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38 "Eun Kyung Cho"
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Original Articles
Lung and Thoracic cancer
Contribution of Enhanced Locoregional Control to Improved Overall Survival with Consolidative Durvalumab after Concurrent Chemoradiotherapy in Locally Advanced Non–Small Cell Lung Cancer: Insights from Real-World Data
Jeong Yun Jang, Si Yeol Song, Young Seob Shin, Ha Un Kim, Eun Kyung Choi, Sang-We Kim, Jae Cheol Lee, Dae Ho Lee, Chang-Min Choi, Shinkyo Yoon, Su Ssan Kim
Cancer Res Treat. 2024;56(3):785-794.   Published online January 16, 2024
DOI: https://doi.org/10.4143/crt.2023.1014
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to assess the real-world clinical outcomes of consolidative durvalumab in patients with unresectable locally advanced non–small cell lung cancer (LA-NSCLC) and to explore the role of radiotherapy in the era of immunotherapy.
Materials and Methods
This retrospective study assessed 171 patients with unresectable LA-NSCLC who underwent concurrent chemoradiotherapy (CCRT) with or without consolidative durvalumab at Asan Medical Center between May 2018 and May 2021. Primary outcomes included freedom from locoregional failure (FFLRF), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS).
Results
Durvalumab following CCRT demonstrated a prolonged median PFS of 20.9 months (p=0.048) and a 3-year FFLRF rate of 57.3% (p=0.008), compared to 13.7 months and 38.8%, respectively, with CCRT alone. Furthermore, the incidence of in-field recurrence was significantly greater in the CCRT-alone group compared to the durvalumab group (26.8% vs. 12.4%, p=0.027). While median OS was not reached with durvalumab, it was 35.4 months in patients receiving CCRT alone (p=0.010). Patients positive for programmed cell death ligand 1 (PD-L1) expression showed notably better outcomes, including FFLRF, DMFS, PFS, and OS. Adherence to PACIFIC trial eligibility criteria identified 100 patients (58.5%) as ineligible. The use of durvalumab demonstrated better survival regardless of eligibility criteria.
Conclusion
The use of durvalumab consolidation following CCRT significantly enhanced locoregional control and OS in patients with unresectable LA-NSCLC, especially in those with PD-L1–positive tumors, thereby validating the role of durvalumab in standard care.

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  • Therapeutic effect of induction therapy including nab-paclitaxel followed by surgical resection for the patients with locally advanced non-small-cell lung cancer
    Hidetaka Uramoto, Nozomu Motono, Shun Iwai
    Journal of Cardiothoracic Surgery.2024;[Epub]     CrossRef
  • 3,199 View
  • 151 Download
  • 1 Web of Science
  • 1 Crossref
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Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset
Ki Hyeong Lee, Byoung Chul Cho, Myung-Ju Ahn, Yun-Gyoo Lee, Youngjoo Lee, Jong-Seok Lee, Joo-Hang Kim, Young Joo Min, Gyeong-Won Lee, Sung Sook Lee, Kyung-Hee Lee, Yoon Ho Ko, Byoung Yong Shim, Sang-We Kim, Sang Won Shin, Jin-Hyuk Choi, Dong-Wan Kim, Eun Kyung Cho, Keon Uk Park, Jin-Soo Kim, Sang Hoon Chun, Jangyoung Wang, SeokYoung Choi, Jin Hyoung Kang
Cancer Res Treat. 2024;56(1):48-60.   Published online June 27, 2023
DOI: https://doi.org/10.4143/crt.2023.453
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC).
Materials and Methods
Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS).
Results
In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib.
Conclusion
Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Citations

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  • First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis
    Jietao Ma, Xiaoxue Pang, Shuling Zhang, Letian Huang, Li Sun, Chengbo Han
    Scientific Reports.2024;[Epub]     CrossRef
  • 6,040 View
  • 576 Download
  • 1 Web of Science
  • 1 Crossref
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Clinical Outcome of Stereotactic Body Radiotherapy in Patients with Early-Stage Lung Cancer with Ground-Glass Opacity Predominant Lesions: A Single Institution Experience
Jeong Yun Jang, Su Ssan Kim, Si Yeol Song, Young Seob Shin, Sei Won Lee, Wonjun Ji, Chang-Min Choi, Eun Kyung Choi
Cancer Res Treat. 2023;55(4):1181-1189.   Published online March 21, 2023
DOI: https://doi.org/10.4143/crt.2022.1656
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The detection rate of early-stage lung cancer with ground-glass opacity (GGO) has increased, and stereotactic body radiotherapy (SBRT) has been suggested as an alternative to surgery in inoperable patients. However, reports on treatment results are limited. Therefore, we performed a retrospective study to investigate the clinical outcome after SBRT in patients with early-stage lung cancer with GGO-predominant tumor lesions at a single institution.
Materials and Methods
This study included 89 patients with 99 lesions who were treated with SBRT for lung cancer with GGO-predominant lesions that had a consolidation-to-tumor ratio of ≤0.5 at Asan Medical Center between July 2016 and July 2021. A median total dose of 56.0 Gy (range, 48.0–60.0) was delivered using 10.0–15.0 Gy per fraction.
Results
The overall follow-up period for the study was median 33.0 months (range, 9.9 to 65.9 months). There was 100% local control with no recurrences in any of the 99 treated lesions. Three patients had regional recurrences outside of the radiation field, and three had distant metastasis. The 1-year, 3-year, and 5-year overall survival rates were 100.0%, 91.6%, and 82.8%, respectively. Univariate analysis revealed that advanced age and a low level of diffusing capacity of the lungs for carbon monoxide were significantly associated with overall survival. There were no patients with grade ≥3 toxicity.
Conclusion
SBRT is a safe and effective treatment for patients with GGO-predominant lung cancer lesions and is likely to be considered as an alternative to surgery.

Citations

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  • Recent Advancements in Minimally Invasive Surgery for Early Stage Non-Small Cell Lung Cancer: A Narrative Review
    Jibran Ahmad Khan, Ibrahem Albalkhi, Sarah Garatli, Marcello Migliore
    Journal of Clinical Medicine.2024; 13(11): 3354.     CrossRef
  • The clinical effect of thoracoscopic segmentectomy in the treatment of lung malignancies less than 2CM in diameter
    Yafeng Zhang, Renzhong Shi, Xiaoming Xia, Kaiyao Zhang
    Journal of Cardiothoracic Surgery.2024;[Epub]     CrossRef
  • Impact of ground-glass component on prognosis in early-stage lung cancer treated with stereotactic body radiotherapy via Helical Tomotherapy
    Jintao Ma, Shaonan Fan, Wenhan Huang, Xiaohong Xu, Yong Hu, Jian He
    Radiation Oncology.2024;[Epub]     CrossRef
  • 3,881 View
  • 224 Download
  • 5 Web of Science
  • 3 Crossref
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Integrin αvβ3 Induces HSP90 Inhibitor Resistance via FAK Activation in KRAS-Mutant Non-Small Cell Lung Cancer
Shinkyo Yoon, Hannah Yang, Hyun-Min Ryu, Eunjin Lee, Yujin Jo, Seyoung Seo, Deokhoon Kim, Chang Hoon Lee, Wanlim Kim, Kyung Hae Jung, Sook Ryun Park, Eun Kyung Choi, Sang-We Kim, Kang-Seo Park, Dae Ho Lee
Cancer Res Treat. 2022;54(3):767-781.   Published online September 30, 2021
DOI: https://doi.org/10.4143/crt.2021.651
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Heat shock protein-90 (HSP90) remains an important cancer target because of its involvement in multiple oncogenic protein pathways and biologic processes. Although many HSP90 inhibitors have been tested in the treatment of KRAS-mutant non–small cell lung cancer (NSCLC), most, including AUY922, have failed due to toxic effects and resistance generation, even though a modest efficacy has been observed for these drugs in clinical trials. In our present study, we investigated the novel mechanism of resistance to AUY922 to explore possible avenues of overcoming and want to provide some insights that may assist with the future development of successful next-generation HSP90 inhibitors.
Materials and Methods
We established two AUY922-resistant KRAS-mutated NSCLC cells and conducted RNA sequencing to identify novel resistance biomarker.
Results
We identified novel two resistance biomarkers. We observed that both integrin Av (ITGAv) and β3 (ITGB3) induce AUY922-resistance via focal adhesion kinase (FAK) activation, as well as an epithelial-mesenchymal transition, in both in vitro and in vivo xenograft model. mRNAs of both ITGAv and ITGB3 were also found to be elevated in a patient who had shown acquired resistance in a clinical trial of AUY922. ITGAv was induced by miR-142 downregulation, and ITGB3 was increased by miR-150 downregulation during the development of AUY922-resistance. Therefore, miR-150 and miR-142 overexpression effectively inhibited ITGAvB3-dependent FAK activation, restoring sensitivity to AUY922.
Conclusion
The synergistic co-targeting of FAK and HSP90 attenuated the growth of ITGAvB3-induced AUY922-resistant KRAS-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome acquired AUY922-resistance in KRAS-mutant NSCLC.

