• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2771-2774
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• 2012

Aim: Tumors of upper gastrointestinal tract are among the cancers that have a quite lethal course. Cytotoxic chemotherapy is the most efficient therapeutic modality for metastatic gastric cancer. In patients who do not respond to first-line treatment, the response rate to second-line therapies is generally low and the toxicity rates high. This study concerned the efficacy and the side effect profile of second-line therapy with irinotecan in the patients who were being followed-up with the diagnosis of metastatic gastric cancer in $\dot{I}$zmir, Turkey. Materials and Methods: We retrospectively evaluated the efficacy and toxicity in 31 patients with metastatic gastric adenocarcinoma who presented to the polyclinic of Medical Oncology of Izmir Ataturk Education and Research Hospital between May 2008 and July 2011. All received chemotherapy regimens containing cisplatin, fluoropyrimidine (5-FU) and docetaxel as the first-line therapy for late stage disease. Irinotecan as a single agent was given at a dose of 210 mg/$m^2$ on each 21 days. Irinotecan (180 mg/$m^2$ on day 1), 5-FU (500 mg/$m^2$ on days 1-2) and leucovorin (LV; 60 mg/$m^2$ on days 1-2) as a combined regimen were given over a 14 day period. Results: Median age was 54 (range, 31-70). Irinotecan was given as a combined regimen for median 6 cycles (range, 3-12) and as a single agent for median 3 cycles (range, 1-10). Metastases were detected in one site in six patients (19%), in two different sites in 17 patients (55%) and in three or more sites in eight patients (26%). Four patients (12.9%) showed partial response and six patients (19.3%) showed stable disease. Progression-free survival (PFS) was found to be 3.26 months (95% CI, 2.3-4.2). Median overall survival (OS) was found to be 8.76 months (95% CI, 4.5-12.9). The most commonly seen grade 3/4 side effect was neutropenia but the the therapy was generally well-tolerated. Conclusions: In this study, it was demonstrated that second-line therapy with irinotecan given following the first-line therapy with cisplatin, fluoropyrimidine (5-FU) and docetaxel was efficient and safe. Further studies are needed for confirmation.

• Toxicological Research
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• 제33권3호
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• pp.255-263
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• 2017

Chemotherapy is associated with male infertility. Cisplatin (cis-diamminedichloro-platinum (II) (CDDP) as a chemotherapy medication used to treat a number of cancers has been reported to most likely induce testicular toxicity. Administration of antioxidants, such as pentoxifylline (PTX) may reduce some Adverse Drug Reactions (ADRs) of CDDP. Therefore, this study investigated the potentially protective effects of PTX on CDDP-induced testicular toxicity in adult male rats. For this purpose, 42 male rats were randomly divided into 7 groups. The rats were orally pretreated with PTX at the 3 doses of 75, 150, and 300 mg/kg once a day for 14 successive days. On the $14^{th}$ day of the study, they were intraperitoneally (IP) administered with a single dose of CDDP (7 mg/kg). Finally, the sperm/testis parameters, serum levels of reproductive hormones, including testosterone, Luteinizing Hormone (LH), and Follicle Stimulating Hormone (FSH) as the pivotal endocrine factors controlling testicular functions, and histopathological changes of testis tissue were examined. Pretreatment with the two doses of 75 and 150 mg/kg PTX indicated significant increases in the sperm count and motility induced by CDDP administration. The right and significantly left testis weights were decreased following the treatment with 300 mg/kg of PTX plus CDDP. However, 75 mg/kg of PTX plus CDDP showed the best near-to-normal histopathological features. The results demonstrated that PTX alone enhanced some parameters, such as the sperm count, while reducing other parameters, including sperm fast motility and germ layer thickness. Furthermore, despite testosterone or LH levels, the mean serum FSH level was significantly augmented by the doses of 75 and 150 mg/kg. It was concluded that PTX administration cannot reduce CDDP-induced testicular toxicity even at high doses (e.g., 300 mg/kg), while it seemed to partially intensify CDDP toxicity effects at a dose of 75 mg/kg. Thus, further research is required in this regard.

