Earticle

Purpose: This study was performed to examine vascular pain due to gemcitabine and according to clinical factors. Methods: The survey was performed with 525 cancer patients visiting chemotherapy infusion room in one general hospital. The data were collected via self-reported questionnaire, researchers observation, and reviewing medical records. Data were analyzed descriptive statistics, ttest, Kruskal-Wallis test, Tukey test using ranks, Jonckheere-Terpstra test, and Spearman correlation analysis were used. Results: The mean scores of the intensity and onset time of vascular pain were 3.06±2.16 and 8.13±13.13 min, and each other were negative correlaton. Degree of intensity of vascular pain had a significant difference on gender (p=.003), age (p=.004), weight (p=.019), Body massindex (BMI) (p=.005), Body surface area (BSA) (p=.030), infusion time (p<.001), dose (p=.027), dose per minute (p<.001), the number of administered gemcitabine (p=.005), combination chemotherapeutic drug (p=.013) and tumor type (p=.002). Degree of onset time of vascular pain had a significant difference on infusion time (p=.044), combination chemotherapy (p=.001) and injectionsite (p=.001). Conclusion: Patients administrated gemcitabine were experiencing various vascular pain, and vascular pain had a difference on clinical factors. Therefore, oncology nurses should be considered significant clinical factors to implement effective interventions to patients administered gemcitabine.

The purpose of this study is to prepare gemcitabine-loaded poly(Llactic acid) (L-PLA) nano- and microparticles using solution enhanced dispersion by supercritical fluids (SEDS) technique. Gemcitabine is a synthetic pyrimidine nucleoside analogue with a high antitumor efficacy for ovarian, breast bladder, and pancreatic cancer. The SEDS process is a modified supercritical antisolvent (SAS) process, in which supercritical CO2 and polymer/drug solution are simultaneously introduced into a high-pressure vessel using a specially designed coaxial nozzle. The effects of temperatures, pressures, polymer molecular weight and solution concentrations on the morphology and drug entrapment efficiency of SEDS-processed particles were investigated. Our study was focused on the comparison of SEDS with ASES process.

In this study, biodegradable poly(L-lactic acid) (L-PLA) microparticles containing gemcitabine (2,2-difluorodeoxycytidine, dFdC) were prepared by a supercritical process, called aerosol solvent extraction system (ASES). ASES is a method based on solvent extraction using supercritical carbon dioxide for the preparation of microparticles and microspheres. Gemcitabine is an effective antitumor agent in the treatment of several solid tumors. However, it has problems such as short plasma half-life, rapid metabolism, and low selectivity towards tumor tissue. The influence of operating parameters such as temperature, pressure, drug/polymer feed ratio, and polymer molecular weight on the morphology and release characteristics was studied in detail. The drug recovery, entrapment efficiency, and drug release profiles were determined by HPLC assays. The drug recovery was found to be about 70~80%. The entrapment efficiency decreased with increasing temperature and drug/polymer ratio. The ASES-processed gemcitabine-loaded microparticles showed a relatively high initial burst due to the poor affinity between gemcitabine and L-PLA.

Poly(ethylene glycol)-polyester block copolymers have widely been used in biomedical and pharmaceutical fields because of their excellent biocompatibility, biodegradability, and amphiphilicity arising from phase-separated microstructures between a hydrophilic PEG block and a hydrophobic polyester block. The aims of this research are to prepare gemcitabine-loaded microparticles using methoxy poly(ethylene glycol)-poly(L-lactide) (mPEG-PLLA) diblock copolymer and to evaluate their release characteristics. We synthesized mPEG-PLLA diblock copolymers of different block lengths, and their molecular compositions and molecular weight were analyzed by 1H-NMR and GPC. W/O/W double emulsion solvent evaporation method was used to prepare gemcitabine-loaded mPEG-PLLA microparticles. The effects of various preparative parameters such as pH, salt concentration of external water phase, solvent composition of organic phase and ratio of internal/external water phase on the morphology and the encapsulation efficiency of the microparticles were investigated. The in vitro release profiles of gemcitabine from microparticles were also determined using HPLC.

