• Radiation Oncology Journal
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• 제17권2호
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• pp.113-119
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• 1999

목적 :국소적으로 진행된 자궁경부암 환자에서 저용량의 Cisplatin을 방사선민감제로 사용하여 방사선치료와 동시 치료하였을 때의 급성독성 평가와 초기 반응을 평가하기 위하여 연구를 시행하였다. 대상 및 방법 : 본 연구는 1996년 12월부터 1999년 1월까지 FIGO Stage IIB-IIIB의 진행된 자궁경부암 환자 38명을 대상으로 하였다. 16명은 자궁경부암의 크기가 4cm이상인 환자들로 방사선 치료와 저용량의 cisplatin을 매일 동시에 치료 하였으며, 나머지 환자에선 방사선 치료 단독으로 치료하였다. 방사선치료는 골반강에 외부 방사선치료로 4500 cGy(3060cGy시행이후 midline block 추가), 자궁옅조직으로 침범이 있는 경우에는 자궁옅조직으로 방사선치료 부위를 줄여 900-1000cGy 추가치료를 시행하였고, 내부치료는 Ir$^{192}$고선량 근접 치료기(micro-Selectron HDR)로 6극회의 강 내조사(point "A"에 3000 to 3500cGy, 500cGy/fx, 2회/week)를 시행하였다. 방사선치료와 저용량의 cisplatin을 동시에 사용한 군에서는 방사선치료 첫날부터 방사선치료 20일째 되는 날까지 저용량의 cisplatin 10mg을 방사선치료 30분 전에 투여하였다. 급성독성의 평가는 expanded common toxicity criteria of the NCI Clinical Trial을 이용하였다. 초기반응의 평가는 방사선치료 종료이후 최소 4주이상의 추적조사가 가능한 사람들을 대상으로 시행되었다. 결과 : 급성독성 평가는 전체 38명에서 평가 가능하였으며, 방사선치료와 저용량의 cisplatin을 병용한 군에서 16명 중 6명(37.5$\%$)에서, 방사선 단독으로 치료한 군에서는 22명중 1명(6.2$\%$)에서 3등급 이상의 백혈구감소를 보였으며, 통계학적으로 의미있는 차이를 보였다 (P=0.030). 3등급 이상의 급성 위장간 독성은 저용량의 cisplatin을 병용한 군에서만 4명이 있었으나, 2-3일의 치료 중단이후 증상이 완화되어서 치료를 계속할 수 있었으며, 치료중 5kg이상의 체중감소는 방사선치료와 저용량의 cisplatin을 병용한 군에서는 16명중 3명(18.7$\%$), 방사선 단독으로 치료한 군에서는 22명중 2명(9.1$\%$)으로 통계학적으로 의미 있는 차이를 보이지 않았다(P=0.63). 초기반응은 추적조사가 4주 이상 가능하였던 34명을 대상으로 하였으며, 저용량의 cisplatin을 병용한 군에서 14명중 11명 (78$\%$), 방사선 단독으로 치료 군에서 20명중 16명(80$\%$)으로 통계학적으로는 의미있는 차이를 보이지 않았다(P=0.126). 결론 :국소 진행된 자궁경부암에 대한 방사선치료와 저용량의 cisplatin 병용요법 치료시 3등급 이상의 백혈구감소가 방사선치료 단독으로 치료시보다 많았으나, 1주 이하의 치료중단 이후 치료를 계속 할 수 있었으며, 4등급 이상의 백혈구감소와 치료에 의한 사망은 없었다. 초기반응에 대한 평가는 저용량의 cisplatin병용 군에서 4cm 이상의 자궁경부암을 가진 환자가 많음에도 불구하고 양 군에서 비슷한 정도의 반응을 보였으므로 진행된 자궁경부암의 치료에서 저용량의 cisplatin을 방사선민감제로 사용하여 치료결과의 향상을 기대할 수 있게 되었다. 따라서 저용량의 clsplatin과 방사선치료를 병용요법하였을 때의 치료효과를 판정하기 위해서는 phase III study가 필요하다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9627-9630
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• 2014

