• 한국임상약학회지
• /
• 제13권2호
• /
• pp.59-66
• /
• 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.

• 한국임상약학회지
• /
• 제25권3호
• /
• pp.151-158
• /
• 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.

• 핵의학기술
• /
• 제13권3호
• /
• pp.17-23
• /
• 2009

많은 암 환자들 중 특히 미만성 거대 B 세포 림프종 환자의 추적 검사에서 PET/CT 검사는 기타 다른 검사들과 견주어 볼 때 매우 중요하다는 것은 이미 알려져 있다. 이들 환자의 치료는 대부분 환자의 장기 한 곳에 국한된 경우가 없으므로, 방사선 치료나 항암 화학 요법 치료로 시행한다. 이러한 항암 화학 요법 치료는 골수의 활동을 억제하는 치료이기 때문에 환자에게서 호중구감소증과 같은 백혈구의 감소가 나타날 수 있다. 이러한 증상을 개선하기 위하여 과립구 자극요소(Granulocyte colony-stimulating factor)인 Filgrastim 성분의 골수촉진제를 사용하는 경우가 일반적이며, 이 약제가 투여된 환자에게서 단기간에 PET/CT 검사를 진행하게 되면, 검사에 사용되는 $^{18}F$-FDG의 섭취가 조혈 세포가 모여 있는 골수의 활성화로 그 곳에 섭취가 가중되어 정확한 영상의 정보를 얻는데 한계가 있다. 이 연구의 목적은 Filgrastim의 약제 투여 1일 후의 영상과 어느 정도 시간이 지난 후 영상의 SUV를 각각 비교하여 수치화하고, 대략 어느 정도 시간이 지난후에 정확한 영상의 정보를 줄 수 있는 $^{18}F$-FDG의 섭취가 일어나는지를 유추해 보고자 한다. 환자대상은 2007년 1월~2009년 1월까지 미만성 거대 B 세포 림프종을 진단받고 추적 검사 중인 환자 10명을 대상으로 하였다. 남자 4명, 여자 6명이고, 평균나이는 53.8세 평균 체중은 57.3 kg이다. PET/CT (Discovery STe; GE Healthcare, Milwaukee, WI, USA) 검사를 위해 환자에게 $^{18}F$-FDG 정맥주사 후 1시간 가량 안정시키고, PET/CT 영상을 획득하였다. 영상 분석은 ROI ($12\;mm^2$)를 $C_6$ (6 번 경추), $L_4$ (4 번 요추), 간, 비장, 폐에 각각 그린 후 표준화 섭취 계수(SUV)를 측정하였다. 같은 환자를 골수촉진제 주사 1일 후 영상과 5~7일 후 영상을 각각 분석하였으며, 통계 프로그램으로는 SPSS version 12. Wilcoxon signed rank test를 사용하여 두 집단 간의 유의성을 확인하였다. 검사를 시행한 10명의 환자의 SUV를 분석한 결과, 골수촉진제를 투여하고 1일 후의 SUV가 5~7일 후에 비해 $C_6$ (6 번경추), L4 (4 번 요추), 비장에서 현저하게 높게 나타났고, 간과 폐에서는 비슷하게 나타났다. SUV의 차이와 더불어, 5~7일 후의 영상에서는 뼈의 섭취가 거의 없어진 정상 섭취 영상을 얻을 수 있었다. 위의 연구에서도 보여진 것과 같이 과립구 자극요소 약제투여 후 1일째 환자의 영상과 5~7일 후의 영상에서 SUV의 현저한 차이가 있었으며, 약제를 투여한 환자의 영상에 뼈의 $^{18}F$-FDG 섭취가 집중되었으며, 평균 5~7일 후에 검사에서는 뼈의 섭취가 현저하게 줄어든 정상적이 영상을 얻을 수 있었다. 본 연구를 통하여 SUV를 측정하고, 통계분석 함으로서 기존의 사실을 수치화 하였으며, 정상 섭취가 가능한 기간을 유추 할 수 있었다. 추후에 과립구 자극요소인 Filgrastim 이 외에 Pegfilgrastim, Lenograstim등 기타약제와의 유사성과 차이점에 대한 유사 연구에도 기여할 수 있으리라 사료된다.

• Journal of Pharmaceutical Investigation
• /
• 제31권2호
• /
• pp.89-94
• /
• 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
• /
• 제59권5호
• /
• pp.561-565
• /
• 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
• /
• 제17권2호
• /
• pp.151-157
• /
• 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.

• 생명과학회지
• /
• 제21권11호
• /
• pp.1652-1657
• /
• 2011

혈액세포의 분화와 성장은 20 여종 이상의 성장인자에 의해 조절된다. 혈액세포 생산에 관여하는 인자를 조혈 성장인자(hematopoitic growth factor)라고 한다. 조혈성장인자를 임상적으로 사용하기 위해 원핵생물 또는 진핵 생물 생산 시스템에서 재조합 단백질로 생산되고 있다. 그 중에서 Glranulocyte-Colony Stimulating Factor(G-CSF)는 호중구 세포 수가 감소된 암환자와 선천성 질병을 가진 환자에게 임상적 치료제로 아주 중요한 역할을 한다. 이 환자들은 충분하지 못한 호중구 세포로 말미암아 감염에 대한 위험이 아주 높으며 치사율 또한 높다. 두 종류의 재조합 G-CSF가 항암치료 후 발생하는 부작용으로 나타나는 호중구 세포 감소증 치료에 사용되고 있다. G-CSF의 중요성에 맞추어 G-CSF의 물리적 및 생물학적 기능에 대한 특성을 설명하였으며, 또한 항암치료와 G-CSF의 임상적 사용에 대한 연관성을 토론하였다. 마지막으로 두 종류의 재조합 G-CSF인 non-glycosylated G-CSF, filgrastim과 glycosylated G-CSF를 비교 설명하였으며, 이들 기존의 G-CSF에 비교되는 바이오시밀러에 대한 전망을 제시하였다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권3호
• /
• pp.1185-1189
• /
• 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
• /
• 제52권6호
• /
• pp.633-642
• /
• 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.

• 종양간호연구
• /
• 제8권1호
• /
• pp.1-7
• /
• 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.