The PGSS (Particles from Gas Saturated Solutions) process is a promising technique that uses supercritical fluid to produce fine particles under relatively mild operating conditions. In this technique, a supercritical fluid is dissolved into a solution or a melted material. Under the appropriate pressure and temperature conditions, this mixture is rapidly depressurized through a nozzle, resulting in the formation of fine solid particles. Gemcitabine is a pyrimidine nucleoside analogue with a high antitumor efficacy for the treatment of ovarian, breast, bladder, and pancreatic cancers. In this study, gemcitabine-loaded polymer particles were parepared using a PGSS technique. The effect of temperature, pressure, the type of biodegradable polymers, and micronization of gemcitabine using a supercritical ASES (Aerosol Solvent Extraction System) process on the morphology and drug entrapment efficiency of PGSS-processed particles were investigated. The entrapment efficiency of gemcitabine from particles was also determined using HPLC assay.

In this study, gemcitabine-loaded poly(L-lactic acid) (L-PLA) nano- and microparticles were prepared using solution enhanced dispersion by supercritical fluids (SEDS) technique. Gemcitabine is a synthetic pyrimidine nucleoside analogue with a high antitumor efficacy for ovarian, breast bladder, and pancreatic cancer. The SEDS process is a modified supercritical antisolvent (SAS) process, in which supercritical CO2 and polymer/drug solution are simultaneously introduced into a high-pressure vessel using a coaxial nozzle. The effects of CO2 flowrate, solution flowrate, temperature, pressure, polymer molecular weight and solution concentration on the morphology and drug entrapment efficiency of SEDS-processed particles were investigated. The entrapment efficiency and in vitro release profiles of gemcitabine from microparticles were also determined using HPLC. Our study was focused on the comparison of SEDS with ASES process.