Citations

Citations to this article as recorded by  
  • Integrin αV Inhibition by GMI, a Ganoderma Microsporum Immunomodulatory Protein, Abolish Stemness and Migration in EGFR‐Mutated Lung Cancer Cells Resistant to Osimertinib
    Yu‐Ting Kang, Hui‐Yi Chang, Ya‐Chu Hsieh, Chia‐Hsuan Chou, I‐Lun Hsin, Jiunn‐Liang Ko
    Environmental Toxicology.2024; 39(12): 5238.     CrossRef
  • Junctional adhesion molecular 3 (JAM3) is a novel tumor suppressor and improves the prognosis in breast cancer brain metastases via the TGF-β/Smad signal pathway
    Kaitao Zhu, Shiwei Li, Hongru Yao, Jilong Hei, WenGuo Jiang, Tracey Martin, Shanyi Zhang
    Journal of Neuro-Oncology.2024; 170(2): 331.     CrossRef
  • Autophagy, molecular chaperones, and unfolded protein response as promoters of tumor recurrence
    Bashar Alhasan, Marina Mikeladze, Irina Guzhova, Boris Margulis
    Cancer and Metastasis Reviews.2023; 42(1): 217.     CrossRef
  • 8,821 View
  • 274 Download
  • 2 Web of Science
  • 3 Crossref
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Lung cancer
Real-World Experience of Nivolumab in Non-small Cell Lung Cancer in Korea
Sun Min Lim, Sang-We Kim, Byoung Chul Cho, Jin Hyung Kang, Myung-Ju Ahn, Dong-Wan Kim, Young-Chul Kim, Jin Soo Lee, Jong-Seok Lee, Sung Yong Lee, Keon Uk Park, Ho Jung An, Eun Kyung Cho, Tae Won Jang, Bong-Seog Kim, Joo-Hang Kim, Sung Sook Lee, Im-II Na, Seung Soo Yoo, Ki Hyeong Lee
Cancer Res Treat. 2020;52(4):1112-1119.   Published online May 15, 2020
DOI: https://doi.org/10.4143/crt.2020.245
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program.
Materials and Methods
Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected.
Results
Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data.
Conclusion
This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

Citations

Citations to this article as recorded by  
  • Advances in reprogramming of energy metabolism in tumor T cells
    Liu Xuekai, Song Yan, Chu Jian, Song Yifei, Wu Xinyue, Zhang Wenyuan, Han Shuwen, Yang Xi
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • Effectiveness and Safety of PD-1 Inhibitors’ Treatment for Patients with Non-Small-Cell Lung Cancer in China: A Real-World Study
    Ning Wan, Yongbang Chen, Liqing Lu, Bing Wang, Liuliu He, Hongyi Liang, Fei Xie, Xiaoshun Jian, Bo Ji, Jianping Zhang, Hammoda Abu-Odah
    European Journal of Cancer Care.2024; 2024: 1.     CrossRef
  • Optimization of treatment strategies for elderly patients with advanced non-small cell lung cancer
    Qiang Chen, Shuo Ying, Jianwen Qin, Li Zhang
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Real-World Data on Pembrolizumab for Pretreated Non-Small-Cell Lung Cancer: Clinical Outcome and Relevance of the Lung Immune Prognostic Index
    Ana Ortega-Franco, Clare Hodgson, Haseem Raja, Mathew Carter, Colin Lindsay, Sarah Hughes, Laura Cove-Smith, Paul Taylor, Yvonne Summers, Fiona Blackhall, Raffaele Califano
    Targeted Oncology.2022; 17(4): 453.     CrossRef
  • Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis
    Handai Xia, Wengang Zhang, Yuqing Zhang, Xiaoling Shang, Yanguo Liu, Xiuwen Wang
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Immune-Related Adverse Events Predict the Efficacy of Immune Checkpoint Inhibitors in Lung Cancer Patients: A Meta-Analysis
    Donghui Wang, Cen Chen, Yanli Gu, Wanjun Lu, Ping Zhan, Hongbing Liu, Tangfeng Lv, Yong Song, Fang Zhang
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Broad-Spectrum Antibiotic Regimen Affects Survival in Patients Receiving Nivolumab for Non-Small Cell Lung Cancer
    Min Jung Geum, Chungsoo Kim, Ji Eun Kang, Jae Hee Choi, Jae Song Kim, Eun Sun Son, Sun Min Lim, Sandy Jeong Rhie
    Pharmaceuticals.2021; 14(5): 445.     CrossRef
  • Nivolumab

    Reactions Weekly.2021; 1855(1): 269.     CrossRef
  • Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis
    Zhe Zhao, Xinfeng Wang, Jinghan Qu, Wei Zuo, Yan Tang, Huijuan Zhu, Xiaoguang Chen
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • 10,556 View
  • 308 Download
  • 15 Web of Science
  • 9 Crossref
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Axillary Lymph Node Dissection Does Not Improve Post-mastectomy Overall or Disease-Free Survival among Breast Cancer Patients with 1-3 Positive Nodes
Ji Hyeon Joo, Su Ssan Kim, Byung Ho Son, Seung Do Ahn, Jin Hong Jung, Eun Kyung Choi, Sei Hyun Ahn, Jong Won Lee, Hee Jeong Kim, Beom Seok Ko
Cancer Res Treat. 2019;51(3):1011-1021.   Published online October 16, 2018
DOI: https://doi.org/10.4143/crt.2018.438
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Axillary lymph node dissection (ALND) may be avoidable for breast cancer patients with 1-2 positive lymph nodes (LN) after breast-conserving therapy. However, the effects of ALND after mastectomy remain unclear because radiation is not routinely used. Herein, we compared the benefits of post-mastectomy ALND versus sentinel node biopsy (SNB) alone for breast cancer patients with 1-3 metastatic LNs.
Materials and Methods
A total of 1,697 patients with pN1 disease who underwent mastectomy during 2000-2015 were identified from an institutional database. Outcomes were compared using the inverse probability of treatment weighted method.
Results
Patients who underwent SNB tended to have smaller tumors, a lower histology grade, a lower number of positive LNs, and better immunohistochemical findings. After correcting all confounding factors regarding patient, tumor, and adjuvant treatment, the SNB and ALND groups did not differ in terms of overall survival (OS) and disease-free survival (DFS), distant metastasis and locoregional recurrence. The 10-year DFS and OS rates were 83% and 84%, respectively, during a median follow-up period of 93 months.
Conclusion
ALND did not improve post-mastectomy survival outcomes among patients with N1 breast cancer, even after adjusting for all histopathologic and treatment-related factors.

Citations

Citations to this article as recorded by  
  • The Impact of Sentinel Lymph Node Biopsy on Female Patients With T3-4c Breast Cancer and 1-2 Positive Lymph Nodes: A Population-Based Cohort Study
    Hanzhao Yang, Yadong Sun, Peili Wang, Jianghua Qiao, Chengzheng Wang, Zhenzhen Liu
    Clinical Breast Cancer.2024; 24(3): e126.     CrossRef
  • Axillary management in patients with clinical node-negative early breast cancer and positive sentinel lymph node: a systematic review and meta-analysis
    Changzai Li, Pan Zhang, Jie Lv, Wei Dong, Baoshan Hu, Jinji Zhang, Hongcheng Zhu
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Reevaluating Axillary Lymph Node Dissection in Total Mastectomy for Low Axillary Burden Breast Cancer: Insights from a Meta-Analysis including the SINODAR-ONE Trial
    Munaser Alamoodi, Neill Patani, Kinan Mokbel, Umar Wazir, Kefah Mokbel
    Cancers.2024; 16(4): 742.     CrossRef
  • RecurIndex-Guided postoperative radiotherapy with or without Avoidance of Irradiation of regional Nodes in 1–3 node-positive breast cancer (RIGAIN): a study protocol for a multicentre, open-label, randomised controlled prospective, phase III trial
    Jing Liu, Yuting Tan, Zhuofei Bi, Suning Huang, Na Zhang, An-du Zhang, Lina Zhao, Yu Wang, Zibin Liang, Yu Hou, Xiangying Xu, Jianying Chen, Fei Wang, Xiaowen Lan, Xiao Lin, Xiaoxue Zhang, Wenyi Zhou, Xuting Ye, Jian-gui Guo, Xiaohong Wang, Ran Ding, Jiay
    BMJ Open.2024; 14(7): e078049.     CrossRef
  • The prognostic analysis of further axillary dissection in breast cancer with 1-2 positive sentinel lymph nodes undergoing mastectomy
    Xueyi Zhao, Liu Yang, Congbo Cao, Zhenchuan Song
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer patients undergoing mastectomy
    Damiano GENTILE, Corrado TINTERRI
    Minerva Surgery.2024;[Epub]     CrossRef
  • Can Axillary Lymph Node Dissection be Omitted in Breast Cancer Patients with Metastatic Sentinel Lymph Nodes Undergoing Mastectomy? A Systematic Review and Meta‐Analysis of Real‐World Evidence
    Fulong Chen, Xiaowen Li, Xianjun Lin, Lijia Chen, Zhaoling Lin, Hao Wu, Jishang Chen
    World Journal of Surgery.2023; 47(10): 2446.     CrossRef
  • De-implementation of Axillary Dissection in Women Undergoing Mastectomy for Breast Cancer
    Laura D. Leonard, Thiago B. de Araujo, Christopher Quinn, Madeline B. Thomas, Laurel Beaty, Nicole M. Mott, Kathryn Colborn, Alicia A. Heelan, Sarah E. A. Tevis, Nicole Christian, Gretchen Arhendt, Ana L. Gleisner
    Annals of Surgical Oncology.2023; 30(9): 5692.     CrossRef
  • A multi-dimensional nomogram to predict non-sentinel lymph node metastases in T1–2HR+ breast cancer
    Ke Xiang, Jialin Chen, Yu Min, Hang Chen, Jiaxin Yang, Daixing Hu, Yuling Han, Guobing Yin, Yang Feng
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer patients undergoing mastectomy with one to two metastatic sentinel lymph nodes: sub-analysis of the SINODAR-ONE multicentre randomized clinical trial and reopening of enrolm
    Corrado Tinterri, Giuseppe Canavese, Wolfgang Gatzemeier, Erika Barbieri, Alberto Bottini, Andrea Sagona, Giulia Caraceni, Alberto Testori, Simone Di Maria Grimaldi, Carla Dani, Luca Boni, Paolo Bruzzi, Bethania Fernandes, Marta Scorsetti, Alberto Zambell
    British Journal of Surgery.2023; 110(9): 1143.     CrossRef
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    Yu-Jia Fan, Jin-Cheng Li, De-Miao Zhu, Hai-Long Zhu, Yi Zhao, Xin-Bing Zhu, Gang Wu, Ting-ting Bai
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    Mariana Peyroteo, Rita Canotilho, Ana Margarida Correia, Catarina Baía, Cátia Ribeiro, Paulo Reis, Abreu de Sousa
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    Olga Kantor, Jessica Means, Samantha Grossmith, Tanujit Dey, Jennifer R. Bellon, Elizabeth A. Mittendorf, Tari A. King
    Annals of Surgical Oncology.2022; 29(2): 972.     CrossRef
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    Mariana Peyroteo, Rita Canotilho, Ana Margarida Correia, Catarina Baía, Cátia Ribeiro, Paulo Reis, Abreu de Sousa
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    André Hennigs, Fabian Riedel, Manuel Feißt, Melitta Köpke, Mahdi Rezai, Ulrike Nitz, Mareike Moderow, Michael Golatta, Christof Sohn, Jörg Heil
    Annals of Surgical Oncology.2019; 26(8): 2435.     CrossRef
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  • 18 Web of Science
  • 19 Crossref
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A Randomized, Open-Label, Phase II Study Comparing Pemetrexed Plus Cisplatin Followed by Maintenance Pemetrexed versus Pemetrexed Alone in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Non-small Cell Lung Cancer after Failure of First-Line EGFR Tyrosine Kinase Inhibitor: KCSG-LU12-13
Kwai Han Yoo, Su Jin Lee, Jinhyun Cho, Ki Hyeong Lee, Keon Uk Park, Ki Hwan Kim, Eun Kyung Cho, Yoon Hee Choi, Hye Ryun Kim, Hoon-Gu Kim, Heui June Ahn, Ha Yeon Lee, Hwan Jung Yun, Jin-Hyoung Kang, Jaeheon Jeong, Moon Young Choi, Sin-Ho Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2019;51(2):718-726.   Published online September 3, 2018
DOI: https://doi.org/10.4143/crt.2018.324
AbstractAbstract PDFPubReaderePub
Purpose
The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).
Materials and Methods
We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles.
Results
A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms.
Conclusion
The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.