Background: Although efficacy of aprepitant for suppressing emesis associated with single-dose cisplatin has been demonstrated, there are limited data on the antiemetic effect of this oral neurokinin-1 receptor antagonist during daily administration of cisplatin. Accordingly, we investigated the efficacy and safety of aprepitant in patients with head and neck cancer (HNC) receiving combination therapy with cisplatin and 5-FU (FP therapy). Materials and Methods: Twenty patients with HNC were prospectively studied who received a triple antiemetic regimen comprising granisetron ($40{\mu}g/kg$ on Days 1-4), dexamethasone (8 mg on Days 1-4), and aprepitant (125 mg on day 1 and 80mg on days 2-5) with FP therapy (cisplatin $20mg/m^2$ on days 1-4; 5-FU $400mg/m^2$ on days 1-5) (aprepitant group). We also retrospectively studied another 20 HNC patients who received the same regimen except for aprepitant (control group). Results: For efficacy endpoints based on nausea, the aprepitant group showed significantly better results, including a higher rate of complete response (no vomiting and no salvage therapy) for the acute phase (p=0.0342), although there was no marked difference between the two groups with regard to percentage of patients in whom vomiting was suppressed. There were no clinically relevant adverse reactions to aprepitant. Conclusions: This study suggested that a triple antiemetic regimen containing aprepitant is safe and effective for HNC patients receiving daily cisplatin therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8591-8594
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• 2014

Background: Lung cancer is the most common cancer in males worldwide. The principal mode of treatment in the early stage of non-small cell lung cancer (NSCLC) is surgery. However, five-year survival is only about 15% for all stages. The aim is to investigate the effect of daily low dose cisplatin concurrently with radiation therapy in advanced NSCLC patients with poor performance status. Materials and Methods: Ten patients diagnosed as inoperable Stage IIIB NSCLC with comorbid disease were assessed retrospectively in Bezmialem Vakif University, Faculty of Medicine, Department of Radiation Oncology, between 2011 to 2013. ECOG performance status was between 3 and 4. Cisplatin was administered at $6mg/m^2$ daily, for 5 days a week concurrently with radiotherapy using 160-200 cGy daily fractions, 54 Gy being the lowest and 63 Gy being the highest dose. Results: Complete response at the primary tumour site was obtained in 20% patients. Grade I esophagitis was seen 70 percent of patients, and the grade II haematological toxicity rate was 20 %. Median survival time was 7 months. Conclusions: Median survival time was reasonable, despite the patients ECOG performance status of 3-4, which is similar to groups even without comorbid disorders in comparison to other published papers in the literature. Acceptable toxicity, high response rates and quality of life of patients are the other favourable features.

• Tuberculosis and Respiratory Diseases
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• 제63권2호
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• pp.154-164
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• 2007

배경: Irinotecan hydrochloride는 topoisomerase I inhibitor로서 소세포 폐암에 효과적인 약제로 알려져 있다. Irinotecan은 cisplatin과 더불어 방사선감작물질로 작용하기도 한다. 본 연구는 이전에 치료받은 경험이 없는 제한성 병기의 소세포 폐암 환자에서 irinotecan과 cisplatin(IP)의 방사선 동시화학요법의 효과를 평가하기 위하여 시행되었다. 방법: 2002년 12월부터 2004년 11월까지 충남대학교 병원에서 새로이 제한성 병기의 소세포 폐암으로 진단된 24명의 환자들을 대상으로 하였다. Irinotecan $60mg/m^2$을 제 1일과 제 8일째 투여하였고 cisplatin $60mg/m^2$을 제 1일째 투여하였으며 매 3주 간격으로 시행되었다. 제 3차 항암화학요법을 시작하는 날과 동시에 과다 분할방사선 치료(twice-daily thoracic irradiation; 45 Gy total)을 시작하였다. 예방적 전 뇌 방사선 조사(Prophylactic cranial irradiation)가 방사선 동시화학요법이 끝난 후 완전반응(complete response)을 나타낸 환자에서 시행되었다. 제 2차 항암요법과 제 6차 항암요법이 끝난 후에 흉부 전산화 단층촬영과 기관지경 등을 통한 병기의 재평가가 이루어졌다. 결과: 병기의 재평가는 19명의 환자에게 이루어졌다. 중앙 추적관찰기간은 12.5개월이고 전체 99회의 항암치료가 시행되었다. 평균 한 환자당 5.2회의 항암치료가 시행되었다. 실제 용량강도는 cisplatin $19.6mg/m^2$/week과 irinotecan $38.2mg/m^2$/week이었다. 9명의 환자가 완전반응을 보였고 10명의 환자가 부분반응(partial response)을 보여서 전체 반응률은 95%였다. 3에서 4도의 혈액학적 독성은 백혈구 감소증(35% of cycles), 빈혈(7% of cycles), 혈소판 감소증(7% of cycles) 등으로 나타났다. 3에서 4도의 비 혈액학적 독성은 설사(5% of cycles)였다. 3에서 4도의 방사선 식도염(10% of patients)을 제외하고는 과다 분할 방사선 치료를 이용한 방사선 동시 화학요법의 기존의 방법과 독성 면에서는 큰 차이가 없었다. 치료와 관련된 사망은 관찰되지 않았다. 평가가 가능한 환자들에서 1년 생존율과 2년 생존율은 각각 89% (16/18)와 47% (9/18)였다. 결론: 3주 간격으로 시행된 irinotecan과 cisplatin을 이용한 과다분할 방사선 동시 요법은 제한성 병기의 소세포 폐암 환자에서 부작용은 높지 않으면서 효과적인 치료법으로 고려될 수 있을 것이다.