화학요법 (chemotherapy)으로 사용되는 항암제 중 상당수는 강한 세포 독성을 가지고 있으며, 짧은 반감기 또는 체내에 서의 신진대사로 인해 낮은 생체이용률을 보인다. 따라서 약 물의 높은 항암 효과에도 불구하고 약물의 과다복용에 따른 부작용이 심각한 것으로 알려져 있다. 약물의 과다 복용에 의한 부작용을 최소화하고 약물의 효과를 극대화하기 위한 방법으로 약물을 생분해성 고분자 내에 봉입하여 미립자를 제조함으로써 특정 시간 동안 원하는 농도로 약물을 방출시 키는 고분자 미립자 약물전달시스템 기술 개발에 대한 많은 연구가 진행되고 있다 [1-3]. 이와 같은 약물전달시스템을 개발하기 위해서는 여러 가지 기술이 필요하지만, 가장 중요 한 핵심기술은 약물과 고분자 (약물전달체) 및 이들의 혼합 물을 원하는 크기와 형태 및 약물의 봉입률을 갖는 미립자로 제조하는 것이다. 고분자 미립자 약물전달시스템에서 일반적으로 사용되고 있는 생분해성 고분자로는 poly (lactic acid) (PLA), poly (glycolic acid) (PGA), 이 둘의 공중합체인 poly (lactic-coglycolic acid) (PLGA), poly (ε-caprolactone), polyanhydride, poly (ortho ester) 등이 있다 [2]. 특히 PLA와 PLGA 같은 polyester계 생분해성 고분자가 전달체로 널리 사용되고 있 는 이유는 오랫동안 체내에 유지되며 생체 내에서 고분자가 이물질 반응을 거의 일으키지 않는 생체적합성과 일정한 기능을 다한 후에는 신진대사를 통해 이산화탄소와 물로 분해 되어 체외로 배출되는 생분해성의 특성을 가지기 때문이다. 고분자 미립자를 제조하는데 많이 사용되고 있는 방법으 로는 용융법, 에멀젼법, 상분리법, 용매 증발 및 추출법, 분무 건조법 등이 있다 [4-6]. 이들 방법은 과량의 에너지 소비, 다 량의 폐유기용매 및 폐수의 배출로 인한 환경오염, 낮은 수율, 낮은 약물 봉입률, 고비용, 열 민감성에 의한 약물의 변성, 입자제조 후 유기용매의 잔존 등의 많은 문제점을 가지고 있 다. 이와 같은 문제점을 해결하기 위한 여러 방법 중 환경친 화적 단일공정 기술로서 초임계 유체 (supercritical fluid)를 이용한 미립자 제조기술에 대한 관심이 증대하고 있다. 초임계 유체란 어떤 물질의 임계점 (critical point) 이상의 온도와 압력 조건에서 존재하는 유체로서 액체와 기체의 중 간적인 물리적 특성을 가지고 있다. 초임계 유체는 높은 용해 도, 선택도, 압축성, 감압에 따른 자발적 분리성 등의 열역학 적 특성과 낮은 표면장력과 점도, 높은 확산 계수의 이동특 성을 갖고 있어 미립자의 제조에 매우 유리하다 [5,7-10]. 또한, 온도와 압력의 미세 조절을 통해 용해도, 확산도 등의 유체 성질을 쉽게 조절할 수 있으며 감압에 의해 사용된 유기 용매와 이산화탄소를 쉽게 분리하여 회수할 수 있다. 초임계 유체로는 특히 이산화탄소를 많이 사용하는데, 이 는 비교적 낮은 임계온도 (31℃)와 임계압력 (73.8 bar)을 가지고 있으며, 인체에 무해하고 가격이 저렴할 뿐만 아니라 폭발성 및 발화 위험이 거의 없기 때문이다. 따라서 미립자 제조에 있어 단일 공정으로 이산화탄소를 이용한 초임계 유체 공정은 다양한 분야에서 주목받고 있는 기술이다 [5,7-10]. 초임계 유체 공정에서 초임계 유체는 고분자 및 약물의 용매 또는 역용매로 사용되며, 온도와 압력을 조절하여 초임계 유 체의 용해도를 제어함으로써 고분자와 약물 및 이들의 혼합 물을 침전 또는 재결정시켜 미립자를 제조한다. 본 연구에서 사용한 초임계 유체 기술은 aerosol solvent extraction system (ASES) 공정으로서, 초임계 유체를 대상 용질에 대한 역용매로 사용하여 미립자를 제조하는 방법이다. 이 공정에서 고분자와 약물이 용해되어 있는 용액이 미세 노즐을 통하여 초임계 유체 내로 액적 (droplet)의 형태로 분사되면 액적 내의 유기용매는 빠른 속도로 초임계 유체 상으로 증발되고, 동시에 초임계 유체는 액적 내부로 확산 되어 액적이 팽창되고, 결과적으로 액적 중 고분자와 약물에 대한 용매의 용해도가 급격히 감소하여 매우 빠른 속도로 미립자가 형성된다 [7-10]. 젬시타빈 (gemcitabine, 2',2'-difluorodeoxycytidine)은 deoxycytidine 유도체로 비소형 세포 폐암, 췌장암, 난소암, 유방암 등의 고형종양에 대하여 항암 작용을 가지고 있는 것으로 알려져 있다 [11-15]. 젬시타빈은 암세포의 DNA 합 성을 방해함으로써 암세포를 사멸시키는 작용을 한다. 일반 적으로 수액과 함께 섞어서 혈관으로 투여되며, 1,000 mg/m2 의 양을 매주 한 차례씩 30분 동안 3주간 투여하고 주사한 후 4주째에는 약물의 투여를 중단하는 방법으로 이용된다. 그러나 젬시타빈은 주로 항암 활성이 없는 2'-deoxy-2', 2'-difluoruridine으로 대사되어 혈장으로부터 빠르게 제거되며, 이로 인해 30-90분의 짧은 반감기를 갖기 때문에 많은 약물의 투여가 요구되어 부작용이 심각한 문제가 될 수 있 다. 주요 부작용으로는 오심, 구토, 골수 기능 저하 등을 들 수 있다. 현재 젬시타빈을 기반으로 하는 여러 항암제의 조합 이 임상시험에 적용되고 있으며, 방사선 치료와도 병합하여 사용되고 있다 [16]. 본 연구에서는 서방성 약물방출 미립자를 제조하기 위하 여 여러 종류의 생분해성 고분자 중 비교적 분해속도가 느린 poly (L-lactic acid) (PLLA)을 선택하여 실험을 수행하였다. 서방성 약물방출 미립자를 제조하는 방법으로는 기존의 미립 자 제조 방법들의 문제점을 개선할 수 있는 대체 공정으로 최근 많이 연구되고 있는 초임계 유체 기술의 하나인 ASES 공정을 사용하였다. 초임계 ASES 공정에서 생분해성 고분자 인 PLLA와 친수성 약물인 젬시타빈을 이용해 온도, 압력, 이산화탄소와 용액의 유량, 용액의 농도, 약물/고분자 투입 비율 등의 공정 및 조성 (formulation) 변수가 제조된 미립자 의 크기, 형태, 봉입효율 및 약물함량에 미치는 영향과 약물 방출특성을 확인함으로서 초임계 유체 공정의 서방성 약물 방출 미립자제조에 대한 적용가능성 여부를 조사하였다.