• 대한골관절종양학회지
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• 제1권1호
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• pp.17-22
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• 1995

From Sept. 1986 to Dec. 1992, seventy three cases of Enneking's stage IIB osteosarcoma of extremities, which were proved histologically, took neoadjuvant chemotherapy and completed our protocol. Their average age was 16.7 years(7 to 57). For neoadjuvant chemotherapy, 37 cases took high dose methotrexate(HDMTX)-adriamycin(ADR)-cisplatin(CDDP) regimen(HDMTX group) and 36 cases took ADR-CDDP(ADR-CDDP group). The average follow up was 17 months(2-63). According to Kaplan-Meier's plot, 5-year continuously disease free survival for whole 73 cases of neoadjuvant group was 45.2%, for HDMTX group 68.4%, for ADR-CDDP group 26.6%. There was significant stastical difference between these two groups(p<0.001), with log-rank test. There can be a different survival according to the chemotherapeutic protocols. Better results can be achieved through refined protocol and effective chemotherapeutic agents.

• 대한의생명과학회지
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• 제29권3호
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• pp.178-183
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• 2023

Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. Regulation of the cytotoxic activity of NK cells relies on integrated interactions between inhibitory receptors and numerous activating receptors that act in tandem to eliminate tumor cells efficiently. Conventional chemotherapy is designed to produce an anti-proliferative or cytotoxic effect on early tumor cell division. Therapies designed to kill cancer cells and simultaneously maintain host anti-tumor immunity are attractive strategies for controlling tumor growth. Depending on the drug and dose used, several chemotherapeutic agents cause DNA damage and cancer cell death through apoptosis, immunogenic cell death, or other forms of non-killing (i.e., mitotic catastrophe, senescence, autophagy). Among stress-induced immunostimulatory proteins, changes in the expression levels of NK cell activating and inhibitory ligands and tumor cell death receptors play an important role in the detection and elimination by innate immune effectors including NK cells. Therefore, we will address how these cytotoxic lymphocytes sense and respond to high and low concentrations of drug-induced stress to the drug cisplatin, among the various types of drugs that contribute to their anticancer activity.

• 대한약침학회지
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• 제19권2호
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• pp.114-121
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• 2016

Objectives: Lung cancer remains a deadly disease with unsatisfactory overall survival. Cisplatin, a standard platinum (Pt)-based chemotherapeutic agent, has the potential to inhibit the growth of lung cancer. Its use, however, is occasionally limited by severe organ toxicity. However, until now, no systematic study has been conducted to verify its efficacy with proper experimental support in vivo. Therefore, we examined whether biosynthesized Pt nanoparticles (NPs) inhibited human lung cancer in vitro and in vivo to validate their use in alternative and complementary medicine. Methods: We evaluated the in vitro and the in vivo anticancer efficiencies of biosynthesized Pt NPs in a subcutaneous xenograft model with A549 cells. Severe combined immune deficient mice (SCID) were divided into four groups: group 1 being the vehicle control group and groups 2, 3 and 4 being the experimental groups. Once the tumor volume had reached $70-75mm^3$, the progression profile of the tumor growth kinetics and the body weights of the mice were measured every week for 6 weeks after oral administration of Pt NPs. Doses of Pt NPs of 500, 1,000 and 2,000 mg/kg of body weight were administered to the experimental groups and a dose of honey was administered to the vehicle control group. The efficacy was quantified by using the delay in tumor growth following the administration of Pt NPs of A549 human-lung-cancer xenografts growing in SCID mice. Results: The in vitro cytotoxicity evaluation indicated that Pt NPs, in a dose-dependent manner, inhibited the growth of A549 cells, and the in vivo evaluation showed that Pt NPs at the mid and high doses effectively inhibited and delayed the growth of lung cancer in SCID mice. Conclusion: These findings confirm the antitumor properties of biosynthesized Pt NPs and suggest that they may be a cost-effective alternative for the treatment of patients with lung cancer.

• Radiation Oncology Journal
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• 제11권1호
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• pp.91-96
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• 1993

From September 1989 to June 1992,22 patients with nasopharyngeal carcinoma were treated in Asan Medical Center with an external beam of 60 Gy followed by a boost dose of 15 Gy HDR brachytherapy. There were 5 females and 17 males with median age of 44 years (range: 20-69 years). All patients were histologically confirmed and staged by physical examination, CT scan and/or MRI. By the AJCC TNM staging system, there were 2 patients with stge II (T2NO), 4 with stage III (T3NO, T1-3N1), and 16 with stage IV (T4 or N2-3). Four patients received chemotherapy with 5-FU and cisplatin prior to radiotherapy. All patients were followed up periodically by a telescopic examination and radiologic imaging study of CT scan or MRI with a median follow-up time of 13 months (range: 3-34 months). Twenty one patients showed a complete response ore month after completing therapy and one patient showed a complete response after three months. At the time of this analysis, seventeen patients remain alive without evidence of disease, but four patients developed distant metastasis and one patient died a month after treatment. The local control rate was $100{\%}$ in a median follow-up time of 13 months. The two year overall and disease free survival rates by the Kaplan-Meier method were $94{\%}$ and $67{\%}$, respectively. Serious radiation sequelae have not been observed yet. Although longer follow-up is needed, this retrospective analysis suggests that HDR brachytherap. given as a boost therapy for nasoharyngeal carcinoma may improve the local control. To reduce the incidence of distant metastasis, we need to develop a more effective systemic chemotherapy.