Citations

Citations to this article as recorded by  
  • The Survival and Financial Benefit of Investigator-Initiated Trials Conducted by Korean Cancer Study Group
    Bum Jun Kim, Chi Hoon Maeng, Bhumsuk Keam, Young-Hyuck Im, Jungsil Ro, Kyung Hae Jung, Seock-Ah Im, Tae Won Kim, Jae Lyun Lee, Dae Seog Heo, Sang-We Kim, Keunchil Park, Myung-Ju Ahn, Byoung Chul Cho, Hoon-Kyo Kim, Yoon-Koo Kang, Jae Yong Cho, Hwan Jung Yu
    Cancer Research and Treatment.2025; 57(1): 39.     CrossRef
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    New England Journal of Medicine.2024; 390(5): 478.     CrossRef
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    Balazs Halmos, Pragya Rai, Jae Min, Xiaohan Hu, Diana Chirovsky, Mark Shamoun, Bin Zhao
    Frontiers in Oncology.2024;[Epub]     CrossRef
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Efficacy and Safety of First-Line Necitumumab Plus Gemcitabine and Cisplatin Versus Gemcitabine and Cisplatin in East Asian Patients with Stage IV Squamous Non-small Cell Lung Cancer: A Subgroup Analysis of the Phase 3, Open-Label, Randomized SQUIRE Study
Keunchil Park, Eun Kyung Cho, Maximino Bello, Myung-Ju Ahn, Sumitra Thongprasert, Eun-Kee Song, Victoria Soldatenkova, Henrik Depenbrock, Tarun Puri, Mauro Orlando
Cancer Res Treat. 2017;49(4):937-946.   Published online January 6, 2017
DOI: https://doi.org/10.4143/crt.2016.423
AbstractAbstract PDFPubReaderePub
Purpose
The phase 3 randomized SQUIRE study revealed significantly longer overall survival (OS) and progression-free survival (PFS) for necitumumab plus gemcitabine and cisplatin (neci+GC) than for gemcitabine and cisplatin alone (GC) in 1,093 patients with previously untreated advanced squamous non-small cell lung cancer (NSCLC). This post hoc subgroup analysis assessed the efficacy and safety of neci+GC among East Asian (EA) patients enrolled in the study.
Materials and Methods
All patients received up to six 3-week cycles of gemcitabine (days 1 and 8, 1,250 mg/m²) and cisplatin (day 1, 75 mg/m²). Patients in the neci+GC arm also received necitumumab (days 1 and 8, 800 mg) until disease progression or unacceptable toxicity. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from stratified Cox proportional hazards models.
Results
In EA patients, there were improvements for neci+GC (n=43) versus GC (n=41) in OS (HR, 0.805; 95% CI, 0.484 to 1.341) and PFS (HR, 0.720; 95% CI, 0.439 to 1.180), consistent with the results for non-EA patients observed in the present study. The overall safety data were consistent between EA and non-EA patients. A numerically higher proportion of patients experienced serious adverse events (AEs), grade ≥ 3 AEs, and AEs with an outcome of death for neci+GC versus GC in EA patients and EA patients versus non-EA patients for neci+GC.
Conclusion
Although limited by the small sample size and post hoc nature of the analysis, these findings are consistent with those of the overall study and suggest that neci+GC offers a survival advantage and favorable benefit/risk for EA patients with advanced squamous NSCLC.

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An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer
In Hae Park, Joo Hyuk Sohn, Sung Bae Kim, Keun Seok Lee, Joo Seop Chung, Soo Hyeon Lee, Tae You Kim, Kyung Hae Jung, Eun Kyung Cho, Yang Soo Kim, Hong Suk Song, Jae Hong Seo, Hun Mo Ryoo, Sun Ah Lee, So Young Yoon, Chul Soo Kim, Yong Tai Kim, Si Young Kim, Mi Ryung Jin, Jungsil Ro
Cancer Res Treat. 2017;49(3):569-577.   Published online September 12, 2016
DOI: https://doi.org/10.4143/crt.2016.289
AbstractAbstract PDFPubReaderePub
Purpose
Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol).
Materials and Methods
Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 intravenously every 3 weeks. The primary outcome was the objective response rate (ORR).
Results
The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m2 (95.0%), and that of Genexol was 168.3±10.6 mg/m2 (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (pnon-inferiority=0.021, psuperiority=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments.
Conclusion
Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

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    Acta Pharmacologica Sinica.2017; 38(6): 931.     CrossRef
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Feasibility and Efficacy of Eribulin Mesilate in Korean Patients with Metastatic Breast Cancer: Korean Multi-center Phase IV Clinical Study Results
Yeon Hee Park, Tae Yong Kim, Young-Hyuck Im, Keun-Seok Lee, In Hae Park, Joohyuk Sohn, Soo-Hyeon Lee, Seock-Ah Im, Jee Hyun Kim, Se Hyun Kim, Soo Jung Lee, Su-Jin Koh, Ki Hyeong Lee, Yoon Ji Choi, Eun Kyung Cho, Suee Lee, Seok Yun Kang, Jae Hong Seo, Sung-Bae Kim, Kyung Hae Jung
Cancer Res Treat. 2017;49(2):423-429.   Published online August 3, 2016
DOI: https://doi.org/10.4143/crt.2016.191
AbstractAbstract PDFPubReaderePub
Purpose
Eribulin mesilate was approved for the treatment of patients with locally advanced or metastatic breast cancer (MBC),who had received at least two chemotherapeutic regimens, including anthracycline and taxane. On the other hand, the efficacy and safety information of eribulin in Korean patients is limited by the lack of clinical trials.
Materials and Methods
In this multicenter, open-label, single-arm, phase IV study, locally advanced or MBC patients were enrolled between June 2013 and April 2014 from 14 centers in Korea. One point four mg/m2 dose of eribulin was administered on days 1 and 8 of every 21 days. The primary endpoint was the frequency and intensity of the treatment emergent adverse event. The secondary endpoint was the disease control rate, which included the rate of complete responses, partial responses, and stable disease.
Results
A total of 101 patients received at least one dose of eribulin and were included in the safety set. The patients received a total of 543 treatment cycles, with a median of three cycles (range, 1 to 31 cycles). The most common adverse event was neutropenia (91.1% of patients, 48.3% of cycles). The frequent non-hematological adverse events included alopecia, decrease in appetite, fatigue/asthenia, and myalgia/arthralgia. The peripheral neuropathy of any grade occurred in 27 patients (26.7%), including grade 3 in two patients. Disease control rate was 52.7% and 51.3% of patients in the full analysis set and per-protocol set, respectively.
Conclusion
This study demonstrated the feasible safety profile and activity of eribulin in Korean patients with MBC.

Citations

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Prognostic Factors for Risk Stratification of Patients with Recurrent or Metastatic Pancreatic Adenocarcinoma Who Were Treated with Gemcitabine-Based Chemotherapy
Inkeun Park, Seung Joon Choi, Young Saing Kim, Hee Kyung Ahn, Junshik Hong, Sun Jin Sym, Jinny Park, Eun Kyung Cho, Jae Hoon Lee, Yong Ju Shin, Dong Bok Shin
Cancer Res Treat. 2016;48(4):1264-1273.   Published online March 23, 2016
DOI: https://doi.org/10.4143/crt.2015.250
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study was to verify prognostic factors including sarcopenia in patients with recurrent or metastatic pancreatic cancer receiving gemcitabine-based chemotherapy. Materials and Methods Medical records and computed tomography scan of consecutive patients treated with palliative gemcitabine-based chemotherapy from 2008 to 2014 were reviewed. The lumbar skeletal muscle index at third lumbar spine level was computed, and together with clinicolaboratory factors, univariate and multivariable analyses for overall survival (OS) were performed.
Results
A total of 88 patients were found. Median age was 65 years, and male patients were predominant (67.0%). Most patients had initially metastatic disease (72.7%), and gemcitabine monotherapy was administered in 29 patients (33.0%) while gemcitabine plus erlotinib was administered in 59 patients (67.0%). Seventy-six patients (86.3%) had sarcopenia. With a median follow-up period of 44.3 months (range, 0.6 to 44.3 months), median OS was 5.35 months (95% confidence interval [CI], 4.11 to 6.59). In univariate and multivariable analysis, high carcinoembryonic antigen level (hazard ratio [HR], 4.18; 95% CI, 1.95 to 8.97; p < 0.001), initially metastatic disease (HR, 3.37; 95% CI, 1.55 to 7.32; p=0.002), sarcopenia (HR, 2.97; 95% CI, 1.20 to 7.36; p=0.019), neutrophilia (HR, 2.94; 95% CI, 1.27 to 6.79; p=0.012), and high lactate dehydrogenase level (HR, 1.96; 95% CI, 1.07 to 3.58; p=0.029) were identified as independent prognostic factors for OS. Conclusion Five independent prognostic factors in patients with recurrent or metastatic pancreatic cancer who received gemcitabine-based chemotherapy were identified. These findings may be helpful in prediction of prognosis in clinical practice and can be used as a stratification factor for clinical trials.