In this study, poly (L-lactic acid) (PLLA) microparticles containing gemcitabine hydrochloride were prepared by a supercritical fluid process, called aerosol solvent extraction system (ASES), utilizing supercritical carbon dioxide as antisolvent. The influence of process parameters such as temperature, pressure, CO2 and solution flow rate, solution concentration, and feed ratio of drug to polymer on the morphology and characteristics of the microparticles was studied in detail. The gemcitabine-loaded microparticles exhibited a spherical shape with a smooth surface. The entrapment efficiency of gemcitabine increased with increasing temperature, solution concentration and CO2 flow rate and with decreasing drug/polymer feed ratio. The maximum drug loading obtained from the ASES process was found to be about 11%. The ASES-processed PLLA microparticles containing gemcitabine showed a relatively high initial burst due to the presence of surface pores on the microparticles and the poor affinity between drug and polymer.

Gemcitabine (2,2-difluorodeoxycytidine, dFdC) is an effective antitumor agent in the treatment of several solid tumors. However, it has been reported that gemcitabine has problems such as short plasma half-life, rapid metabolism, and low selectivity towards tumor tissue. In this study, gemcitabine-loaded biodegradable poly(L-lactic acid) (L-PLA) microparticles were prepared by a supercritical fluid process, called aerosol solvent extraction system (ASES). ASES is a supercritical technique based on solvent extraction using supercritical carbon dioxide for the preparation of microparticles and microspheres. The influence of operating parameters such as temperature, pressure, concentration, CO2 flow rate and solution flow rate on the morphology and characteristics of the microparticles was studied in detail. The drug entrapment efficiency and loading efficiency were determined by HPLC assays. The entrapment efficiency increased with increasing temperature, concentration and CO2 flow rate. The ASES-processed drug-loaded microparticles showed a relatively high initial burst due to the presence of pores of the microparticles and the poor affinity between gemcitabine and L-PLA.

In this study, gemcitabine-loaded methoxy poly(ethylene glycol)-b-poly(L-lactide) (MPEG-PLLA) microparticles with different PEG block lengths were prepared by a W/O/W double emulsion technique. The present study focuses on the investigation of the influence of various preparative parameters such as the ratio of internal water phase and oil phase, polymer concentration, solvent composition of organic phase and salt concentration of external water phase on the morphology and encapsulation efficiency of the microparticles. The microparticles fabricated at high volume ratios of internal water phase to oil phase and at high polymer concentrations showed a relatively high encapsulation efficiency and low porosity. When a dichloromethane/ethyl acetate mixture was used as solvent, both the encapsulation efficiency and drug loading of the microparticles decreased as the level of ethyl acetate increased. The addition of a salt (NaCl) to the external water phase significantly improved the encapsulation efficiency up to 40%, and the microparticles became more spherical with their size and porosity decreased.

