filgrastim makes concentrate uptake of $^{18}F$-FDG in bone, but, after 5~7 days, bone‘s uptake was greatly decreased. Therefore, we are able to infer a certain period of time that shows normal degree of uptake, by numerical value proven. Also, we consider that this study contribute to advanced study about the other agent like Pegfilgrastim, Lenograstim besides Filgrastim, afterwards.

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.89-94
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• 2001

The pharmacokinetics of recombinant human granulocyte colony stimulating factor (rhG-CSF) following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of HM1041l-lyo and HM10411-liq (lyophilized and liquid formulations of rhG-CSF, recently under development by Hanmi Pharmaceutical Company) were studied in rats, and compared with that of Filgrastim (conventional formulation of rhG-CSF on market). The plasma concentration of rhG-CSF was quantified using a specific ELISA. The pharmacokinetic parameters of rhG-CSF, after i.v., i.m. and s.c. administration of Filgrastim, HM1041l-lyo and HM1041l-liq to rats at a rhG-CSF dose of $10\;{\mu}g/kg$, were almost identical among the three formulations. No dose-dependency was observed in the pharmacokinetic parameters of rhG-CSF following i.v. administration in the dose range of $5{\sim}100\;{\mu}g/kg$. rhG-CSF, after i.v. administration of the three preparations at a dose of $10\;{\mu}g/kg$ to rats, was detected at low levels in all of the body tissues with highest tissue/plasma ratio of $0.46{\sim}0.51$ for the kidney at 30 min after the administration. The pharmacokinetics of rhG-CSF, after i.v. administration to mice at a dose of $10\;{\mu}g/kg$, were comparable among the three formulations. In conclusion, HM10411-lyo and HM10411-liq exhibited similar pharmacokinetics for rhG-CSF with Filgrastim regandless of animal species. Considering the fact that HM10411 series, contrary to Filgrastim, are proteins lacking a methionine residue, the methionine moiety in rhG-CSF molecule does not appear to influence the pharmacokinetics of the protein significantly.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.561-565
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• 2005

Bronchiolitis obliterans organizing pneumonia (BOOP) is often diagnosed in patients with pneumonia who respond poorly to antibiotics. BOOP is often idiopathic, and the etiology of the remaining cases has been attributed to a wide range of agents or medical conditions. When a patient develops the clinical symptoms characteristic of BOOP, the medical team must endeavor to determine the etiology of this disease because it can be treated with glucocorticoid and avoidance of the causative agent. In particular, if BOOP is diagnosed during or after chemotherapy for a malignancy, the possible culprit agent can be the anti cancer drugs but other drugs used for supportive care must be also be considered. We report a case of BOOP that arose after CHOP chemotherapy and a filgrastim injection in a patient with a diffuse large B-cell lymphoma.

• Toxicological Research
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• v.17 no.2
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• pp.151-157
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• 2001

Neutropenia is a major dose-limiting side effect of cancer chemotherapy. The therapeutic effect of HM 10411 was examined on neutropenia caused by anticancer agents. Neutropenia in normal ICR mice was induced by a single combined intraperitoneal injection of 130 mg/kg of cyclophosphamide (CPA). 4.5 mg/kg of doxorubicin (DXR). and 1 mg/kg of vincristine (VCR) on day O. Neutropenia in tumor-bearing mice was made by a single intraperitoneal injection of 200 mg/kg of cyclophosphamide (CPA) into BALB/c mice bearing Colon 26 adenocarcinoma at 7 day after tumor implantation. HM 10411 or filgrastim (100 $\mu\textrm{g}$/kg/day) was subcutaneously administered for 5 consecutive days starting 1 day after injection of anticancer agents in order to stimulate neutrophil production. Injection of HM 10411 accelerated the recovery from these anticancer drug-induced neutropenia. In normal and tumor-bearing mice. neutrophil production efficacy of HM 10411 was similar than that of filgrastim. These results suggest that HM 10411 could be useful in the clinical treatment for neutropenia induced by anticancer agents.

• Journal of Life Science
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• v.21 no.11
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• pp.1652-1657
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• 2011

The production of blood cells is regulated by more than 20 different growth factors, called hematopoitic growth factors. These factors have been produced in prokaryotic and mammalian systems for their clinical use. Glranulocyte-Colony Stimulating Factor (G-CSF) is an important therapeutic factor for cancer patients as well as patients with congenital conditions. These patients do not have enough neutrophils and have a high risk of infection. Two groups of recombinant G-CSF have been used to specially treat cancer patients after chemotherapy because chemotherapy induces neutropenia, a major side effect of chemotherapy drugs. Here, structural and biological characteristics of G-CSF are presented. In addition, the relationship between chemotherapy and neutropenia, which is a severe reduction of neutrophils in the blood, and clinical application of G-CSF is discussed. Recombinant G-CSFs are grouped in two forms. Non-glycosylated G-CSF, filgrastim, is produced in Escherichia coli and glycosylated G-CSF, lenograstim, is produced in Chinese hamster ovary cells. Differences in structure and biological activity are compared and challenges for biosimilar production are also highlighted.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1185-1189
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• 2015