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East Asian Subgroup Analysis of a Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-small Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL)
Keunchil Park, Joo-Hang Kim, Eun Kyung Cho, Jin-Hyoung Kang, Jin-Yuan Shih, Annamaria Hayden Zimmermann, Pablo Lee, Ekaterine Alexandris, Tarun Puri, Mauro Orlando
Cancer Res Treat. 2016;48(4):1177-1186.   Published online February 22, 2016
DOI: https://doi.org/10.4143/crt.2015.401
AbstractAbstract PDFPubReaderePub
Purpose
REVEL demonstrated improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) with docetaxel+ramucirumab versus docetaxel+placebo in 1,253 intent-to-treat (ITT) stage IV non-small cell lung cancer patients with disease progression following platinum-based chemotherapy. Results from the East Asian subgroup analysis are reported.
Materials and Methods
Subgroup analyses were performed in the East Asian ITT population (n=89). Kaplan-Meier analysis and Cox proportional hazards regression were performed for OS and PFS, and the Cochran-Mantel-Haenszel test was performed for response rate.
Results
In docetaxel+ramucirumab (n=43) versus docetaxel+placebo (n=46), median OS was 15.44 months versus 10.17 months (hazard ratio [HR], 0.762; 95% confidence interval [CI], 0.444 to 1.307), median PFS was 4.88 months versus 2.79 months (HR, 0.658; 95% CI, 0.408 to 1.060), and ORR was 25.6% (95% CI, 13.5 to 41.2) versus 8.7% (95% CI, 2.4 to 20.8). Due to increased incidence of neutropenia and febrile neutropenia in East Asian patients, starting dose of docetaxel was reduced for newly enrolled East Asian patients (75 to 60 mg/m2, n=24). In docetaxel+ramucirumab versus docetaxel+placebo, incidence of neutropenia was 84.4% versus 72.7% (75 mg/m2) and 54.5% versus 38.5% (60 mg/m2). Incidence of febrile neutropenia was 43.8% versus 12.1% (75 mg/m2) and 0% versus 7.7% (60 mg/m2).
Conclusion

Results
of this subgroup analysis showed a trend favoring ramucirumab+docetaxel for median OS, PFS, and improved ORR in East Asian patients, consistent with ITT population results. Reduction of starting dose of docetaxel in East Asian patients was associated with improved safety.

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Clinical Practices and Outcomes on Chemotherapy-Induced Nausea and Vomiting Management in South Korea: Comparison with Asia-Pacific Data of the Pan Australasian Chemotherapy Induced Emesis Burden of Illness Study
Myung Ah Lee, Eun Kyung Cho, Sung Yong Oh, Joong Bae Ahn, Ji Yun Lee, Burke Thomas, Hun Jung, Jong Gwang Kim
Cancer Res Treat. 2016;48(4):1420-1428.   Published online February 12, 2016
DOI: https://doi.org/10.4143/crt.2015.309
AbstractAbstract PDFPubReaderePub
Purpose
This study reported patient outcomes of chemotherapy-induced nausea and vomiting (CINV) prophylaxis for highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) regimens and evaluated its adherence to acute-phase CINV prophylaxis in the Korean population subset of the Pan Australasian Chemotherapy Induced Emesis burden of illness (PrACTICE) study. Materials and Methods This subgroup analysis evaluated 158 Korean patients receiving HEC or MEC and compared the data (wherever possible) with that of 648 patients from the Asia-Pacific (AP) region. Study endpoints included evaluation of primary CINV prophylaxis and adherence to acutephase CINV prophylaxis in cycle 1 (American Society of Clinical Oncology [ASCO] Quality Oncology Practice Initiative [QOPI]).
Results
In South Korea and the AP, a 5-hydroxytryptamine-3 receptor antagonist (5HT3-RA) prophylaxis for the acute phase was administered to 79/80 patients (98.8%) for HEC and 70/71 patients (98.6%) for MEC regimens (QOPI-1). Triple regimen (corticosteroid–5HT3-RA–neurokinin 1-RA) was initiated in 46/80 patients (57.5%) for prophylaxis of acute CINV in cycle 1 of HEC (QOPI-3). Double regimen (corticosteroid–5HT3-RA, with or within NK1-RA) was initiated in 61/71 patients (83.1%) for control of acute CINV in cycle 1 of MEC a(QOPI-2). Conclusion Active management of CINV is necessary in cycle 1 of HEC in South Korea, despite higher rates than the AP region. Adherence to the international guidelines for CINV prophylaxis requires attention in the acute phase in cycle 1 of the HEC regimen.

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Special Article
Tolerability and Outcomes of First-Line Pemetrexed-Cisplatin Followed by Gefitinib Maintenance Therapy Versus Gefitinib Monotherapy in Korean Patients with Advanced Nonsquamous Non-small Cell Lung Cancer: A Post Hoc Descriptive Subgroup Analysis of a Randomized, Phase 3 Trial
Jin Hyoung Kang, Myung-Ju Ahn, Dong-Wan Kim, Eun Kyung Cho, Joo-Hang Kim, Sang Won Shin, Xin Wang, Jong Seok Kim, Mauro Orlando, Keunchil Park
Cancer Res Treat. 2016;48(2):458-464.   Published online October 14, 2015
DOI: https://doi.org/10.4143/crt.2015.135
AbstractAbstract PDFPubReaderePub
Purpose
We recently reported on a randomized, open-label, phase 3 trial comparing pemetrexed-cisplatin chemotherapy followed by gefitinib maintenance therapy (PC/G) with gefitinib monotherapy in patients with non-small cell lung cancer (NSCLC). Here, we report on a post hoc subgroup analysis of that study assessing the demographics and disposition of the Korean patient subgroup, and comparing the tolerability of PC/G and gefitinib monotherapy and the tumor response with respect to epidermal growth factor receptor (EGFR) status.
Materials and Methods
Patients, who were ≥ 18 years, chemonaïve, Korean, light ex-smokers/never-smokers with advanced NSCLC, were randomly assigned (1:1) to PC/G or gefitinib monotherapy. Treatment-emergent adverse events (TEAEs) were graded, and tumor response was measured as change in lesion sum from baseline at best response. The study was registered with ClinicalTrials. gov, NCT01017874.
Results
Overall, 111 Korean patients were treated (PC/G, 51; gefitinib, 60). Between-arm characteristics were balanced and similar to those of the overall population. Treatment discontinuations due to adverse events were low (PC/G: 1, 2.0%; gefitinib: 7, 11.7%). Overall, 92 patients (82.9%) reported ≥ 1 TEAE (PC/G, 44; gefitinib, 48); few patients (PC/G, 16; gefitinib, 7) reported severe TEAEs; the most frequent was neutropenia (PC/G arm) and elevated alanine aminotransferase (gefitinib arm). The lesion sum was decreased by PC/G treatment in most patients, regardless of EGFRmutation status, while gefitinib monotherapy reduced the lesion sum in EGFR-positive patients but had no effect in EGFR-negative patients.
Conclusion
Our results confirm that both PC/G and gefitinib were well tolerated in Korean patients, regardless of EGFR status; however, patients with EGFR wild-type NSCLC may not benefit from gefitinib monotherapy.

Citations

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  • Gefitinib for advanced non-small cell lung cancer
    Esther HA Sim, Ian A Yang, Richard Wood-Baker, Rayleen V Bowman, Kwun M Fong
    Cochrane Database of Systematic Reviews.2018;[Epub]     CrossRef
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Original Article
Randomized Phase II Study of Pemetrexed Versus Gefitinib in Previously Treated Patients with Advanced Non-small Cell Lung Cancer
Young Saing Kim, Eun Kyung Cho, Hyun Sun Woo, Junshik Hong, Hee Kyung Ahn, Inkeun Park, Sun Jin Sym, Sun Young Kyung, Shin Myung Kang, Jeong-Woong Park, Sung Hwan Jeong, Jinny Park, Jae Hoon Lee, Dong Bok Shin
Cancer Res Treat. 2016;48(1):80-87.   Published online March 2, 2015
DOI: https://doi.org/10.4143/crt.2014.307
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to evaluate the efficacy and safety of pemetrexed versus gefitinib in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. Materials and Methods Patients with advanced (stage IIIB or IV) or recurrent NSCLC were randomly assigned to receive either 500 mg/m² of pemetrexed intravenously every 3 weeks or gefitinib 250 mg/day orally. The primary end point was progression-free survival (PFS) at 6 months.
Results
A total of 95 patients were enrolled (47 for pemetrexed and 48 for gefitinib). Most patients were male (72%) and current/ex-smokers (69%), and 80% had non-squamous cell carcinoma. The epidermal growth factor receptor (EGFR) mutation status was determined in 38 patients (40%); one patient per each arm was positive for EGFRmutation. The 6-month PFS rates were 22% and 15% for pemetrexed and gefitinib, respectively (p=0.35). Both arms showed an identical median PFS of 2.0 months and a median overall survival (OS) of 8.5 months. In EGFR wild-type patients, higher response rate (RR) and longer PFS as well as OS were achieved via pemetrexed compared with gefitinib, although there were no significant differences (RR: 39% vs. 9%, p=0.07; median PFS: 6.6 months vs. 3.1 months, p=0.45; median OS: 29.6 months vs. 12.9 months, p=0.62). Toxicities were mild in both treatment arms. Frequently reported toxicities were anemia and fatigue for pemetrexed, and skin rash and anorexia for gefitinib. Conclusion Both pemetrexed and gefitinib had similar efficacy with good tolerability as second-line treatment in unselected patients with advanced NSCLC. However, pemetrexed is considered more effective than gefitinib for EGFR wild-type patients.