대퇴골 전이를 동반한 비소세포폐암 환자에서 전이 부위에 대한 방사선 치료 후 시행한 항암화학요법 도중, gemcitabine으로 인한 방사선 회귀 피부, 근육염이 발생하였다. 대퇴부의 부종, 발적과 통증 등은 스테로이드 사용 후 모두 사라졌으며, gemcitabine 투여를 중지한 이후 현재까지 재발이 없었다.

A radiation recall reaction refers to an inflammatory reaction at previous irradiated areas subsequent to the administration of a variety of pharmacological agents. The skin is the major site of radiation recall reactons with the muscle and internal organs being less commonly affected. These reactions usually occur days to weeks after exposure to the causative agents. We report a case of gemcitabine-induced radiation recall dermato-myositis the developed in a female patient with a metastatic non-small cell lung cancer. She had received a palliative radiation therapy of 3900 cGy to the metastatic lesion on the femur shaft prior to chemotherapy. The pain, swelling and erythema of the left thigh resolved after the cessation of gemcitabine and the use of a systemic steroid.

배 경 : Gemcitabine, paclitaxel, docetaxel, vinorelbine, irrinotecan 새로운 항종양제의 출현으로 일차 치료의 효과가 증대 되고 있고 재발시에도 좋은 신체 활동도를 보이고 있어서 이차 치료의 대상군도 늘어나는 효과를 보이고 있다. 치료의 필요성은 증대 되고 있지만 현재까지 표준 치료가 확립되지 않은 상황에서 Gemcitabine과 Vinorelbine 모두 독성이 강하지 않아서 혼합 요법이 가능한 장점이 있고 비소세포폐암에 대한 효과도 입증이 되어있어서 본 연구는 반응이 없거나 반응을 보인후에 재발된 진행된 비소세포 폐암에 gemcitabine과 vinorelbine 혼합 요법을 시행하여서 치료 반응률과 생존율 그리고 부작용을 평가하였다. 대상 및 방법 : 2000년 6월부터 2004년 3월까지 충남대학교병원에 내원하여 진행성 비소세포 폐암 IIIA/IIIB, IV로 진단을 받고 일차 항암화학요법치료를 받은 환자중에 초기 치료에 반응이 없거나, 치료에 반응이 있었으나 병이 진행된 환자로 추적 관찰 기간이 6개월 이상인 환자를 대상으로 생존율과 반응률 그리고 독성을 분석하였다. 결 과 : 총 치료 반응률은 17%, 반응 유지기간의 중앙값은 3.1개월(1-10개월)이었고 생존기간의 중앙값은 8.2개월(1-23개월) 그리고 1년 생존율은 35%였다. 항암화학요법에 의한 독성은 3도 이상의 중성구 감소가 12%, 오심과 구토가 12.5% 였다. 결 론 : 일차 치료에 반응이 없거나 재발한 비소세포 폐암환자의 이차 치료로 gemcitabine과 vinorelbine 혼합요법은 효과적이라고 생각되며 향후 3상 연구를 통한 다른 약제와의 비교 연구가 필요하다고 생각된다.

Background : Both gemcitabine and vinorelbine are effective anticancer drugs with mild toxicity on non-small cell lung cancer, and monotherapy of these drugs are effective as a second-line chemotherapy. The aim of this trial was to assess the response and toxicity of a combination of gemcitabine and vinorelbine in patients of previously treated for non-small cell lung cancer. Materials and Methods : 24 patients, initial stage III A/B,IV and previously treated with platinium and taxane based regimens, were enrolled from June 2000 to March 2004. The regimens consisted of vinorelbine $25mg/m^2$ followed by an infusion of gemcitabine $1000mg/m^2$ on day 1 and day 8 every three weeks. This course was repeated more than twice. Results : Twenty-four patients were analyzed for the response, survival rate, and toxicities. The overall response was 17% with a complete remission rate of 4%. The median time-to progression (TTP) was 3.1 months (95%, CI 1-10months), and the survival time was 8.2 months (95%, CI 1-23 months). The grade 3/4 toxicities encountered were neutropenia (12.5%), anemia (0%), thrombocytopenia (0%). Non-hematological 3/4 toxicities were not observed. Conclusion : A combination of gemcitabine and vinorelbine in patients previously treated for non-small cell lung cancer provides a relatively good response rate, and a low toxicity profile. However, further study will be needed to confirm its effectiveness.

