• Korean Journal of Head & Neck Oncology
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• v.31 no.2
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• pp.21-28
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• 2015

서론: 국소 진행성 두경부암 환자에서 선행 항암요법 후 동시 항암화학방사선요법은 원격 전이를 줄이고, 국소병변을 줄여 방사선 치료의 효과를 높이거나, 기관의 기능을 보존할 목적으로 시도된다. 선행 항암요법의 약제로 는 docetaxel, cisplatin, fluorouracil (DPF) 삼제요법이 가장 효과적인 것으로 알려져 있다. 선행 항암요법 후 동시 항암화학방사선요법과 표준치료인 동시화학방사선요법을 비교한 3상 연구들이 모두 선행 항암요법이 더 낫다는 결과를 보여 주지 못하였지만, 이 연구들은 충분한 환자를 모집하지 못하고 조기 종료된 불완전한 연구라는 한계가 있었다. 이에 저자들은 DPF 선행 항암요법 후 동시 화학방사선요법과 표준치료인 동시 화학방사선요법을 비교하는 메타분석을 시행하였다. 대상 및 방법: 체계적 문헌고찰을 통해 국소진행성 두경부암 환자를 대상으로 시행된 DPF 선행 항암요법 후 동시화학방사선요법과 현재 표준치료인 동시화학방사선요법을 비교한 5개의 3상 연구 결과를 분석하였다. 대상환자는 862 명이었고, 분석 결과 DPF 선행 항암요법 후 동시화학방사선요법은 표준치료와 비교하였을 때 반응률, 2년 및 3년 생존율, 2년 및 3년 무진행 생존율, 점막염 및 빈혈 발생 빈도에서 통계적으로 유의한 차이가 없었다. 하지만, 완전관해율과 3~4도의 백혈구감소증 및 혈소판 감소증의 빈도는 선행 항암요법 시행군에서 더 높았다. 결론: 국소진행성 두경부암의 치료에서 DPF 선행 항암요법 후 동시 항암화학방사선요법을 시행하는 것은 표준치료인 항암화학방사선요법에 비해 생존율 개선을 보이지 못하였다. 선행항암치료를 추가하는 것이 특정 환자군에서 효과가 있을지에 대해서는 추가적인 연구가 필요하다.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9939-9943
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• 2014

Lobaplatin, one of the third - generation platinum compounds, has shown encouraging anticancer activity in a variety of tumor types. However, the efficacy of lobaplatin in ovarian cancer has not been systemically evaluated. In this study, lobaplatin as a single agent and in combination with taxanes was investigated in - vitro and in an in vitro model of ovarian carcinoma. Using the sulforhodamine B (SRB) assay, the cytotoxic effects of lobaplatin alone and in combination with taxanes were compared with cisplatin and carboplatin in seven ovarian cancer cell lines. In addition, in - vitro antitumor activities were evaluated with cisplatin - sensitive and cisplatin - resistant human ovarian cancer xenografts in nude mice. The cytotoxicity of lobaplatin was similar to or higher than that of cisplatin and carboplatin, with $IC_{50}$ values from 0.9 to $13.8{\mu}mol/L$ in a variety of ovarian cancer cells. The combination of lobaplatin with docetaxel yielded enhanced cytotoxic activity in vitro. In addition, in platinum - sensitive ovarian cancer xenografts, lobaplatin alone showed similar antitumor activity to cisplatin and carboplatin. Furthermore, lobaplatin alone or in combination with docetaxel exhibited significant activity in platinum - resistant ovarian cancer xenografts. These results indicate that the use of lobaplatin alone or in combination with docetaxel might be a rational and novel therapeutic strategy for ovarian cancer. Further clinical development of lobaplatin is clearly warranted.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6351-6356
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• 2013