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Case Report
Recurrent and Metastatic Trichilemmal Carcinoma of the Skin Over the Thigh: A Case Report
Hyon Seung Yi, Sun Jin Sym, Jinny Park, Eun Kyung Cho, Seung-Yeon Ha, Dong Bok Shin, Jae Hoon Lee
Cancer Res Treat. 2010;42(3):176-179.   Published online September 30, 2010
DOI: https://doi.org/10.4143/crt.2010.42.3.176
AbstractAbstract PDFPubReaderePub

Trichilemmal carcinoma (TC) is an uncommon cutaneous neoplasm that develops from the external root sheath of the hair follicle. It is considered to be a low-grade carcinoma with low metastatic potential. Local recurrence and metastasis are rare after surgical excision. We report here on a case of metastatic TC in the skin over the thigh, and this tumor was treated with cisplatin and cyclophosphamide combination chemotherapy.

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Original Articles
Oxaliplatin, 5-fluorouracil and Leucovorin (FOLFOX-4) Combination Chemotherapy as a Salvage Treatment in Advanced Gastric Cancer
Young Saing Kim, Junshik Hong, Sun Jin Sym, Se Hoon Park, Jinny Park, Eun Kyung Cho, Jae Hoon Lee, Dong Bok Shin
Cancer Res Treat. 2010;42(1):24-29.   Published online March 31, 2010
DOI: https://doi.org/10.4143/crt.2010.42.1.24
AbstractAbstract PDFPubReaderePub
Purpose

This study was designed to determine the efficacy and safety of FOLFOX-4 chemotherapy as a salvage treatment for patients with advanced gastric cancer (AGC).

Materials and Methods

The AGC patients with an ECOG performance status of 0~1 and progressive disease after prior treatments were registered onto this phase II trial. The patients received oxaliplatin (85 mg/m2 on day 1), leucovorin (200 mg/m2 on days 1 and 2) and 5-fluorouracil (400 mg/m2 as a bolus and 600 mg/m2 as a 22-hour infusion on days 1 and 2) every 2 weeks.

Results

For the 42 treated patients, a total of 228 chemotherapy cycles (median: 5, range: 1~12) were administered. Twenty-nine patients (69%) received FOLFOX-4 chemotherapy as a third-(50%) or fourth-line (19%) treatment. On the intent-to-treat analysis, 9 patients (21%) achieved a partial response, which was maintained for 4.6 months. The median progression-free survival and overall survival were 3.0 months and 6.2 months, respectively. The frequently encountered toxicities were neutropenia and gastrointestinal side effects, including anorexia. Although there was one possible treatment-related death, the toxicity profiles were generally predictable and manageable.

Conclusion

Salvage chemotherapy with FOLFOX-4 is an effective and tolerable regimen for those heavily pretreated AGC patients who have a good performance status.

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A Pilot Study of Cisplatin, Irinotecan, Leucovorin and 5-fluorouracil (PILF) Combination Chemotherapy for Advanced Gastric Cancer
Se Hoon Park, Soo Yeon Jeon, Kwang Il Ko, Eunmi Nam, Soo-Mee Bang, Eun Kyung Cho, Dong Bok Shin, Jae Hoon Lee, Woon Ki Lee, Min Chung
Cancer Res Treat. 2006;38(3):121-125.   Published online June 30, 2006
DOI: https://doi.org/10.4143/crt.2006.38.3.121
AbstractAbstract PDFPubReaderePub
Purpose

Irinotecan, in combination with leucovorin/5-fluorouracil (FU) or with cisplatin, is known to be active for treating advanced gastric cancer (AGC). This pilot study evaluated a novel three-drug combination of irinotecan, leucovorin/FU and cisplatin as a first-line treatment of AGC. The primary endpoint was to assess the feasibility in anticipation of conducting a larger phase II study.

Materials and Methods

Chemotherapy-naive AGC patients received irinotecan 150 mg/m2 on day 1, and leucovorin 200 mg/m2 and a 22-h infusion of FU 1000 mg/m2 on days 1 and 2. Cisplatin 30 mg/m2 was administered on day 2. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity.

Results

Of the 17 eligible patients, two patients had an ECOG performance status of 2 and their median age was 48 years (range: 31 to 69). A total of 117 chemotherapy cycles were delivered (median: 6, range: 1 to 12). The causes of treatment discontinuation were disease progression in 9 patients (53%), refusal (35%) and toxicity (12%). Although grade 3 or 4 neutropenia (41% of patients) was the major toxicity that required dose adjustments, only one episode of febrile neutropenia occurred. Grade 3 or 4 nausea and vomiting, diarrhea and fatigue were observed in 35%, 35% and 29% of patients, respectively. None of the patients died of toxicity during treatment. Of the 16 patients who were evaluable for response, 7 (44%) experienced a partial response.

Conclusion

This novel multi-drug combination was tolerated well in patients with AGC. Based on the encouraging efficacy and tolerability, a randomized phase II study is ongoing in this disease setting.

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  • Randomized phase II study of irinotecan, leucovorin and 5-fluorouracil (ILF) versus cisplatin plus ILF (PILF) combination chemotherapy for advanced gastric cancer
    S.H. Park, E. Nam, J. Park, E.K. Cho, D.B. Shin, J.H. Lee, W.K. Lee, M. Chung, S.I. Lee
    Annals of Oncology.2008; 19(4): 729.     CrossRef
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Optimal Timing for the Administration of Capecitabine with Preoperative Chemoradiation for Locally Advanced Rectal Cancer
Young Ju Noh, Won Sik Choi, Jong Hoon Kim, Jin Cheon Kim, Chang Sik Yu, Hee Cheol Kim, Tae Won Kim, Heung Moon Chang, Min Hee Ryu, Seung Do Ahn, Sang-wook Lee, Seong Soo Shin, Jung Eun Lee, Eun Kyung Choi
Cancer Res Treat. 2006;38(1):30-34.   Published online February 28, 2006
DOI: https://doi.org/10.4143/crt.2006.38.1.30
AbstractAbstract PDFPubReaderePub
Purpose

Capecitabine is an oral fluoropyrimidine carbamate and it is known as an effective radiosensitizer. Capecitabine and its metabolite reach their peak concentration in the plasma at 1~2 hours after a single oral administration of capecitabine and the levels fall rapidly thereafter. To verify the radiosensitizing effect of capecitabine that is based on such pharmacokinetic characteristics, we performed a retrospective analysis on the optimal timing of capecitabine administration with performing preoperative chemoradiation for locally advanced rectal cancer.

Materials and Methods

Among 171 patients who were treated with preoperative radiotherapy and concurrent capecitabine administration for rectal cancer, 56 patients were administered capecitabine at 1~2 hours before radiotherapy (group A), and at other time in the other 115 patients (group B). Total mesorectal excision was done at 4 to 6 weeks after the completion of chemoradiation. The radiosensitizing effect of capecitabine was evaluated on the basis of the pathological response.

Results

Complete pathological regression of the primary tumor was observed in 12 patients (21.4%) for group A and in 11 patients (9.6%) for group B (p=0.031). Residual disease less than 0.5 cm (a good response) was observed in 19 patients (33.9%) for group A and in 23 patients (20.0%) for group B (p=0.038). On multivariate analysis, the capecitabine ingestion time showed marginal significance.

Conclusion

When performing preoperative chemoradiation for locally advanced rectal cancer, the radiosensitizing effect of capecitabine was enhanced when it was administered 1 hour before radiotherapy.

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  • Systematic review of treatment intensification using novel agents for chemoradiotherapy in rectal cancer
    R Clifford, N Govindarajah, J L Parsons, S Gollins, N P West, D Vimalachandran
    British Journal of Surgery.2018; 105(12): 1553.     CrossRef
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Synergistic Effect of Ionizing Radiation and β-lapachone against RKO Human Colon Adenocarcinoma Cells
Eun Jung Kim, In-Mi Ji, Ki-Jung Ahn, Eun Kyung Choi, Heon-Jin Park, Byung Uk Lim, Chang W. Song, Heon Joo Park
Cancer Res Treat. 2005;37(3):183-190.   Published online June 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.3.183
AbstractAbstract PDFPubReaderePub
Purpose

To reveal the interaction between β-Lapachone (β-lap) and ionizing radiation in causing cell death in RKO human colon adenocarcinoma cells, and to elucidate the potential usefulness of combined β-lap treatment and radiotherapy for cancer treatment.

Materials and Methods

The cytotoxicities of various treatments were determined in vitro using clonogenic and apoptotic cell death. The changes in cell cycle distribution were studied using flow cytometry and an in vitro kinase assay. The tumor growth was studied using RKO tumors grown s.c. in the hind leg BALB/c- nuslc nude mice.

Results

β-lap caused clonogenic cell death and rapid apoptosis in RKO cells in vitro, in a dose dependent manner. The repair of sublethal radiation damage was almost completely inhibited when cells were maintained in β-lap during the interval between the two-dose irradiation. Flow cytometry study demonstrated that β-lap induced apoptosis, independent of the cell cycle phase, and completely prohibited the induction of radiation-induced G2 arrest in irradiated cells. The prohibition of radiation-induced G2 arrest is unclear, but may be related to the profound suppression of the p53, p21 and cyclin B1-Cdc2 kinase activities observed in cells treated with β-lap. The combination of β-lap and radiation markedly enhanced the radiation-induced growth suppression of tumors.