• 한국임상약학회지
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• 제22권4호
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• pp.356-366
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• 2012

Background: Chemotherapy-induced peripheral neuropathy (CIPN) involving sensory and motor nerve damage or dysfunction is a common and serious clinical problem that affects many patients receiving cancer treatment. This condition may pose challenges for the clinician to diagnose and manage, particularly in patients with coexisting conditions or disorders that involve the peripheral nervous system. Many chemotherapeutic agents used today are associated with the development of serious and dose-limiting CIPN that can adversely affect the administration of planned therapy and can impair quality of life by interference with the patients' activities of daily living. The most important clinical objective in the evaluation of patients with CIPN is to determine their level of functional impairment involving activities of daily living. These findings are used to make medical decisions to continue, modify, delay, or stop treatment. The most commonly reported drugs to cause CIPN include taxanes, platinum agents, vinca alkaloids, thalidomide, and bortezomib. We aimed to determine PN incidence during cisplatin, carboplatin and oxaliplatin administration. Methods: We collected data from 125 patients who received at least one cycle of cisplatin, carboplatin or oxaliplatin. They completed a self-reported questionnaire and items related to their disease and peripheral neuropathy. The investigators filled in part of items about disease and treatment. Patient Neurotoxicity Qeustionnaire developed by Bionumerik company were applied for PN assessment. Results: The incidences of sensory neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 23%, 56% and 50%. The incidences of motor neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 18%, 42% and 19%. The incidences of severe neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 13%, 28% and 14%. The incidences of PN were associated with cumulative dose but not age, gender and concurrent illness. 19.2% of the patients (24/125) were prescribed with gabapentin, nortriptyline or gabapentin plus nortriptyline to reduce these peripheral symptoms and 75% of the patients answered the drug were effective. Conclusion: Incidence of PN after cisplatin or oxaliplatin administration is cumulative dose-related. Physician-based assessments under-reported the incidence and severity of CIPN. To overcome this limitation, diagnostic tools specifically designed to assess peripheral neuropathy severity associated with chemotherapy must be developed.

• The Korean Journal of Physiology and Pharmacology
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• 제28권2호
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• pp.145-152
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• 2024

