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General
Impact of Patient Sex on Adverse Events and Unscheduled Utilization of Medical Services in Cancer Patients Undergoing Adjuvant Chemotherapy: A Multicenter Retrospective Cohort Study
Songji Choi, Seyoung Seo, Ju Hyun Lee, Koung Jin Suh, Ji-Won Kim, Jin Won Kim, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jwa Hoon Kim, Tae Won Kim, Yong Sang Hong, Sun Young Kim, Jeong Eun Kim, Sang-We Kim, Dae Ho Lee, Jae Cheol Lee, Chang-Min Choi, Shinkyo Yoon, Su-Jin Koh, Young Joo Min, Yongchel Ahn, Hwa Jung Kim, Jin Ho Baek, Sook Ryun Park, Jee Hyun Kim
Cancer Res Treat. 2024;56(2):404-413.   Published online November 7, 2023
DOI: https://doi.org/10.4143/crt.2023.784
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The female sex is reported to have a higher risk of adverse events (AEs) from cytotoxic chemotherapy. Few studies examined the sex differences in AEs and their impact on the use of medical services during adjuvant chemotherapy. This sub-study aimed to compare the incidence of any grade and grade ≥ 3 AEs, healthcare utilization, chemotherapy completion rate, and dose intensity according to sex.
Materials and Methods
This is a sub-study of a multicenter cohort conducted in Korea that evaluated the impact of healthcare reimbursement on AE evaluation in patients who received adjuvant chemotherapy between September 2013 and December 2016 at four hospitals in Korea.
Results
A total of 1,170 patients with colorectal, gastric, or non–small cell lung cancer were included in the study. Female patients were younger, had fewer comorbidities, and experienced less postoperative weight loss of > 10%. Females had significantly higher rates of any grade AEs including nausea, abdominal pain, stomatitis, vomiting, and neutropenia, and experienced more grade ≥ 3 neutropenia, nausea, and vomiting. The dose intensity of chemotherapy was significantly lower in females, and they also experienced more frequent dose reduction after the first cycle. Moreover, female patients receiving platinum-containing regimens had significantly higher rates of unscheduled outpatient visits.
Conclusion
Our study found that females experienced a higher incidence of multiple any-grade AEs and severe neutropenia, nausea, and vomiting, across various cancer types, leading to more frequent dose reductions. Physicians should be aware of sex differences in AEs for chemotherapy decisions.

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  • Toxicidad del esquema FOLFOX-6, asociado o no a bolo de 5-fluorouracilo, en cáncer colorrectal metastásico
    María Teresa Garrido Martínez, María Rodríguez Jorge, Ignacio García Giménez, María Isabel Guzmán Ramos, Salvador Grutzmancher Sáiz, Victoria Aviñó Tarazona
    Farmacia Hospitalaria.2024;[Epub]     CrossRef
  • 3,256 View
  • 157 Download
  • 1 Crossref
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Gastrointestinal cancer
Role of Esophagectomy after Chemoradiation Therapy in Patients with Locally Advanced Squamous Cell Carcinoma: A Comparative Analysis Stratified by Clinical Response to Chemoradiation Therapy
Jesang Yu, Jong Hoon Kim, Sung-Bae Kim, Sook Ryun Park, Young-Hee Kim, Hyeong Ryul Kim, Hyun Joo Lee, Ho June Song, Kye Jin Song, Jeong Yun Jang, Yoon Young Jo, Ye Jin Yoo
Cancer Res Treat. 2022;54(4):1148-1156.   Published online December 20, 2021
DOI: https://doi.org/10.4143/crt.2021.885
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the long-term effect of esophagectomy in patients with esophageal squamous cell carcinoma (ESCC) by comparing the chemoradiotherapy (CRT)-only group and the trimodality treatment (TMT) group who received concurrent CRT followed by surgery.
Materials and Methods
We included 412 operable ESCC patients treated with TMT or CRT between January 2005 and December 2015. The oncological outcomes of the two groups were compared using a weighted Cox proportional-hazards model with inverse probability of treatment weighting (IPTW).