Conclusion

β-lap is cytotoxic against RKO cells, both in vitro and in vivo, and also sensitized cells to ionizing radiation by inhibiting sublethal radiation damage repair. β-lap is potentially useful as a potent anti-cancer chemotherapy drug and potent radiosensitizer against caner cells.

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  • Artemisia annua L. Polyphenols Enhance the Anticancer Effect of β-Lapachone in Oxaliplatin-Resistant HCT116 Colorectal Cancer Cells
    Eun Joo Jung, Hye Jung Kim, Sung Chul Shin, Gon Sup Kim, Jin-Myung Jung, Soon Chan Hong, Choong Won Kim, Won Sup Lee
    International Journal of Molecular Sciences.2023; 24(24): 17505.     CrossRef
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    Anjali Mittal, Minal Nenwani, Itisam Sarangi, Abhinav Achreja, Theodore S. Lawrence, Deepak Nagrath
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    Yang Zhou, Hui Yan, Qiang Zhou, Ruiling Feng, Penggao Wang, Fang Yang, Yaodong Zhang, Ziqiao Yuan, Bo Zhai
    Frontiers in Pharmacology.2021;[Epub]     CrossRef
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    Ganji Purnachandra Nagaraju, Batoul Farran, Matthew Farren, Gayathri Chalikonda, Christina Wu, Gregory B. Lesinski, Bassel F. El‐Rayes
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    Muhammad Shaalan Beg, Xiumei Huang, Molly A. Silvers, David E. Gerber, Joyce Bolluyt, Venetia Sarode, Farjana Fattah, Ralph J. Deberardinis, Matthew E. Merritt, Xian‐Jin Xie, Richard Leff, Daniel Laheru, David A. Boothman
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    Julio Zukerman-Schpector, Karinne E. Prado, Luccas L. Name, Rodrigo Cella, Mukesh M. Jotani, Edward R. T. Tiekink
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    E J Park, K-j Min, T-J Lee, Y H Yoo, Y-S Kim, T K Kwon
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    Ki Jung Ahn, Hyung Sik Lee, Se Kyung Bai, Chang Won Song
    Radiation Oncology Journal.2013; 31(2): 57.     CrossRef
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A Preliminary Results of a Randomized Trial Comparing Monthly 5-flourouracil and Cisplatin to Weekly Cisplatin Alone Combined with Concurrent Radiotherapy for Locally Advanced Cervical Cancer
Young Seok Kim, Seong Soo Shin, Eun Kyung Choi, Jong Hoon Kim, Seung Do Ahn, Sang-wook Lee, Heon-Jin Park, Young-Tak Kim, Jung-Eun Mok, Joo-Hyun Nam
Cancer Res Treat. 2005;37(1):37-43.   Published online February 28, 2005
DOI: https://doi.org/10.4143/crt.2005.37.1.37
AbstractAbstract PDFPubReaderePub
Purpose

To determine the superior chemotherapeutic regimen between monthly 5-FU plus cisplatin (FP) and weekly cisplatin alone in concurrent chemoradiotherapy for locally advanced cervical cancer, the compliance of treatment, response, survival and toxicities were analyzed between the two arms.

Materials and Methods

Between March 1998 and December 2001, 61 patients with locally advanced cervical cancer (stage IIB through IVA) and negative para-aortic lymph nodes were randomly assigned to either 'monthly FP' (arm I, n=34) or 'weekly cisplatin' (arm II, n=27) with concurrent radiotherapy. The patients of arm I received FP (5-FU 1,000 mg/m2/day + cisplatin 20 mg/m2/day, for 5 days, for 3 cycles at 4 week intervals) and those of arm II received cisplatin (30 mg/m2/day, for 6 cycles at 1 week intervals) with concurrent radiotherapy. The radiotherapy consisted of 41.4~50.4 Gy external beam irradiation in 23~28 fractions to the whole pelvis, with high dose rate brachytherapy delivering a dose of 30~35 Gy in 6~7 fractions to point A. During the brachytherapy, a parametrial boost was delivered. The median follow-up period for survivors was 44 months.

Results

The compliance of treatment in monthly FP weekly cisplatin arms were 62 and 81%, respectively. The complete response rates at 3 months were 96 and 88% in arms I and II, respectively. The 4-year overall survival and disease free survival rates were 64 and 54% in the arm I and 77 and 66% in the arm II, respectively. The incidence of hematologic toxicity more than grade 2 was 29% in the arm I and 15% in the arm II. Only one patient in arm I experienced grade 3 gastrointestinal toxicity. No severe genitourinary toxicity was observed.

Conclusion

No significant difference was observed in the compliance, responses, survival rates and acute toxicities between the two treatment arms. More patients and further follow up will be required.

Citations

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  • American Brachytherapy Task Group Report: A pooled analysis of clinical outcomes for high-dose-rate brachytherapy for cervical cancer
    Jyoti Mayadev, Akila Viswanathan, Yu Liu, Chin-Shang Li, Kevin Albuquerque, Antonio L. Damato, Sushil Beriwal, Beth Erickson
    Brachytherapy.2017; 16(1): 22.     CrossRef
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    Yan Hu, Zhi-Qiang Cai, Xiao-Yan Su
    Asian Pacific Journal of Cancer Prevention.2012; 13(9): 4301.     CrossRef
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    Myong Cheol Lim, Dae Chul Jung, Joo-Young Kim, Sang-Yoon Park
    International Journal of Gynecological Cancer.2009; 19(6): 1125.     CrossRef
  • Adoptive Transfer of Human Papillomavirus E7-specific CTL Enhances Tumor Chemoresponse Through the Perforin/Granzyme-mediated Pathway
    Jeong-Im Sin, Jung-Min Kim, Sung Hwa Bae, In Hee Lee, Jong Sup Park, Hun Mo Ryoo
    Molecular Therapy.2009; 17(5): 906.     CrossRef
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Prospective Phase II Study of Preoperative Chemoradiation with Capecitabine in Locally Advanced Rectal Cancer
Jin-hong Park, Jong Hoon Kim, Seung Do Ahn, Sang-wook Lee, Seong Soo Shin, Jin Cheon Kim, Chang Sik Yu, Hee Cheol Kim, Yoon-Koo Kang, Tae Won Kim, Heung Moon Chang, Min Hee Ryu, Eun Kyung Choi
Cancer Res Treat. 2004;36(6):354-359.   Published online December 31, 2004
DOI: https://doi.org/10.4143/crt.2004.36.6.354
AbstractAbstract PDFPubReaderePub
Purpose

Capecitabine is an attractive oral chemotherapeutic agent that has a radiosensitizing effect and tumor-selectivity. This study was performed to evaluate the efficacy and toxicity of preoperative chemoradiation therapy, when used with oral capecitabine, for locally advanced rectal cancer.

Materials and Methods

A prospective phase II trial of preoperative chemoradiation for locally advanced adenocarcinomas of the lower two-thirds of the rectum was conducted. A radiation dose of 50 Gy over five weeks and a daily dose of 1650 mg/m2 capecitabine in two potions was administered during the entire course of radiation therapy. Surgery was performed with standardized total mesorectal excision four to six weeks after completion of the chemoradiation.

Results

Between January 2002 and September 2003, 61 patients were enrolled onto this prospective phase II trial. The pretreatment clinical stages were T3 in 64% (n=39), T4 in 36% (n=22) and N1-2 in 82% (n=50) of these patients. Fifty-six (92%) patients completed the chemoradiation as initially planned and a complete resection performed in 58 (95%). Down-staging was observed in 45 patients (74%) and a pathologic complete response in 6 (10%). Among the 37 patients with tumors located within 5 cm from the anal verge on colonoscopy, 27 (73%) underwent a sphincter-preserving procedure. No grade 3 and 4 proctitis or hematological toxicities were observed.

Conclusion

Preoperative chemoradiation therapy with capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation, with a low toxicity profile. This combined modality can be regarded as a safe and effective treatment for locally advanced rectal cancer.

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    David D.B. Bates, Maria El Homsi, Kevin J. Chang, Neeraj Lalwani, Natally Horvat, Shannon P. Sheedy
    Clinical Colorectal Cancer.2022; 21(1): 10.     CrossRef
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    Kartik S. Jhaveri, Hooman Hosseini-Nik
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    P. Terry Phang, Xiaodong Wang
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    A. Wibe, W. L. Law, V. Fazio, C. P. Delaney
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    Tae Young Jang, Chang Sik Yu, Yong Sik Yoon, Seok-Byung Lim, Seung-Mo Hong, Tae Won Kim, Jong Hoon Kim, Jin Cheon Kim
    Diseases of the Colon & Rectum.2012; 55(10): 1024.     CrossRef
  • Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck
    J G Kim, S K Sohn, D H Kim, J H Baek, S B Jeon, Y S Chae, K B Lee, J S Park, J H Sohn, J C Kim, I K Park
    British Journal of Cancer.2005; 93(10): 1117.     CrossRef
  • Preoperative Concurrent Chemoradiotherapy with Oral Fluoropyrimidine in Locally Advanced Rectal Cancer: How Good Is Good Enough?
    Hyun Cheol Chung
    Cancer Research and Treatment.2004; 36(6): 341.     CrossRef
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A Phase II Study of Weekly Paclitaxel, Cisplatin and Concurrent Radiation Therapy for Locally-Advanced Unresectable Non-Small Cell Lung Cancer: Early Closure due to Lack of Efficacy
Se Hoon Park, Mi Kyung Kim, Sun Young Kyung, Young-Hee Lim, Chang Hyeok An, Jeong Woong Park, Seong Hwan Jeong, Jae Woong Lee, Kyu Chan Lee, Eun Kyung Cho, Soo Mee Bang, Dong Bok Shin, Jae Hoon Lee
Cancer Res Treat. 2004;36(5):293-297.   Published online October 31, 2004
DOI: https://doi.org/10.4143/crt.2004.36.5.293
AbstractAbstract PDFPubReaderePub
Purpose

In this phase II study, the efficacy and safety of weekly paclitaxel concomitant with cisplatin and thoracic radiotherapy (TRT) was evaluated in patients with locally-advanced unresectable non-small cell lung cancer (NSCLC).