Background: Goshajinkigan (GJG) is used for the treatment of several neurological symptoms. We investigated the efficacy of GJG and mecobalamin (B12) against neurotoxicity associated with docetaxel (DOC) in breast cancer patients. Materials and Methods: Sixty breast cancer patients were treated with DOC. Thirty-three patients (GJG group) received oral administration of 7.5 g/day GJG and 27 patients (B12 group) received oral administration of 1500 ${\mu}g/day$ B12. Neuropathy was evaluated according to DEB-NTC (Neurotoxicity Criteria of Debiopharm), Common Terminology Criteria for Adverse Events (NCI-CTC) ver. 3.0, and a visual analogue scale (VAS). This study employed a randomized open design. Results: The incidence of neuropathy was 39.3% in the GJG group, and 88.9% in the B12 group (p<0.01). In the GJG group, grade 1 DEB-NTC was observed in 2 cases, grade 2 in 5 cases and grade 3 in 5 cases. Grade 1 NCI-CTC was observed in 7 cases, grade 2 in 6 cases, and VAS was $2.7{\pm}2.2$. In the B12 group, grades 1, 2 and 3 DEB-NTC were observed in one case, 12 cases and 12 cases, respectively; and grades 1, 2 and 3 NCI-CTC were observed in 11 cases, 12 cases and one case, and VAS was $4.9{\pm}2.4$. Conclusions: Concomitant administration of GJG is useful in preventing neuropathy in breast cancer patients treated with a DOC regimen.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3471-3476
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• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Journal of radiological science and technology
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• v.38 no.4
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• pp.463-475
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• 2015

The standard treatment of locally advanced type of mid-esophageal cancer is concurrent chemoradiation therapy (CRT). We evaluated the feasibility of chemotherapy with adding docetaxel to the classical basic regimens of cisplatin plus 5-fluorouracil (5-FU) and radiotherapy up to 70.2 Gy using dose escalations for esophageal cancer. It was possible to escalate radiation treatment dose up to 70.2 Gy by the respiratory-gated intensity-modulated radiotherapy (gated-IMRT) based on the 4DCT-simulation, with improving target coverage and normal tissue (ex., lung, heart, and spinal cord) sparing. This study suggested that the definitive chemo-radiotherapy with docetaxel, cisplatin, and 5-fluorouracil (i.e., DCF-R) and gating IMRT is tolerable and active in patients with locally advanced mid-esophageal cancer (AEC).

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.479-488
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• 2021

This study aimed to develop docetaxel (DTX) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (DTX-NPs) and to evaluate the different pharmacological sensitivity of NPs to MCF-7 and MDA-MB-231 breast cancer cells. NPs containing DTX or coumarin-6 were prepared by the nanoprecipitation method using PLGA as a polymer and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a surfactant. The physicochemical properties of NPs were characterized. In vitro anticancer effect and cellular uptake were evaluated in breast cancer cells. The particle size and zeta potential of the DTX-NPs were 160.5 ± 3.0 nm and -26.7 ± 0.46 mV, respectively. The encapsulation efficiency and drug loading were 81.3 ± 1.85% and 10.6 ± 0.24%, respectively. The in vitro release of DTX from the DTX-NPs was sustained at pH 7.4 containing 0.5% Tween 80. The viability of MDA-MB-231 and MCF-7 cells with DTX-NPs was 37.5 ± 0.5% and 30.3 ± 1.13%, respectively. The IC₅₀ values of DTX-NPs were 3.92- and 6.75-fold lower than that of DTX for MDA-MB-231 cells and MCF-7 cells, respectively. The cellular uptake of coumarin-6-loaded PLGA-NPs in MCF-7 cells was significantly higher than that in MDA-MB-231 cells. The pharmacological sensitivity in breast cancer cells was higher on MCF-7 cells than on MDA-MB-231 cells. In conclusion, we successfully developed DTX-NPs that showed a great potential for the controlled release of DTX. DTX-NPs are an effective formulation for improving anticancer effect in breast cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.423-427
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• 2013