Chemotherapy-induced cognitive impairment is recognized as the most typical symptom in patients with cancer that occurs during and following the chemotherapy treatment. Recently many studies focused on pharmaceutical strategies to control the chemotherapy side effects, however it is far from satisfactory. There may be a need for more effective treatment options. The aim of this study was to investigate the protective effect of exercise on cisplatin-induced neurotoxicity. Eight-week-old C57BL6 mice were separated into three group: normal control (CON, n = 8); cisplatin injection control (Cis-CON, n = 8); cisplatin with aerobic exercise (Cis-EXE, n = 8). Cisplatin was administered intraperitoneally at a dose of 3.5 mg/kg/day. The Cis-EXE group exercise by treadmill running (14-16 m/min for 45 min daily, 3 times/week) for 12 weeks. Compared to the CON group, the cisplatin injection groups showed significant decrease in body weight and food intake, indicating successful induction of cisplatin toxicity. The Cis-CON group showed significantly increased levels of pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α in the hippocampus, while the Cis-EXE group was significantly decreased in the expression of IL-6, IL-1β, and TNF-α. In addition, compared to the CON group, the levels of synapse-related proteins including synapsin-1 and -2 were significantly reduced in the Cis-CON group, and there was a significant difference between the Cis-CON and Cis-EXE groups. Antioxidant and apoptosis factors were significantly improved in the Cis-EXE group compared with the Cis-CON group. This study suggest that exercise could be meaningful approach to prevent or improve cisplatin-induced cognitive impairment.

• The Korean Journal of Physiology and Pharmacology
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• 제25권6호
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• pp.585-592
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• 2021

Cisplatin has been reported to cause side effects such as muscle wasting in humans and rodents. The physiological mechanisms involved in preventing muscle wasting, such as the regulation of AKT, PGC1-α, and autophagy-related factor FOXO3a by MuRF 1 and Atrogin-1, remain unclear following different types of exercise and in various skeletal muscle types. Eight-week-old male Wistar rats (n = 34) were assigned to one of four groups: control (CON, n = 6), cisplatin injection (1 mg/kg) without exercise (CC, n = 8), cisplatin (1 mg/kg) + resistance exercise (CRE, n = 9) group, and cisplatin (1 mg/kg) + aerobic exercise (CAE, n = 11). The CRE group performed progressive ladder exercise (starting with 10% of body weight on a 1-m ladder with 2-cm-interval grids, at 85°) for 8 weeks. The CAE group exercised by treadmill running (20 m/min for 60 min daily, 4 times/week) for 8 weeks. Compared with the CC group, the levels of the autophagy-related factors BNIP3, Beclin 1, LC3-II/I ratio, p62, and FOXO3a in the gastrocnemius and soleus muscles were significantly decreased in the CRE and CAE groups. The CRE and CAE groups further showed significantly decreased MuRF 1 and Atrogin-1 levels and increased phosphorylation of AKT, FOXO3a, and PGC1-α. These results suggest that both ladder and aerobic exercise directly affected muscle wasting by modulating the AKT/PGC1-α/FOXO3a signaling pathways regardless of the skeletal muscle type.

• Korean Journal of Acupuncture
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• 제36권1호
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• pp.63-73
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• 2019

Objectives : This study was designed to investigate the effects of Alismatis Rhizoma (AR) pharmacopuncture at BL23 on acute renal failure induced by cisplatin. Methods : The Sprague-Dawley rats were divided into Normal group (no injection of cisplatin and no treatment), Control group (cisplatin injection without treatment), Acu group (needling at BL23 after cisplatin injection), AR-PA1 group (treated with $0.3571mg/kg/20{\mu}l$ of AR pharmacopuncture at BL23 after cisplatin injection), and AR-PA2 group (treated with $1.7855mg/kg/20{\mu}l$ of AR pharmacopuncture at BL23 after cisplatin injection). Each treatment was given once daily for 8 days. Changes in body weight, kidney weight, tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin-6 (IL-6), Cu-Zn superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GPx), serum blood urea nitrogen (serum BUN), and serum creatinine were observed. Results : Body weight was significantly increased in AR-PA1 on $4^{th}$ and $6^{th}$ days and AR-PA2 on $2^{nd}$ day. $TNF-{\alpha}$ was significantly decreased in Acu, AR-PA1 and AR-PA2 groups. Cu-Zn SOD was significantly increased in AR-PA2 group. GPx was significantly increased in AR-PA1 and AR-PA2 groups. But kidney weight, IL-6, serum BUN and serum creatinine were not significantly changed in any groups compared to control group. Conclusions : In acute renal failure induced by cisplatin, AR pharmacopuncture has a mitigating effect on the inflammatory reaction related to the increase of $TNF-{\alpha}$ in the kidney tissue and a protective effect on the oxidative stress of the kidney tissue. However it is unlikely to restore the glomerular function or inhibit the renal swelling.