Results
The median survival time was 64 and 32 months in the TMT (n=270) and CRT (n=142) groups, respectively (p < 0.001). After IPTW, the median overall survival (OS) remained significantly higher in the TMT group than in the CRT group (61 months vs. 32 months, p=0.016). Moreover, the TMT group showed a better local recurrence-free rate (LRFR, p < 0.001) and distant metastasis-free rate (p=0.007). In the subgroup of patients with clinical complete response (cCR), the OS was not significantly different between the two groups, both before and after IPTW adjustment (p=0.35 and p=0.93). However, among non-cCR patients, the OS was significantly higher in the TMT group (64% vs. 45%, p < 0.001).
Conclusion
In patients with locally advanced ESCC, TMT was superior to CRT in terms of OS and LRFR. Such difference was more prominent in the non-cCR subgroup. In patients who achieved cCR, esophagectomy was effective in improving LRFR but not OS, suggesting that esophagectomy may be omitted in complete responders.

Citations

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  • Comparison of esophageal cancer survival after neoadjuvant chemoradiotherapy plus surgery versus definitive chemoradiotherapy: A systematic review and meta-analysis
    Junli Ke, Yujie Xie, Shenyang Huang, Wei Wang, Zhengang Zhao, Wanli Lin
    Asian Journal of Surgery.2024; 47(9): 3827.     CrossRef
  • Multi-disciplinary management of esophageal carcinoma: Current practices and future directions
    Chanyoot Bandidwattanawong
    Critical Reviews in Oncology/Hematology.2024; 197: 104315.     CrossRef
  • Practice pattern and risk of not receiving planned surgery after neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma
    Tae Hee Hong, Tae Ho Kim, Genehee Lee, Jeonghee Yun, Yeong Jeong Jeon, Junghee Lee, Sumin Shin, Seong Yong Park, Jong Ho Cho, Yong Soo Choi, Young Mog Shim, Jong-Mu Sun, Dongryul Oh, Hong Kwan Kim
    European Journal of Cardio-Thoracic Surgery.2024;[Epub]     CrossRef
  • Induction Therapy of Tislelizumab Combined with Cisplatin and 5-Fluorouracil and Subsequent Conversion Surgery in Patients with Unresectable Advanced Esophageal Squamous Cell Carcinoma: A Phase 2, Single Center Study
    Tongpeng Xu, Jianan Bai, Kun Zhao, Xiaofeng Chen, Shuhui Wang, Shusheng Zhu, Chongqi Sun, Chenhui Zhao, Ting Wang, Ling Zhu, Meizhen Hu, Fei Pang, Junling Zhang, Wei Wang, Yongqian Shu, Fang Li, Yue Zhou
    Annals of Surgical Oncology.2024; 31(13): 9321.     CrossRef
  • Unveiling Therapeutic Targets for Esophageal Cancer: A Comprehensive Review
    Rakesh Acharya, Ananya Mahapatra, Henu Kumar Verma, L. V. K. S. Bhaskar
    Current Oncology.2023; 30(11): 9542.     CrossRef
  • Nomogram for predicting pathologic complete response following preoperative chemoradiotherapy in patients with esophageal squamous cell carcinoma
    Young Seob Shin, Jeong Yun Jang, Ye Jin Yoo, Jesang Yu, Kye Jin Song, Yoon Young Jo, Sung-Bae Kim, Sook Ryun Park, Ho June Song, Yong-Hee Kim, Hyeong Ryul Kim, Jong Hoon Kim
    Gastroenterology Report.2023;[Epub]     CrossRef
  • 5,673 View
  • 124 Download
  • 8 Web of Science
  • 6 Crossref
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Lung and Thoracic cancer
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

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  • 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
  • 8,653 View
  • 272 Download
  • 2 Web of Science
  • 3 Crossref
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Gastrointestinal cancer
Real-World Efficacy Data and Predictive Clinical Parameters for Treatment Outcomes in Advanced Esophageal Squamous Cell Carcinoma Treated with Immune Checkpoint Inhibitors
Jwa Hoon Kim, Bokyung Ahn, Seung-Mo Hong, Hwoon-Yong Jung, Do Hoon Kim, Kee Don Choi, Ji Yong Ahn, Jeong Hoon Lee, Hee Kyoung Na, Jong Hoon Kim, Yong-Hee Kim, Hyeong Ryul Kim, Hyun Joo Lee, Sung-Bae Kim, Sook Ryun Park
Cancer Res Treat. 2022;54(2):505-516.   Published online June 23, 2021
DOI: https://doi.org/10.4143/crt.2020.1198
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the real-world efficacy of immune checkpoint inhibitors (ICIs), and to identify clinicolaboratory factors to predict treatment outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving ICIs.