The nucleoside analogue gemcitabine (2', 2-difluorideoxycytide) is potential against a wide variety of solid tumors and considered to be one of the most active drugs in the treatment of non-small cell lung cancer (NSCLC). In this study, we investigated the signals of gemcitabine-induced apoptosis, especially in point of caspase pathway in A549. We exposed A549 cells to gemcitabine for dose/time dependent manner and the results showed that gemcitabine induced apoptotic cell death in a time/dose-dependent manner. We also treated to gemcitabine and Z-VAD-fmk as a pan-caspase inhibitor for 24 hours. Gemcitabine alone induced 35.3% cell death, and co-treatment with gemcitabine and Z-VAD-fmk induced 15.1% apoptotic cell death. Our results demonstrated that Z-VAD-fmk as a pan-caspase did not completely block the gemcitabine-induced apoptosis. Western blotting analysis showed that gemcitabine increased caspase-3, active caspase-8, p21 and p53 protein expressions in A549. Co-treatment with Z-VAD-fmk completely blocked caspase-3 and active caspase-8 protein expressions, but did not change the level of p21 and p53 protein expressions. Our data indicate that gemcitabine induced apoptosis through caspase-dependent and -independent pathways in A549.

Gemcitabine은 최근 사용이 증가되고 있는 항암제로서 호흡기 부작용이 흔히 발생하나 대부분 일시적이고 자연 관해된다. 하지만 드물게 gemcitabine에 의한 심각한 폐 독성이 발생할 수 있으며, 이는 조기 진단 및 치료가 중요하다. 저자들은 gemcitabine 치료 후 발생한 중증 약물 유발성 간질성 폐렴 환자에서 스테로이드 치료 후 호전된 증례를 경험하였기에 보고하는 바이다.

Gemcitabine is an effective newly developed chemotherapeutic agent, which is increasingly being used to treat non-small cell lung, ovarian and breast cancers. Pulmonary toxicity is usually self-limiting mild dyspnea, bronchospasm, but severe pulmonary toxicity is rarely reported. Herein, we report drug induced interstitial lung disease associated with gemcitabine treatment. High resolution computerized tomogram (HRCT) showed an increased ground glass opacity and thickened septal lines. The patient showed a rapid good response with prednisolone treatment.

광범위 수술 후 platinum과 paclitaxel의 항암화학요법은 상피성 난소암 환자의 생존율을 향상시켰다. 그러나 적절한 종양감축술과 platinum을 기본으로 하는 다제병용 화학요법에도 불구하고 진행성 병변을 가진 환자의 대부분에서 종양의 재발과 진행을 경험하며, 보다 효과적인 이차 항암화학요법의 필요성이 대두되었다. 인제대학교 상계백병원에서 진단 및 일차치료 후 재발한 네 명의 진행성 상피성 난소암 환자들이 gemcitabine을 투여 받았으며, gemcitabine은 체표면적 (m2)당 1000 mg을 30분에 걸쳐 정주하였으며, 3주간 매주 1차례 (1일째, 8일째, 15일째) 정주하고 4주째 쉬는 것을 1주기로 하여 28일마다 반복하여 투약하였다. 한 명의 환자는 완전관해를 보이고 다른 한 명의 환자는 안정성 병변의 소견을 보인 반면 두 명의 환자에서는 진행성 병변의 소견을 보였으며, 이들 중 한 명은 치료 2개월 뒤 사망하였다. Grade 3의 백혈구 감소증은 과립구 형성 자극인자 (G-CSF)의 투여로 치료되었으며, 이전의 항암화학요법으로 소실된 머리카락은 네 명 모두에서 회복되었다. 저자 등은 paclitaxel과 cisplatin의 항암화학요법 후 재발한 난소암 환자에서 gemcitabine 단독 항암화학요법을 시행한 4예를 보고하는 바이다.