Materials and Methods

Patients with stage III NSCLC (without pleural effusion or cervical lymphadenopathy) received TRT (63 Gy in 35 fractions over 7 weeks) with concurrent weekly cisplatin 20 mg/m2 and paclitaxel 40 mg/m2/week infused over 3 hours. In patients without evidence of disease progression, the administration of a further 2 cycles of consolidation chemotherapy, consisting of paclitaxel 175 mg/m2 and cisplatin 75 mg/m2, were planned after completion of the TRT.

Results

Between Feb 2000 and Dec 2002, 20 patients were entered into the study; 13 completed all 7 weeks of treatment (median 7.6 weeks; range 3.3 to 9.4). Seven out of 16 (43.8%) objective responses were observed, with 15 (75%) patients experiencing at least one episode of grade 3/4 toxicity. The main toxicities were moderate to severe neutropenia and gastrointestinal toxicity.

Conclusion

The unsatisfactory response rate and the high incidence of grade 3/4 hematologic and non-hematologic toxicities, including 7 early discontinuations of treatment and exceeding the study stopping rules, prompted the early closure of the study. In view of the activity observed, the protocol was amended to protracted continuous infusion paclitaxel, cisplatin and concurrent TRT.

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Influence of Estrogen and Polyamines on Mifepristone-induced Apoptosis in Prostate Cancer Cells
Eun Kyung Choi, Hwi-June Song, Min S. Park, Byeong Gee Kim
Cancer Res Treat. 2004;36(1):85-90.   Published online February 29, 2004
DOI: https://doi.org/10.4143/crt.2004.36.1.85
AbstractAbstract PDFPubReaderePub
Purpose

Although androgens are the main steroids controlling the growth of prostate glands, estrogens are also important in the regulation of its growth. Prostate cancer cells, like other cancer cells, maintain high levels of polyamines. In LNCaP cells, apoptosis is induced by mifepristone. During the process of cell death, the regulation of ROS production, caspase-3 activation and poly (ADP-ribose) polymerase cleavage were investigated in the presence of estrogen and polyamines to identify their possible roles.

Materials and Methods

The cell growth was assessed using the MTT assay, and theintracellular ROS production by the DCFH-DA assay. The p53 protein expression, activation of caspase-3 and PARP cleavage were checked by Western blotting, with specific antibodies to each.

Results

The growth and viability of the cells were significantly inhibited, in a dose- and time-dependent manners, by mifepristone (MIF) treatment. The production of ROSwere dependent on the MIF dosage. The activation of caspase-3 and cleavage of PARPalso increased with the duration of MIF treatment. The expression of p53 protein also increased with increases in the MIF incubation time. E2 severely inhibited the ROS production, caspase-3 activation and PARP cleavage. However, polyamines only inhibited the ROS production, without influencing the caspase-3 activation or PARP cleavage.

Conclusion

In LNCaP cells, MIF induces apoptosis through ROS production. The expression of p53 protein, caspase-3 activation and PARP cleavage accompanied the process of apoptosis. The apoptotic processes were inhibited by E2, but polyamines only inhibited the ROS production, implying the multifunctional role of E2, in addition to its role as a free radical scavenger.

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  • Dexamethasone along with ciprofloxacin modulates S. aureus induced microglial inflammation via glucocorticoid (GC)-GC receptor-mediated pathway
    Rajen Dey, Biswadev Bishayi
    Microbial Pathogenesis.2020; 145: 104227.     CrossRef
  • Synergistic Effect of Ionizing Radiation and β-lapachone against RKO Human Colon Adenocarcinoma Cells
    Eun Jung Kim, In-Mi Ji, Ki-Jung Ahn, Eun Kyung Choi, Heon-Jin Park, Byung Uk Lim, Chang W. Song, Heon Joo Park
    Cancer Research and Treatment.2005; 37(3): 183.     CrossRef
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Radioresponse of Hepatocellular Carcinoma-Treatment of Lymph Node Metastasis
Sang Min Yoon, Jong Hoon Kim, Eun Kyung Choi, Seung Do Ahn, Sang-wook Lee, Byong Yong Yi, Young Wha Chung, Young Sang Lee, Dong Jin Seo
Cancer Res Treat. 2004;36(1):79-84.   Published online February 29, 2004
DOI: https://doi.org/10.4143/crt.2004.36.1.79
AbstractAbstract PDFPubReaderePub
Purpose

To analyze the radioresponse of hepatocellular carcinomas (HCC), using accurate measurements of the tumor size in extrahepatic lymph node metastasis, and to obtain information for the future treatment of primary intrahepatic lesions.

Materials and Methods

Fifty-one extrahepatic lymph node metastases from primary HCCs, which could be treated by external radiotherapy alone, were included in this study. The radiation dose ranged from 30 to 51 Gy with fraction sizes of 2.0~3.0 Gy. Responses were determined by measuring the areas on CT scans 0, 1 and 3 months after the completion of radiotherapy. The median follow-up period of the surviving patients was 10 months.

Results

The overall response rate was 76%, and the important factors were; total dose of radiation, time dose fractionation (TDF) value and the biologically effective dose (BED). A dose of 45 Gy or higher showed an objective response rate of 93%, and if the TDF value was higher than 90, a similar result was observed. In about half (47%) of the patients the maximum response was observed at 3 months or later. The response duration was observable in 14 patients surviving 12 months or longer. Regrowth of irradiated lesions were observed in 4 (66.7%) patients among those who received less than 45 Gy, and in 4 (50%) among those who were treated with 45 Gy or more. There was a statistically significant difference in the survivals between the responders and non-responders (p=0.008). Gastrointestinal bleeding or ulceration was observed in 8 patients, including 3 with NCI common toxicity criteria grade III or higher.

Conclusion

Radiotherapy was an effective palliative modality for extrahepatic metastasis in HCCs. A radiation dose of 45 Gy or higher (or a TDF value ≥90), was required for a major response.

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    Doo Yeul Lee, Joong-Won Park, Tae Hyun Kim, Ju Hee Lee, Bo Hyun Kim, Sang Myung Woo, Sang Soo Kim, Woo Jin Lee, Dae Yong Kim, Chang-Min Kim
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A Phase II Study of Paclitaxel and Cisplatin Combination Chemotherapy in Advanced Non-small-cell Lung Cancer
Jung Ae Lee, Keun Seok Lee, Jin Seok Ahn, Jae Ho Byun, Hun Ho Song, Dae Young Zang, Young Iee Park, Young Suk Park, Eun Kyung Mo, Dong Kyu Kim, Myung Goo Lee, In Gyu Hyun, Ki Suck Jung, Soo Mee Bang, Gye Young Park, Jeong Woong Park, Eun Kyung Cho, Seong Hwan Jeong, Dong Bok Shin, Jae Hoon Lee
Cancer Res Treat. 2003;35(3):239-244.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.239
AbstractAbstract PDF
PURPOSE
Paclitaxel and cisplatin, active drugs in the treatment of non-small-cell lung cancer (NSCLC), have been found to be synergistic and less myelotoxic in combination when the paclitaxel is given 24 hr prior to the cisplatin. Their antitumor activity and toxicity in patients with advanced NSCLC has been evaluated herein. MATERIALS AND METHODS: Seventy-four chemonaive patients, with advanced NSCLC, were enrolled. Paclitaxel, 175 mg/m2, was administered on day 1, followed 24 hr later by cisplatin, 75 mg/m2, on day 2. RESULTS: The overall response rate, median time to progression and median survival time were 51%, 7.1 months (95% confidence interval (CI), 5.5~8.7 months) and 13.7 months (95% CI, 11.3~16.1 months), respectively. There were significant differences in the overall survival rates in relation to stage and the ECOG performance status(PS). The toxicity was mainly nonhematological. Grade > or =3 neuropathy occurred in 2 (3%) patients, myalgia in 3 (4%), and bone pain in 3 (4%). The hematological toxicity was mild, and no grade 3 or 4 neutropenia was observed.
CONCLUSION
The combination of paclitaxel and cisplatin is an effective and tolerable treatment regimen for advanced NSCLC during first line chemotherapy. The main toxicity was nonhematological, such as peripheral neuropathy, myalgia and bone pain, whereas the hematological toxicity itself was mild.