Background: Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but with high rates of hematologic toxicity in metastatic gastric cancer cases. To reduce toxicity while maintaining the efficacy of DCF, we investigated low dose docetaxel (D), cispatin (C) - leucovorin and fluorouracil (De Gramont regimen). Patient and methods: Chemotherapy-naïve patients with metastatic gastric cancer (MGC) received D 60 mg/$m^2$ on day 1 and cisplatin 30 mg/$m^2$ on day 1-2 and the De Gramont regimen (Folinic acid 400 mg/m2 on day 1 and 5-FU 2400 mg/$m^2$/46h continuous infusion) every 3 weeks. The primary endpoint was response rate. Results: One hundred twenty patients with a median age of 52.5 years (range, 32-78) received a median of 6 cycles (range, 2-12 cycles). Of the 120 evaluable patients, 4 showed complete remission and 36 achieved a partial response. The overall response rate was 56.6%. Twenty eight patients (23.3%) showed stable disease and 52 (43.3%) progression. The median time to progression was 7 months (95%CI 6-7.9). The median overall survival was 15 months (95%CI 13.7-16.2). The most frequent hematological toxicity was leucopenia, which occurred at grade 3/4 intensity in 24 patients (20%). Conclusions: Low-dose DC-De Gramont regimen is active in MGC with a tolerable toxicity profile.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.985-989
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• 2015

Background: Docetaxel, cisplatin, 5-fluorouracil (DCF) given every three weeks is an effective, but palliative regimen and significantly toxic especially in patients who have a low performance score. Here, we aimed to evaluate the efficacy and tolerability of a weekly formulation of DCF in locally advanced and metastatic gastric cancer patients. Materials and Methods: 64 gastric cancer patients (13 locally advanced and 51 metastatic) whose ECOG (Eastern Cooperative Oncology Group) performance status (PS) was 1-2 and who were treated with at least two cycles of weekly DCF protocol as first-line treatment were included retrospectively. The weekly DCF protocol included $25mg/m^2$ docetaxel, $25mg/m^2$ cisplatin, and 24 hours infusion of $750mg/m^2$ 5-fluorouracil, repeated every week. Disease and patient characteristics, prognostic factors, treatment response, grade 3-4 toxicity related to treatment, progression free survival (PFS) and overall survival (OS) were evaluated. Results: Of the patients, 41 were male and 23 were female; the median age was 63 (29-82) years. Forty-one patients were ECOG-1 and 23 were ECOG-2. Of the total, 81.2% received at least three cycles of chemotherapy. Partial response was observed in 28.1% and stabilization in 29.7%. Overall, the disease was controlled in 57.8% whereas progression was noted in 42.2%. The median time to progression was 4 months (95%CI, 2.8-5.2 months) and median overall survival was 12 months (95%CI, 9.2-14.8 months). The evaluation of patients for grade 3-4 toxicity revealed that 10.9% had anemia, 7.8% had thrombocytopenia and 10.9% had neutropenia. Non-hematologic toxicity included renal toxicity (7.8%) and thrombosis (1.6%). Conclusions: In patients with locally advanced or metastatic gastric cancer who were not candidates for DCF administered every-3-weeks, a weekly formulation of DCF demonstrated modest activity with minimal hematologic toxicity, suggesting that weekly DCF is a reasonable treatment option for such patients.

• Journal of the Korean Society of Radiology
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• v.81 no.2
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• pp.428-435
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• 2020

Herein, we report a case of synchronous bilateral triple negative invasive ductal breast carcinoma in a patient with discrepant pathologic response to neoadjuvant chemotherapy. Right and left breast cancer stages at the initial diagnosis were T1cN0M0 and T4dN3aM0, respectively. The patient was identified as a BRCA1 mutation carrier and treated with four cycles of adriamycin and cyclophosphamide, followed by four cycles of docetaxel. Bilateral breast cancer stages decreased with the first regimen. However, the bilateral breast cancers showed discrepant responses to chemotherapy with docetaxel. The right breast cancer showed a continuous tumor volume reduction while the left breast cancer showed marked progression. Finally, the tumor size was 0.3 cm and 12 cm in the right and left mastectomy specimens, respectively. As bilateral breast cancers of the same subtype may show discrepant responses to neoadjuvant chemotherapy, close monitoring and follow-up imaging are required to avoid delayed surgery.