Adjuvant multiagent chemotherapy with platinum and paclitaxel after optimal cytoreductive surgery decisively improved survival rates of patients with epithelial ovarian carcinoma. However, more than two- thirds of patients with advanced disease will encounter tumor progression, underlining the need for effective second-line strategies. Continued efforts to discover new active agents for the treatment of patients with ovarian carcinoma had identified gemcitabine. Four patients with epithelial ovarian carcinoma, who were treated in Inje University Sanggye Paik Hospital and recurred thereafter received gemcitabine 1,000 mg/m2 as a 30 min intravenous infusion on days 1, 8, and 15, which was repeated every 28 days. The disease progressed in two patients, while one showed stable disease and another reached complete response. One patient expired of disease two months after the completion of therapy. Grade 3 leukopenia was successfully managed using G-CSF. Regrowth of hair lost during previous chemotherapy occurred in all subjects. We report four cases of advanced recurrent ovarian carcinoma which were treated with gemcitabine.

Objectives: This study was aimed to report a patient with metastatic pancreatic cancer treated with modified Bangam-tang and Gunchil-dan in conjunction with gemcitabine. There were better survival-related outcomes compared to gemcitabine alone. Methods: The patient with metastatic pancreatic cancer received gemcitabine as palliative chemotherapy since June 2016 concurrent with modified Bangam-tang and Gunchil-dan since October 2016 to October 2017. To evaluate the effect of treatment, tumor markers (carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)), Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and overall survival were checked. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: After 12 months with the combination treatment, levels of CA19-9 were decreased from 8747 to 265.7 ng/ml and CEA from 42.2 to 6.5 U/ml. Clinical partial response state was shown until May 2, 2017 and stable disease state was maintained from August 4, 2017. In March 2018, the patient got an operation including pancreatectomy and diagnosed with no evidence of disease state in September, 2018. In conclusion, it showed the overall survival of 29 months from June, 2016 to November, 2018. Serious adverse events were not identified. Conclusions: This study suggested that combined treatment with modified Bangam-tang and Gunchil-dan may show better outcome in patient with metastatic pancreatic cancer than gemcitabine alone.

Purpose: This analysis was conducted to evaluate the cost-effectiveness of gemcitabine-cisplatin chemotherapy for non small-cell lung cancer patients in an outpatient setting compared with the traditional inpatient setting. Methods: A cost-effective analysis was conducted from a societal perspective. The effects of treatment, which was measured as an adverse event rate, were abstracted from a published literature search and empirical data from one university hospital. The costs included both direct and indirect costs. Direct costs included hospitalizations, outpatient visits, and lab tests. Pharmaceutical costs were excluded in analysis because they were same for both options. Indirect costs included productivity loss of patients as well as care-givers. In order to determine the robustness of the results, sensitivity analysis on treatment protocol was conducted. Results: Literature search showed no difference in adverse effect rates between inpatient treatment protocol and outpatient treatment protocol. Therefore, this analysis is a cost-minimization analysis. Cost-savings in the outpatient setting was 555,936 won for one treatment cycle. Our sensitivity analysis indicated that the outpatient chemotherapy still showed cost-savings, regardless of changes in treatment protocol. Conclusion: The outpatient gemcitabine-cisplatin chemotherapy for non small-cell lung cancer resulted in cost savings compared to inpatient chemotherapy. More importantly, outpatient chemotherapy could improve the utilization of health service resources in terms of available beds.