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  • The Efficacy and Safety of Padexol® (Paclitaxel) and Cisplatin for Treating Advanced Non-small Cell Lung Cancer
    Hoon-Kyo Kim, Jun Suk Kim, Hun Mo Ryoo, Dong Gun Shin, Byoung Young Shim, Kyong Hwa Park, Sung Hwa Bae, Chi Hong Kim
    Cancer Research and Treatment.2006; 38(2): 66.     CrossRef
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Patterns of Failure and Prognostic Factors in Anal Cancer Treated with Radiotherapy
Kyoung Ju Kim, Jong Hoon Kim, Eun Kyung Choi, Seung Do Ahn, Sang Wook Lee, Jin Cheon Kim, Chang Sik Yu, Hee Cheol Kim, Je Hwan Lee, Tae Won Kim
Cancer Res Treat. 2003;35(2):141-147.   Published online April 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.2.141
AbstractAbstract PDF
PURPOSE
To analyze the patterns of failure and prognostic factors affecting the local control and survivals in anal cancer treated with definitive radiotherapy, and to find the most effective treatment modality. MATERIALS AND METHODS: Thirty consecutive patients, with primary cancers of the anal canal, were treated using radiotherapy, both with and without 5-FU based concurrent chemotherapy. According to the AJCC tumor stage, six patients hadwere stage I, 11 had stage II, 2 had stage IIIA, and 11 had stage IIIB tumors. The median radiation dose was 45 Gy (30-72 Gy), and with 23 patients receivinged concurrent chemotherapy (5-FU and mitomycin C in 12 patients, 5-FU and cisplatin in 7, and other drugs in 4). The Mmedian follow up period was 43 months, (ranginge, from 8- to 99 months). RESULTS: Among the 1630 patients who16 were treated without surgical resection beforeprior to the radiotherapy, and a complete remission was observed in 12 patients (75%), a partial remission in 3 (19%), and a local progression in the other one patient. The Llocal failures, including persistent disease, were observed in 10 (33%), and the patients with higher T-stages (T3-4) had higher rates of local failure rates (T1-2, 21% vs. T3-4, 72%, p=0.03). Distant metastases were found in 4 patients (13%). The five year survival and disease free survival rates were 64% and 53%, respectively. The factors which affectinged the 5 year local relapse free survival were T-stage (74.9% in T1-2 vs. 28.6% in T3-4, p=0.01), and the existence of a gross tumor beforeprior to radiotherapy (84.6%, no residual vs. 45.1% with residual, p=0.03).
CONCLUSION
A Llocal recurrence was the major failure pattern in anal cancers, and the factors affecting a local failure were the T-stage and tumor volume beforeprior to radiotherapy. A Rradiation dose around 45 Gy was sufficient to control tumors of the earlier T stage tumors, but a higher dose should be considered for with more advanced lesions.
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Ependymoma: a Retrospective Analysis of 25 Cases
Young Seok Kim, Seung Do Ahn, Eun Kyung Choi, Jong Hoon Kim, Sang Wook Lee, Young Ju Noh, Chang Jin Kim, Jeong Hoon Kim, Byung Duk Kwun
Cancer Res Treat. 2002;34(6):450-456.   Published online December 31, 2002
DOI: https://doi.org/10.4143/crt.2002.34.6.450
AbstractAbstract PDF
PURPOSE
We evaluated the patterns of failure, survival rate, prognostic factors and treatment related complication in postoperative radiation treatment of patients with ependymoma.
MATERIALS AND METHODS
We retrospectively analyzed 25 patients with histologically confirmed ependymoma treated between Jun. 1990 and Jun. 2001 with postoperative radiotherapy at Asan Medical Center. The study group comprised of 16 men and 9 women, with a median age of 23 years; including 6 supratentorial, 15 infratentorial and 4 spinal cord lesions. The extents of resection were ranked as either: gross total, near total, subtotal, partial resection or biopsy, with these types of surgical resection being performed in 13, 3, 6, 1 and 2 patients, respectively. Twelve of the patients had low grade ependymoma, and the other 13 a high grade tumor. The postoperative irradiation was administered using 4 MV or 6 MV photons, up to median dose of 55.0 Gy (range, 45.0~59.4 Gy), with the radiation field encompassing the preoperative tumor volume plus a 2 cm margin. Only 8 of the patients received either pre- or postoperative chemotherapy. The median follow-up period of survivors was 43 months.
RESULTS
Ten of the 25 patients (40%) developed a recurrence, and 5 died. Of the 10 recurred patients, 6 showed an in-field recurrence, and one developed both an in-field and an out of field recurrence. The remaining 3 patients showed an out of field recurrence, including one case with a leptomeningeal recurrence. The 5-year overall survival, and progression-free, survival rates were 74.0 and 56.1%, respectively. The histological grades were statistically significant prognostic factors of the overall and progression-free survival rates. There were no significant treatment related complications, with the exception of one case of panhypopituitarism, which occurred 30 months after completion of the radiotherapy.
CONCLUSION
The main pattern of recurrence was due to local failure. In order to improve the local control, and to reduce complications, advanced radiation treatment techniques, such as 3 dimensional radiotherapy, may be needed.

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  • Clinical outcomes of radiotherapy for spinal cord ependymoma with adverse prognostic features: a single-center study
    Hwa Kyung Byun, Seong Yi, Hong In Yoon, Se Hoon Kim, Jaeho Cho, Chang-Ok Suh
    Journal of Neuro-Oncology.2018; 140(3): 649.     CrossRef
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Concurrent Etoposide/Cisplatin Combination Chemotherapy (EP) and Thoracic Radiotherapy after Two Cycles of EP for Limited Stage Small Cell Lung Cancer
Hee Jung Sohn, Sang We Kim, Jin Hee Ahn, Hye Jin Kang, Sarah Park, Heon Nyoung Jung, Cheol Won Suh, Woo Kun Kim, Sang Wook Lee, Eun Kyung Choi, Sang Do Lee, Woo Sung Kim, Dong Sun Kim, Won Dong Kim, Jung Shin Lee
Cancer Res Treat. 2002;34(6):409-415.   Published online December 31, 2002
DOI: https://doi.org/10.4143/crt.2002.34.6.409
AbstractAbstract PDF
Purpose
s: Although the standard management of limited stage small cell lung cancer is concurrent platinum-based chemotherapy with thoracic radiotherapy (TRT), the optimal timing of the TRT remains controversial. We investigated the feasibility of concurrent chemoradiation for the patients with limited stage small cell lung cancer after 2 cycles of combination chemotherapy with Etoposide/Cisplatin (EP).
MATERIALS AND METHODS
EP consisted of Etoposide 100 mg/m2 on day 1 to 3 and Cisplatin 70 mg/m2 on day 1. Six cycles were given to the responders every 4 weeks. Total 55 Gy (1.8 Gy once-daily or 1.2 Gy twice-daily, 5 days per week) of TRT were given to the patients who showed at least a partial response after 2 cycles of EP. The other patients were treated by the physician's decision. The patients with complete remission were recommended to receive prophylactic cranial irradiation.
RESULTS
Fifty patients were enrolled. Thirty-five (70%) of them showed responses (2 complete remissions and 33 partial remissions) after 2 cycles of EP. Thirty-three of the responders were given TRT starting with the 3rd cycle of EP. The nonresponders were treated with salvage chemotherapy and TRT. After completion of treatment for 50 patients, the overall response rate was 86% (29 complete remissions, 14 partial remissions). One patient (2%) showed stable disease, and 6 (12%) showed a progressive disease. The median progression free survival was 326 days and the median survival time was 410 days. One-, 2-, 3-, 4- and 5-year survival rates were 62%, 24%, 14%, 9% and 6%, respectively. As hematologic toxicities during chemoradiation, 35.1% with grade III/IV neutropenia and 18.9% with grade III/IV thrombocytopenia were noted. Grade II/III radiation pneumonitis and radiation esophagitis were noted in 5/1 and 13/1 patients (15.2%/ 3.0% and 39.4%/3.0%), respectively. One patient died of septicemia during chemoradiation.
CONCLUSION
The concurrent EP and TRT after 2 cycles of EP was feasible in limited stage small cell lung cancer. Further study is required for the indentification of optimum timing of TRT during combination chemotherapy.

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  • Effect of early chemoradiotherapy in patients with limited stage small cell lung cancer
    In-Bong Ha, Bae-Kwon Jeong, Hojin Jeong, Hoon-Sik Choi, Gyu-Young Chai, Myoung-Hee Kang, Hoon Gu Kim, Gyeong-Won Lee, Jae-Beom Na, Ki-Mun Kang
    Radiation Oncology Journal.2013; 31(4): 185.     CrossRef
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Preliminary Results of Paclitaxel, Cisplatin and Concurrent High-Dose Radiation Therapy for Locally Advanced Non-Small-Cell Lung Cancer
Sang wook Lee, Eun Kyung Choi, Suk Joong Oh, Cheol Won Suh, Sang We Kim, Jung Shin Lee, Dong Soon Kim, Won Dong Kim, Woo Seong Kim, Sang Do Lee, Jong Hoon Kim, Seung Do Ahn, Kyoung Ju Kim, Young Ju Noh
Cancer Res Treat. 2002;34(5):345-351.   Published online October 31, 2002
DOI: https://doi.org/10.4143/crt.2002.34.5.345
AbstractAbstract PDF
PURPOSE
To investigate the feasibility, toxicity and response rate, of concurrent chemoradiation therapy with paclitaxel/cisplatin in stage III locally advanced non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
Between May 1999 and December 2000, 80 patients with stage III NSCLC were enrolled in a prospective protocol. Radiotherapy was given to a total dose of 70.2 Gy (daily fraction of 1.8 Gy for 5 days), over an 8 week period, on the gross tumor volume, combined with chemotherapy. The concurrent chemotherapy consisted of paclitaxel (40 mg/m2) and 20 mg/m2 cisplatin per week for 8 consecutive weeks. All patients received 3-D conformal radiotherapy using CT-simulated planning. Acute toxicities were evaluated by the RTOG scale. The median follow-up period was 16 months, ranging from 3 to 29 months.
RESULTS
Of the 80 patients, 71 received treatment per protocol, with minor variation of protocol delivery. The median age of the patients was 60 years. Karnofsky Performance status were 100 and 90 in 62 patients, and 80 and 70 in 9, respectively. Weight loss of less than 5% for 6 months was observed in 22 patients. The response to treatment was evaluated from the radiological findings. Complete and partial responses were observed in 8 and 51 patients, respectively. Ultimately, 82% of patients (included complete responses: 8 cases) obtained more than a partial response. Although, radiation induced esophagitis was the most common treatment related toxicity, occurring in 44 patients (69%), severe radiation esophagitis like, grade 3, was observed in only 3 patients, and the most acute toxicities had completely recovered 1 month following treatment. The overall 2-year actuarial and progression free survivals were 56 and 45%, respectively.
CONCLUSION
This combined modality has activity with manageable toxicity and 23 months in mean survival time in patients with stage III NSCLC. A longer follow up will be required to realise the expected higher survival of these results.

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  • A Phase II Study of Weekly Paclitaxel, Cisplatin and Concurrent Radiation Therapy for Locally-Advanced Unresectable Non-Small Cell Lung Cancer: Early Closure due to Lack of Efficacy
    Se Hoon Park, Mi Kyung Kim, Sun Young Kyung, Young-Hee Lim, Chang Hyeok An, Jeong Woong Park, Seong Hwan Jeong, Jae Woong Lee, Kyu Chan Lee, Eun Kyung Cho, Soo Mee Bang, Dong Bok Shin, Jae Hoon Lee
    Cancer Research and Treatment.2004; 36(5): 293.     CrossRef
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