• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.517-520
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• 2012

Single original gemcitabine is commonly used as salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, efficacy data fro this regimen are limited. We therefore conducted a retrospective study to evaluate the outcome of patients who received single-agent generic gemcitabine (GEMITA) after development of clinical platinum resistance. The study period was between May 2008 and December 2010. Gemcitabine was administered intravenously in two different schedules: 1,000 $mg/m^2$ on day 1,8, and 15 every 28 days; and on days 1 and 8 every 21 days with the same dosage. Administration was until disease progression was noted. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while toxicity was evaluated according to WHO criteria. Sixty-six patients met the inclusion criteria in the study period. Two-thirds of them received gemcitabine as the second and third line regimen. The overall response rate was 12.1%. The median progression free survival and overall survival was 2 and 10 months, respectively. With the total 550 courses of chemotherapy,the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 1.5%; leukopenia, 13.7%; neutropenia, 27.3%; and thrombocytopenia, 3.0%. In conclusion, single agent generic gemcitabine revealed a modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2061-2067
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• 2014

Background: It has been demonstrated that neutrophil:lymphocyte (NLR) and platelet:lymphocyte (PLR) ratios are associated with prognosis in cancer patients. The aim of this study was to investigate whether pretreatment white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet, basophil and eosinophil counts, LDH level, NLR and PLR are associated with prognosis in patients with malignant pleural mesothelioma (MPM). Materials and Methods: We retrospectively reviewed files of 50 patients who were managed with a diagnosis of MPM between 2005 and 2010. Demographic and clinical characteristics, treatments, response to treatment and prognostic factors were evaluated, along with relationships between pretreatment blood parameters and prognosis. Results: Overall, 38 men and 12 women were included to the study. Mean age was $61.5{\pm}9.4$ years (range: 39-83 years). There was advanced disease in 86% (n=43) and the histological type was epithelial mesothelioma in the majority (82%). Of the cases, 17 (34%) received radiotherapy, while 42 cases underwent first- and second-line chemotherapy, with cisplatin plus pemetrexed as the most commonly used regimen. In the assessment after therapy, it was found that there was complete response in 4 cases (8%), partial response in 10 cases (20%), stable disease in 17 cases (34%) and progression in 19 cases (38%). Median follow-up was 10 months (range: 10 day-30 months). Median overall survival was found to be 20.7 months while median progression-free survival as 10 months. In univariate and multivariate analyses, it was found that factors significantly affecting overall survival included stage (p=0.030), response to treatment (p=0.026) and monocyte count (p=0.004), while factors affecting disease-free survival included NLR (p=0.018), response to treatment (p=0.001), and PLR score (p=0.003). Conclusions: Overall and disease-free survival was found to be better in cases with a WBC count<8.000, platelet count<300,000, and low NLR and PLR scores in malignant pleural mesothelioma.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1837-1840
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• 2012

Background: In spite of the fact that platinum-based doublets are considered the standard therapy for patients with advanced non-small-cell lung cancer (NSCLC), no elderly-specific platinum based prospective phase III regimen has been explored. The aim of this retrospective singlecenter study was to evaluate the efficacy and side effects of cisplatin-based therapy specifically for the elderly. Methods: Patients receiving platinum-based treatment were divided into three groups. In the first group (GC), Gemcitabine was administrated at 1000 $mg/m^2$ on days 1, 8 and cisplatin was added at 75 $mg/m^2$ on day 1. In the second group (DC), 75 $mg/m^2$ docetaxel and cisplatin were administered on day 1. The third group (PC) received 175 mg of paclitaxel and 75 mg of cisplatin on day 1. These treatments were repeated every three weeks. Result: GC arm had 36, the DC arm 42 and the PC arm 29 patients. Grade III-IV thrombocytopenia was higher in the GC arm (21.2% received GC, 2.8% received DC, and 3.8% received PC), while sensory neuropathy was lower in patients with GC arm (3.0%, 22.2%, and 23.1% received GC, DC and PC, respectively). There were no statistically significant difference in the response rates among the three groups (p>0.05). The median Progression-free survival (PFS) was 5.0 months and the median Overall survival (OS) in each group was 7.1, 7.4 and 7.1 months, respectively (p>0.05). Conclusion: The response rate, median PFS and OS were similar among the three treatment arms. Grade III-IV thrombocytopenia was higher in the GC arm, while the GC regimen was more favorable than the other cisplatin-based treatmetns with regard to sensory neuropathy.

