• Toxicological Research
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• v.31 no.4
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• pp.371-392
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• 2015

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

• 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.

• 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.

• 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.