• Radiation Oncology Journal
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• 제20권1호
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• pp.62-67
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• 2002

목적 : 항문암의 치료에 있어 고전적으로는 복회음부절제술이 주된 치료였으나 현재는 화학방사선병용요법이 주된 치료방법으로 정립되었다. 저자들은 서울대학교병원에서 항문암으로 치료 받은 환자의 임상적 특성을 조사하고, 치료방법에 따른 치료성적과 예후인자를 분석하고자 하였다. 대상 및 방법 : 1979년 8월부터 1990년 7월까지 서울대학교병원 치료방사선과에서 근치적 또는 수술 후 방사선 치료를 받은 42명의 환자를 대상으로 후향적으로 분석하였다. 표피양암종이 38명으로 방사선치료가 4명에서, 복회음부절제술 및 수술 후 방사선치료${\pm}$화학요법이 19명에서, 화학방사선요법이 15명에서 시행되었다. 화학방사선요법은 복합화학요법$(5-FU\;1,000\;mg/m^2\;D1\~5,\;cisplatin\;60\;mg/m^2\;D1)$을 3회 시행 후 원발병소 및 영역림프절에 50.4 Gy를 조사하였고, 양측 서혜림프절에도 동일양을 조사하였다. 잔존암이 있는 경우 복합화학요법을 3회 추가 실시하였다. 중앙추적기간은 85개월이었다. 결과 : 전체 항문암 환자의 5년 생존율은 $80.3\%$이었다. 치료방법에 따른 5년 생존율은 복회음부절제술 및 수술 후 방사선치료${\pm}$화학요법군, 화학방사선요법군에서 각각 $88.9\%,\;79.4\%$이었으며 두군간의 생존율의 차이의 통계적인 의미는 없었다(p=0.495). 화학방사선요법을 시행 받은 환자군에서의 항문보존율은 $86.7\%$였다. 예후인자 중 단변량분석에서는 연령(p=0.0164)과 수행능력(p=0.0007)이 유의성을 보였으며, 다변량분석에서는 연령(p=0.0426)과 수행능력(p=0.0068) 및 서혜림프절 전이여부(p=0.0093)가 통계학적으로 유의하였다. 결론 : 항문암의 치료에 있어서 화학방사선요법을 시행할 경우 기존에 알려진 바와 같이 복회음부절제술과 유사한 생존율을 보이며, 항문기능을 보존할 수 있는 치료 방법임을 확인할 수 있었다. 나아가 병행화학요법이 아닌 선행화학요법을 시행하여 수반되는 합병증을 줄일 수 있는 가능성을 확인하였다.

• Radiation Oncology Journal
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• 제26권4호
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• pp.195-203
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• 2008