• Tuberculosis and Respiratory Diseases
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• 제57권2호
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• pp.160-168
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• 2004

배 경 : 비소세포폐암에서 2차 항암화학요법에 대한 치료반응과 역할은 아직 정립되어 있지 못한 실정이다. 한편, 최근 개발된 ZD1839는 상피세포성장인자 수용체 억제제로서 악성 고형 종양, 특히 비소세포폐암에서 항종양효과를 보이는 것으로 알려져 있다. 저자들은 기존의 표준 항암화학요법에 실패한 진행성 비소세포폐암 환자들을 대상으로 ZD1839를 투여하여 그 반응 및 안전성을 평가하고자 하였다. 대상 및 방법 : 원자력병원에서 비소세포폐암으로 조직학적 진단을 받고 임상 병기 IIIB 이상인 환자들 중에서 1차 이상의 항암화학요법을 시행 받은 후 치료실패로 판정된 환자들을 대상으로 2002년 1월부터 2003년 9월까지 ZD1839를 투여 하였다. 투여 용량은 하루 250 mg이었고, 반응 및 부작용을 평가하기 위해 1개월 간격으로 흉부 방사선 검사 및 외래 추적 검사를 실시하였다. 이 환자들 중 반응 및 독성의 평가가 가능하였던, 1개월 이상 투여 받은 83명의 환자들을 대상으로 하였다. 환자들의 중앙 연령은 59(33-76)세였고, 임상 병기는 IIIB가 12명, IV가 71명이었으며, ECOG 전신수행상태는 0-1이 10명, 2는 42명, 3은 31명이었다. ZD1839 투여일수는 중앙값이 90일이었다. 결 과 : ZD1839 투여 후 부분 반응은 12명(14.5%), 불변은 31명(37.3%), 진행은 40명(48.2%)이었고, 전체 생존기간과 병의 진행까지 기간의 중앙값은 각각 9.2 개월과 3.1 개월이었다. ZD1839의 부작용으로는 피부 발진을 보인 환자가 25명(25.8%)으로 가장 많았으며, 구토 및 설사를 보인 환자가 15(15.5%), 비정상적 간효소수치 상승 및 혈소판 감소를 보인 환자가 각각 1명(1.03%)이었다. Performance status 0, 1인 전신 상태와 선암종을 가진 환자군에서 반응률 및 생존률이 통계적으로 유의한 증가를 보였다. 결 론 : 기존의 항암화학요법에 실패한 일부 진행성 비소세포폐암 환자들에서 ZD1839 투여는 비교적 높은 반응률을 보였으며 부작용은 비교적 경미하였다. 향후 보다 대규모의 연구 결과에 대한 추시가 필요할 것으로 생각된다.

• Journal of Digestive Cancer Research
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• 제1권1호
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• pp.36-42
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• 2013

배경 및 목적: Gemcitabine은 진행성 췌장암 환자의 치료에 우선적으로 사용되며, 다른 항암 약제에 비하여 상대적으로 독성이 적은 것으로 알려져 있다. 그러나 약제의 낮은 반응률과 상대적으로 높은 합병증의 발생률 때문에 많은 소화기암을 다루는 의사들은 췌장암을 가진 노인환자에서 항암치료를 꺼려하는 경항이 있다. 방법: 2007년에서 2010년 사이에 조직학적으로 췌장암을 진단받고, gemcitabine 항암요법을 시행받은 61명의 환자를 후향적으로 임상적, 검사실 및 영상학적 자료를 분석하였다. 환자는 65세 이상군 28명과 65세 미만군 38명으로 나누었다. Gemcitabine은 체표면적당 1,000 mg을 3주 동안 매주 30분에 걸쳐 투여하였고, 다른 항암제인 cisplatin, capecitabine, erlotinib 등을 병합 투여한 경우가 있었다. 결과: 환자의 평균 나이는 65세 이상군에서 71세, 65세 미만군에서 56세 였다. 진단 시 시행한 CA 19-9을 포함한 검사실검사는 두 군 간에 차이가 없었으며, gemcitabine 단독 항암요법을 시행한 경우는 65세 이상군에서 더 많았고(56.5 vs. 26.3%, p=0.029), 2차 혹은 3차 항암요법을 시행한 군은 65세 미만군에서 더 많았다(17.4 vs. 50.0%, p=0.014). 담관염이나 담관스텐트 유치는 양군에서 차이가 없었다. 결과: Gemcitabine 항암화학요법은 진행성 췌장암을 가진 노인환자에서 안전하게 사용할 수 있으며, 젊은 환자들에 견줄만한 치료 반응률과 무진행생존기간을 기대할 수 있을 것으로 예상된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3123-3128
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• 2014

The liver is normally the major site of glucose metabolism in intact organisms and the most important target organ for the action of insulin. It has been widely accepted that insulin resistance (IR) is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). However, the relationship between IR and drug resistance in liver cancer cells is unclear. In the present study, IR was induced in HepG2 cells via incubation with a high concentration of insulin. Once the insulin-resistant cell line was established, the stability of HepG2/IR cells was further tested via incubation in insulin-free medium for another 72h. Afterwards, the biological effects of insulin resistance on adhesion, migration, invasion and sensitivity to cis-platinum (DDP) of cells were determined. The results indicated that glucose consumption was reduced in insulin-resistant cells. In addition, the expression of the insulin receptor and glucose transportor-2 was downregulated. Furthermore, HepG2/IR cells displayed markedly enhanced adhesion, migration, and invasion. Most importantly, these cells exhibited a lower sensitivity to DDP. By contrast, HepG2/IR cells exhibited decreased adhesion and invasion after treatment with the insulin sensitizer pioglitazone hydrochloride. The results suggest that IR is closely related to drug resistance as well as adhesion, migration, and invasion in HepG2 cells. These findings may help explain the clinical observation of limited efficacy for chemotherapy on a background of IR, which promotes the invasion and migration of cancer cells.