Materials and Methods
Sixty patients with metastatic or unresectable ESCC treated with nivolumab (n=48) or pembrolizumab (n=12) as ≥ second-line treatment between 2016 and 2019 at Asan Medical Center were included.
Results
The median age of the patients was 68 years (range, 52 to 76 years), and 93.3% were male. Most patients had metastatic disease (81.7%) and had been previously treated with fluoropyrimidines, platinum, and taxane. In 53 patients with measurable disease, the overall response rate and disease control rate were 15.1% and 35.8%, respectively. With a median follow-up duration of 16.0 months, the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval [CI], 1.54 to 2.19) and 6.4 months (95% CI, 4.77 to 8.11), respectively. After multivariate analysis, recent use of antibiotics, low prognostic nutrition index (< 35.93), high Glasgow Prognosis Score (≥ 1) at baseline, and ≥ 1.4-fold increase in neutrophil-to-lymphocyte ratio after one cycle from baseline were significantly unfavorable factors for both PFS and OS. Younger age (< 65 years) was a significant factor for unfavorable PFS and hyponatremia (< 135 mmol/L) for unfavorable OS.
Conclusion
The use of ICIs after the failure of chemotherapy showed comparable efficacy in patients with advanced ESCC in real practice; this may be associated with host immune-nutritional status, which could be predicted by clinical and routine laboratory factors.

Citations

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  • Clinical features and treatment outcomes of PD-1 inhibitor therapy in elderly patients (≥ 65 years) with advanced esophageal squamous cell carcinoma: a real-world study
    Yi Yu, Tao Wu, Wei Gan, Can Liu, Ran Zhang, Jinxiu Zheng, Jianping Xiong, Jun Chen, Junhe Li
    Clinical and Translational Oncology.2024; 26(9): 2360.     CrossRef
  • Pembrolizumab for recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus: a drug safety evaluation
    Kazumasa Yamamoto, Shun Yamamoto, Ken Kato
    Expert Opinion on Drug Safety.2024; 23(6): 667.     CrossRef
  • Efficacy and survival of nivolumab treatment for recurrent/unresectable esophageal squamous-cell carcinoma: real-world clinical data from a large multi-institutional cohort
    Tomoki Makino, Shigeto Nakai, Kota Momose, Kotaro Yamashita, Koji Tanaka, Hiroshi Miyata, Sachiko Yamamoto, Masaaki Motoori, Yutaka Kimura, Yuki Ushimaru, Motohiro Hirao, Jin Matsuyama, Yusuke Akamaru, Yukinori Kurokawa, Hidetoshi Eguchi, Yuichiro Doki
    Esophagus.2024; 21(3): 319.     CrossRef
  • The impact of antibiotic use in gastrointestinal tumors treated with immune checkpoint inhibitors: systematic review and meta-analysis
    Faizah M. Alotaibi, Ibrahim Abdullah S. Albalawi, Amna M. Anis, Hawazin Alotaibi, Seham Khashwayn, Kanan Alshammari, Jaffar A. Al-Tawfiq
    Frontiers in Medicine.2024;[Epub]     CrossRef
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    Sho Sato, Takashi Suzuki, Takashi Chinen, Hironori Yamaguchi, Yusuke Suzuki, Nobukazu Hokamura, Zenichiro Saze, Koji Kono, Keita Takahashi, Fumiaki Yano, Tsutomu Sato, Takashi Kosaka, Itaru Endo, Yasushi Ichikawa, Yutaka Miyawaki, Hiroshi Sato, Hideaki Sh
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    Xu Tong, Meiyuan Jin, Lulu Wang, Dongli Zhang, Yuping Yin, Qian Shen
    Frontiers in Immunology.2024;[Epub]     CrossRef
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    Lilong Zhang, Wangbin Ma, Zhendong Qiu, Tianrui Kuang, Kunpeng Wang, Baohong Hu, Weixing Wang