배 경 : 새로운 항암제의 사용으로 비소세포 폐암에서 1차 항암 치료의 효과는 많이 향상 되었지만 많은 환자에서 치료 중 혹은 치료 후에 폐암이 진행하거나 재발되고 있다. 최근 환자의 체력 및 영양 상태의 향상으로 폐암의 진행 및 재발 후에도 신체 수행 상태(performance status)가 양호하여 2차 항암 치료의 대상 환자가 늘어나는 추세이다. 그러나 아직까지 표준화된 2차 항암 치료가 없는 실정으로 gemcitabine과 vinorelbine의 병합 요법은 비교적 다른 기전의 독성을 보여 병합 요법으로서의 가능성을 높여 주었다. 이에 저자들은 1차 항암 요법에 반응을 보이지 않거나 재발한 진행성 비소세포 폐암 환자를 대상으로 gemcitabine과 vinorelbine 병합 요법을 시행하여 치료 반응율, 생존율 및 독성에 대해 연구하였다. 대상 및 방법 : 2000년 12월부터 2003년 7월까지 고려대학교 의료원에 내원하여 비소세포 폐암으로 확진 받은 환자 중 진단 당시 IIIB, IV병기로 platinum을 기반으로 docetaxel 혹은 paclitaxel의 2제 복합 항암 요법을 1차 치료로 시행한 환자 중 진행하거나 재발한 환자들을 대상으로 gemcitabine과 vinorelbine 병합 요법의 치료 반응율, 생존율 및 독성을 분석하였다. 결 과 : Vinorelbine과 gemcitabine 병합 항암화학 요법은 총 215회가 시행 되었고, 환자당 시행된 평균값은 3.6회였다. 주요 반응에 해당하는 관해율은 10%였다. 1년 생존율은 32.9% 였으며, 생존 중앙값은 10.1개월이었다. 관해 지속 기간 중앙값은 3.8개월이었다. 대부분에서 경도의 오심과 구토, 탈모증이 관찰되었으며 WHO grade 3의 오심, 구토는 2예(3%)였으며, grade 4의 오심, 구토는 없었다. Grade 3 백혈구 감소가 33.3%, grade 4가 11.7%로 비교적 흔히 발생하였다. 호중구 감소가 동반된 폐렴으로 사망이 1예 보고되었다. 결 론 : Platinum을 기반으로 하는 1차 항암 치료 후 재발하거나 진행한 비소세포 폐암 환자에서 gemcitabine과 vinorelbine 병합 항암 요법은 비교적 효과적이고 안전한 항암 치료법으로 사료된다.

Backgroud : Lung cancer is the leading cause of cancer deaths in Korea and the number of lung cancer deaths is increasing. The higher response rates, decreased toxicity and improved performance status of the first-line treatments have resulted in an increased number of patients becoming candidates for second-line therapy. Several new antineoplastic agents, including gemcitabine, docetaxel and paclitaxel, have recently demonstrated second-line activity. This phase II study evaluated the efficacy and toxicity of gemcitabine and vinorelbine as combination chemotherapy for Korean patients with NSCLC as a second-line treatment. Methods : Sixty response-evaluable patients were enrolled from December 2000 to July 2003. We conducted a phase II study of a combination gemcitabine and vinorelbine chemotherapy for patients with histologically confirmed NSCLC that was stage IIIB and IV disease at the time of diagnosis, and the disease had progressed onward or the patients had relapsed after first-line platinum-based chemotherapy. They were treated with intravenous gemcitabine $1000mg/m^2$ and intravenous vinorelbine $25mg/m^2$ on days 1 and 8. This chemotherapy regimen was repeated every 3 weeks. Results : A total of 215 cycles of treatment were given and the mean number of cycles was 3.6 cycles. All the patients were evaluable for the toxicity profile. The response rate was 10% according to the WHO criteria. The median progression free survival was 3.8 months and the median survival time was 10.1 months. The 1-year survival rate was 32.9%. Grade III and IV neutropenia were seen in 20 (33.3%) and 7 (11.7%) patients, respectively. Conclusion : The combination of gemcitabine and vinorelbine is active and well tolerated as a second-line therapy for patients with advanced nonsmall cell lung carcinoma.