Background: Chemotherapy-induced febrile neutropenia (FN) with solid tumors causes mortality and morbidity at a significant rate. The purpose of this study was to compare the effects of filgastrim and lenograstim started with the first dose of antibiotics in hospitalized patients diagnosed with FN. Materials and Methods: Between February 2009 and May 2012, 151 patients diagnosed with FN were evaluated, retrospectively. In those considered appropriate for hospitalization, convenient antibiotic therapy with granulocyte colony stimulating factors was started within first 30 minutes by completing necessary examinations in accordance with FEN guide recommendations. Results: In this study, 175 febrile neutropenia attacks in 151 patients were examined. Seventy three of the patients were male and 78 were female. The average age was 53.6 and 53.6, respectively. The most common solid tumor was breast carcinoma in 38 (25%). One hundred and five FN patients (58%) were those who received granulocyte colony stimulating factors as primary prophylaxis. Conclusions: While studies comparing both drugs generally involve treatments started for prophylaxis, this study compared the treatment given during the febrile neutropenia attack. Compared to lenograstim, filgastrim shortens the duration of hospitalization during febrile neutropenia attack by facilitating faster recovery with solid tumors.

• Clinical and Experimental Pediatrics
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• v.52 no.6
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• pp.633-642
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• 2009

Neutropenia is defined as an absolute neutrophil count (ANC) of <$1,500/{\mu}L$, and the severity of neutropenia generally can be graded as mild ($1,000-1,500/{\mu}L$), moderate ($500-1,000/{\mu}L$), or severe (<500/$\mu{L}$). This stratification aids in predicting the risk of pyogenic infection because the susceptibility to life-threatening infections is significantly increased in patients with prolonged episodes of severe neutropenia. Especially cancer-related neutropenia carry significant mortality. Neutropenia can develop under various conditions such as decreased bone marrow production, the sequestering of neutrophils, and increased destruction of neutrophils in the peripheral blood. Neutropenia is classified according to the etiology as congenital or acquired, with the latter further defined according to the etiology or pathology. The clinical result is increased risk for infection, which is directly proportional to the severity and duration of the neutropenia. The typical workup of neutropenia starts with a 6-week period in which complete blood counts are measured twice weekly to document the persistence of the neutropenia and whether a cyclic pattern is present. When persistent neutropenia is diagnosed and no spontaneous recovery occurs within 3 months, a more extensive evaluation is advised. Treatment is usually unnecessary for most patients with severe neutropenia, as the majority of patients have a good prognosis. However, for patients who have severe and frequent infections, treatment with filgrastim may prevent infectious complications and improve quality of life.

• Asian Oncology Nursing
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• v.8 no.1
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• pp.1-7
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• 2008

Purpose: Peripheral blood stem cell transplantation (PBSCT) has been widely used. The optimal time for collection is a critical factor to obtain proper counts of CD34 cell by peripheral blood stem cell collection (PBSC). The purpose of this study was to identify the factors influencing peripheral blood stem cell collection in order to figure out the more effective timing for PBSC. Method: The subjects of this study were 189 patients undergoing 3 leukapheresis from January 28, 2005 to December 31,2006. Group's characteristics, checkup opinion of pre-peripheral blood on the day of harvest & outcome of PBSC were analyzed and evaluated using SAS statistics program after grouping patients as below; group 1-CD34 cell counts $<2{\times}10^6/kg$ (n=97); group $2-2{\times}10^6/kg$ ${\leq}CD34$ cell counts $<4{\times}10^6/kg$ (n=26); group 3-CD34 cell counts ${\geq}4{\times}10^6/kg$ (n=63). Results: Based on outcome of peripheral blood stem cell according to diagnosis, acute myelocytic leukemia (AML) was 65.5% at Group 1, Lymphoma was 21.7% at Group 2 and multiple myeloma (MM) was 70.8% at Group 3. There were significant differences in CD34 cell counts according to diagnosis (p=0.00004). Type of cytokine mobilization according to diagnosis, Lenograsim was using 62.5% of MM & 38.2% of AML and filgrastim is using 22.0% of AML only. Circular peripheral blood CD34 cell counts prior to harvest was $258.1/{\mu}L$ at Group 3 which was much higher comparing to Group 1 ($10.5/{\mu}L$) and Group 2 ($39.9/{\mu}L$) (p<0.001). TNC counts of collected peripheral blood stem cell was $15.36{\times}10^6/kg$ at Group 3 and it's much higher than Group 2 ($13.16{\times}10^6/kg$) and Group 1 ($12.36{\times}10^6/kg$) (p=0.083). There was no significant difference in MNC counts inbetween 3 groups. Conclusions: Circular peripheral blood CD34+ cell counts prior to harvest was much higher at Group 3 than Group 1 and Group 2. Therefore, the number of CD34+ cells on the day of harvest can be used as an accurate predictor for peripheral blood stem cell.