• Tuberculosis and Respiratory Diseases
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• 제66권2호
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• pp.93-97
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• 2009

연구배경: Belotecan (Camtobell, CKD-602, Chongkundang Pharm., Korea)은 camptothecin의 치환체로 topoisomerase I 효소를 억제하여 항암효과를 나타내는 것으로 알려져 있다. 이에 2차 항암화학요법에 치료제로써 Belotecan 의 효과, 생존율 및 부작용에 대해 연구하였다. 방 법: 이에 소세포폐암에서 etoposide와 platinum을 사용한 1차 항암화학요법에서 실패한 49명의 환자들을 대상으로 2차 항암화학요법에 Belotecan을 투약하였다. 결 과: 전체 반응률은 25%였으며, 11명의 환자에서 partial response를 보였다. 또한 1차 항암화학요법 이후 90일 이내에 재발한 군과 90일 이상 경과한 군간에 유의한 차이는 보이지 않았다. 전체 환자의 중심생존기간은 10.3개월(290일)이었고, 비반응군에서는 186일(95% CI; 67-305)로 반응군의 471일(95% CI; 234-568)에 비해 생존기간의 감소 유의하게 있음을 확인하였다(p=0.07). 결 론: 2차 항암화학요법의 치료제로써 Belotecan의 효능과 부작용에 대해서는 향후 무작위 비교 연구가 필요할 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.131-134
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• 2016

Breast cancer is the most common malignancy and also the second leading cause of cancer death among women and also in women that have a high mortality. Previous studies showed that magnesium (Mg) has cytotoxic effects on malignant cell lines. However, the anti-cancer effects of Mg on MCF-7 breast cancer cells are uncertain. This study was aimed at the comparison of the cytotoxic effect of Mg salt (MgCl2) and cisplatin on MCF-7 cells and fibroblasts (as normal cells). After treatment with various concentrations of MgCl2, and cisplatin as a positive control for 24 and 48 hours (h), cytotoxicity activity was measured by MTT assay. In addition, apoptosis was determined by annexin V/propidium iide assay. Both cisplatin and the MgCl2 exhibited dose-dependent cytotoxic effects in the MCF-7 cell line, although the LD50 of the Mg was significantly higher when compared to cispaltin ($40{\mu}g/ml$ vs. $20{\mu}g/ml$). Regarding annexin V/propidium results, treatment of MCF-7 cells with LD50 concentrations of cisplatin and Mg showed 59% and 44% apoptosis at 24h, respectively. Finally, the results indicated that Mg has cytotoxic effects on MCF-7 cells, but less than cisplatin as a conventional chemotherapeutic agent. However, regarding the side effects of chemotherapy drugs, it seems that Mg can be considered as a supplement for the treatment of breast cancer.

• Journal of Gastric Cancer
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• 제17권2호
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• pp.132-144
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• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• Clinical and Experimental Pediatrics
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• 제51권1호
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• pp.78-83
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• 2008

목 적 : 골육종은 소아 청소년기에 뼈에 발생하는 가장 흔한 악성종양으로 종양 제거술 및 집중적 항암 화학요법을 시행한 경우에도 약 30-40%에서 재발하는 매우 침습적인 질환이다. 하지만 아직까지 재발한 골육종의 예후 및 예후인자에 대한 연구가 부족한 상태이다. 저자들은 치료 후 재발한 골육종 환아의 치료성적 및 재발 후 생존율에 영향을 주는 요인들을 분석하고자 하였다. 방 법 : 1985년 2월부터 2004년 2월까지 원자력병원에서 골육종으로 치료한 461명의 환아 중 재발한 180명의 의무기록을 후향적으로 조사하였으며 재발 후 생존율과 재발 후 예후인자로 재발병소의 위치, 재발 후 치료 방법, 원발병소의 수술전 화학요법에 대한 병리학적 반응도, 첫 진단 시 전이여부 및 재발기간을 분석하였다. 결 과 : 전체 재발율은 39%였고 재발한 골육종 환아의 5년 및 10년 재발 후 생존율은 각각 13%와 4%였다. 평균 재발기간은 15개월이었다. 재발 후 5년 생존율에 영향을 주는 인자는 재발 부위(폐, 39%; 원발병소, 0%; 폐와 뼈의 재발, 25%; 기타 부위의 재발, 12%), 병소 부위 절제 여부(절제한 경우 38%; 절제하지 않은 경우 11%), 재발기간(1년 이내에 재발한 경우 13%, 1년 이후에 재발한 경우 44%)이었다. 결 론 : 재발된 골육종 환자의 생존율은 높지 않다. 하지만 본 연구에서는 재발된 병변을 적극적으로 치료할 때 생존율이 향상됨을 보여주고 있으며 특히 재발기간이 길고 폐에 재발된 경우에는 수술 및 항암 화학요법과 그 외의 적극적인 치료가 필요하다 하겠다.