목 적: 절제 불가능한 식도암에서의 근치적 동시항암화학방사선치료의 치료 성적과 재발 양상에 대해 알아보고자하였다. 대상 및 방법: 1994년 2월부터 2002년 12월까지 서울아산병원에서 절제불가능한 국소진행된 식도암으로 진단 받거나 내과적으로 수술이 불가능한 식도암으로 진단 받은 후 근치적 목적의 동시항암화학방사선치료를 시행 받은 168명을 대상으로 하였다. 방사선치료는 원발병소와 종격동, 그리고 원발병소와 림프절 전이의 위치에 따라 쇄골상부림프절과 복강림프절을 포함하여 $42{\sim}46\;Gy$의 외부방사선을 조사하였고, 이후 원발병소와 림프절 전이 부위에는 $54{\sim}66\;Gy$까지 추가 조사하였다. 분할조사 방법은 분할조사선량 $1.8{\sim}2\;Gy$씩 1일 1회 조사하거나, 1.2 Gy씩 1일 2회 조사하였다. 고선량률관내 방사선치료를 실시하는 경우에는 Ir-192를 이용한 고선량률 방식으로 3 Gy씩 $3{\sim}4$회 시행하였다. 항암치료는 5-FU와 cisplatin을 이용하여 동시항암화학방사선치료(5-FU $1,00\;mg/m^2$/day, days $2{\sim}6$, $30{\sim}34$, cispiatin $60\;mg/m^2$/day, days 1, 29)를 2주기 시행하고 방사선치료 후에 2 주기를 추가하여 시행하였다. 결 과: 분석 가능한 환자는 160명 이었으며, 추적관찰 기간은 1개월에서 149개월(중앙값 10개월)이었다. 환자의 AJCC 병기는 I, II, III, IV 기가 각각 5명(3.1%), 38명(23.8%), 68명(42.5%), 49명(30.6%)이었다. 26명(16.3%)의 환자에서는 $9{\sim}12\;Gy$의 추가 관내방사선치료를 시행하였다. 관내방사선치료를 포함하여 총 40 Gy 이상 조사받은 144명의 환자에서 외부 방사선조사량의 범위는 $44.4{\sim}66\;Gy$ (중앙값 59.4)이었고, 총 방사선 조사량의 범위는 $44.4{\sim}72\;Gy$ (중앙값 60)이었다. 분석가능한 160명의 환자 중에서 101명(63.1%)에서 재발하였으며, 재발 양상으로는 국소 재발이 20명(12.5%), 지속적 병변 또는 국소 진행이 61명(38.1%), 원격전이가 15명(9.4%), 국소재발과 원격전이가 함께 있는 경우가 5명(3.)%)이었다. 전체환자의 중앙생존기간은 11.1개월이었고, 2년 및 5년 전체생존율은 각각 31.8%, 14.2%이었다. 중앙무병 생존기간은 10.4개월이었고, 2년 및 5년 무병생존율은 각각 29.0%, 22.7%이었다. 항암화학방사선치료 후에 종양 반응 및 림프절 병기만이 전체생존율에 유의하게 영향을 미치는 예후인자였다. 방사선 조사량(${\geq}50$ Gy vs. < 50 Gy), 관내 방사선치료의 추가 유무, 분할조사(1회/day vs. 2회/day)에 따른 전체 생존율 및 무병생존율에 유의한 차이는 관찰되지 않았다. 결 론: 식도암에서 근치적 동시 항암화학방사선치료의 성적은 다른 연구 결과와 유사한 결과를 보였다. 동시 항암화학 방사선치료 후의 주된 재발 양상은 국소 재발이었다. 방사선 조사량의 증가(${\geq}50\;Gy$), 고선량률관내방사선치료 및 과분할조사법의 시행은 치료 성적을 향상시키지 못하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9823-9829
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• 2014

Background: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). Objectives: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). Materials and Methods: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. Results: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan-Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were $43.4{\pm}6.0%$ and $53.2{\pm}6.1%$ respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [$69.8{\pm}10.5%$, $79.8{\pm}9.1%$ for MTX(+) and $31.1{\pm}6.9%$, $42.2{\pm}7.4%$ for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol ($66.7{\pm}13.6%$ and $15.0{\pm}8.0%$ for 3-year DFS, p=0.010, $73.3{\pm}13.2%$ and $20{\pm}8.9%$ for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). Conclusions: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.

• Radiation Oncology Journal
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• 제32권3호
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• pp.125-131
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• 2014

Purpose: We reviewed treatment outcomes and prognostic factors for patients with salivary ductal carcinoma (SDC) treated with surgery and postoperative radiotherapy from 2005 to 2012. Materials and Methods: A total of 16 patients were identified and 15 eligible patients were included in analysis. Median age was 61 years (range, 40 to 71 years) and 12 patients (80%) were men. Twelve patients (80%) had a tumor in the parotid gland, 9 (60%) had T3 or T4 disease, and 9 (60%) had positive nodal disease. All patients underwent surgery and postoperative radiotherapy. Postoperative radiotherapy was delivered using 3-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Locoregional failure-free survival (LRFFS), distant failure-free survival (DFFS), progression-free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Differences in survival based on risk factors were tested using a log-rank test. Results: Median total radiotherapy dose was 60 Gy (range, 52.5 to 63.6 Gy). Four patients received concurrent weekly chemotherapy with cisplatin. Among 10 patients who underwent surgery with neck dissection, 7 received modified radical neck dissection. With a median follow-up time of 38 months (range, 24 to 105 months), 4-year rates were 86% for LRFFS, 51% for DFFS, 46% for PFS, and 93% for OS. Local failure was observed in 2 patients (13%), and distant failure was observed in 7 (47%). The lung was the most common involved site of distant metastasis. Conclusion: Surgery and postoperative radiotherapy in SDC patients resulted in good local control, but high distant metastasis remained a major challenge.