• Radiation Oncology Journal
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• 제22권3호
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• pp.200-207
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• 2004

목적: 국소적으로 진행된 자궁경부암 치료에 있어 방사선 단독치료요법과 방사선 및 방사선 민감제로 저용량 Cisplatin으로 병용요법의 치료 성적을 후향적으로 분석하였다. 대상 및 방법: 1996년 12월부터 2001년 3월까지 근치적 방사선치료를 받은 59명의 국소적으로 진행된 자궁경부암 환자를 대상으로 생존율, 반응, 재발양상, 부작용에 대하여 후향적으로 분석을 하였다. 방사선 단독으로 치료한 환자는 31명이며, 저용량 cisplatin을 방사선치료와 병용치료한 환자는 28명이었다. 대상 환자의 추적조사 기간은 2.5개월에서 73개월로 중앙값은 34개월이었다. 방사선치료는 외부방사선치료로 골반강에 4,500 cGy와 자궁방결합조직에 900$\~$l,000 cGy를 추가로 치료하였고, Ir-192 고선량률 근접 치료기(micro-Selectron HDR)로 6$\~$7회 강내조사(point "A"에 3,000$\~$3,500 cGy, 500 cGy/fx, 주 2회)를 시행하였다. 병용치료 군에서는 방사선치료 첫날부터 20일째 되는 날까지 cisplatin 10 mg을 방사선치료 30분 전에 투여하였다 FIGO 병기별로 IIB가 51명(86.4$\%$), IIIB가 8명(13.6$\%$)이고, 조직병리상 54명(91.5$\%$)이 편평상피세포암, 2명(3.4$\%$)이 선암, 3명(5.1$\%$)이 편평상피선암이었다. 결과: 대상환자 59명에 대한 5년 생존율과 무병생존율은 각각 65.7$\%$와 55.8$\%$였다. 치료방법에 따른 결과로 방사선 단독치료군과 병용치료군에서 5년 생존율은 각각 56.8$\%$와 73.4$\%$ (p=0.180)였고, 무병 생존율은 각각 49.4$\%$와 63.3$\%$ (p=0.053)였다. 그리고 5년 국소제어율은 각각 52.3$\%$와 73.6$\%$ (p=0.013)였으며 , 5년 원격제어율은 각각 59.3$\%$와 81.5$\%$ (p=0.477)였다. 급성합병증 중에서 3등급 이상의 백혈구감소(3.2$\%$ vs 28.5$\%$, p=0.02)와, 3등급 이상의 혈소판감소(0$\%$ vs 7.1$\%$, p=0.04)만 병용치료군에서 통계적으로 증가되어 있었다. 만성합병증은 양 군 간에서 의미 있는 차이를 보이지 않았다. 결론: 본 연구 결과 방사선치료와 방사선 민감제로 저용량 Cisplatin의 병용치료방법은 방사선단독치료 방법에 비하여 무병생존율과 국소제어율에는 영항을 미쳤으나, 생존율을 향상시키지는 못했고, 급성독성으로 골수억제의 빈도가 더 높게 나타났다.

• 대한간호학회지
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• 제32권2호
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• pp.206-219
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• 2002

This study was conducted to investigate nutrient and food choices in gastric cancer patients receiving Cisplatin after surgery. Ten patients were followed from the fist day of the first cycle to the last date of the 6th the cycle of the chemotherapy. The subjects kept daily self record of dietary intake and the period of nausea/vomiting during 6 cycles. Using Computer Aided Nutritional Analysis Program, the degree of Calorie, carbohydrate, protein, fat and fluid intakes according the chemotherapy period. The reseacher developed food intake rating scale, and then three dietitians analysed the oral intakes according to the type of foods. As the results of this study, during the chemotherapy cancer patients are intakes much fewer calorie, protein and fluids than recommended dietary allowance. Oral intake was worsen as treatment proceed. During the chemotherapy periods most of the patients choose fruits, vegitables, steam rice, porridge, yogurt and the beam soup to overcome nausea and vomiting. In order to promote oral intake for chemotherapy patients, the researcher strongly suggest that indiviual food preform should be considered.