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Impact of Patient Characteristics on the Outcomes of Patients with Gastrointestinal Cancers Treated with Immune Checkpoint Inhibitors
    Hyejee Ohm, Omar Abdel-Rahman
    Current Oncology.2023; 30(1): 786.     CrossRef
  • A systematic review and meta-analysis evaluating the impact of antibiotic use on the clinical outcomes of cancer patients treated with immune checkpoint inhibitors
    Athéna Crespin, Clément Le Bescop, Jean de Gunzburg, Fabien Vitry, Gérard Zalcman, Julie Cervesi, Pierre-Alain Bandinelli
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • The Use of Antibiotics During Immune Checkpoint Inhibitor Treatment Is Associated with Lower Survival in Advanced Esophagogastric Cancer
    Lilong Zhang, Tianrui Kuang, Dongqi Chai, Wenhong Deng, Peng Wang, Weixing Wang
    International Immunopharmacology.2023; 119: 110200.     CrossRef
  • Predictive Impact of Prognostic Nutritional Index in Patients with Cancer Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
    Xin-Tian Xu, Yu Qian, Meng-Xing Tian, Chen-Chen Ding, Huan Guo, Jing Tang, Guo-Liang Pi, Yuan Wu, Zhu Dai, Xin Jin
    Nutrition and Cancer.2023; 75(6): 1413.     CrossRef
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    Ning Chen, Xiaoling Xu, Yun Fan
    Therapeutic Advances in Medical Oncology.2023;[Epub]     CrossRef
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    豊 木村
    The Japanese Journal of SURGICAL METABOLISM and NUTRITION.2023; 57(6): 183.     CrossRef
  • Prognostic and predictive impact of neutrophil‐to‐lymphocyte ratio and HLA‐I genotyping in advanced esophageal squamous cell carcinoma patients receiving immune checkpoint inhibitor monotherapy
    Lin Wang, Yanrong Zhu, Bo Zhang, Xi Wang, Hongnan Mo, Yuchen Jiao, Jiachen Xu, Jing Huang
    Thoracic Cancer.2022; 13(11): 1631.     CrossRef
  • Prognostic Nutritional Index Predicts Response and Prognosis in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
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    Frontiers in Nutrition.2022;[Epub]     CrossRef
  • The impact of antibiotic use on clinical features and survival outcomes of cancer patients treated with immune checkpoint inhibitors
    Jiaxin Zhou, Guowei Huang, Wan-Ching Wong, Da-hai Hu, Jie-wen Zhu, Ruiman Li, Hong Zhou
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • The prognostic value of prognostic nutritional index in advanced cancer receiving PD‐1/L1 inhibitors: A meta‐analysis
    Pengfei Li, Yutian Lai, Long Tian, Qinghua Zhou
    Cancer Medicine.2022; 11(16): 3048.     CrossRef
  • Intratumoral immunotherapy using a TLR2/3 agonist, L-pampo, induces robust antitumor immune responses and enhances immune checkpoint blockade
    Won Suk Lee, Dong Sung Kim, Jeong Hun Kim, Yoonki Heo, Hannah Yang, Eun-Jin Go, Jin Hyoung Kim, Seung Joon Lee, Byung Cheol Ahn, Jung Sun Yum, Hong Jae Chon, Chan Kim
    Journal for ImmunoTherapy of Cancer.2022; 10(6): e004799.     CrossRef
  • Focus on the Dynamics of Neutrophil-to-Lymphocyte Ratio in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis and Systematic Review
    Yusheng Guo, Dongqiao Xiang, Jiayu Wan, Lian Yang, Chuansheng Zheng
    Cancers.2022; 14(21): 5297.     CrossRef
  • The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis
    Deniz Can Guven, Taha Koray Sahin, Enes Erul, Alessandro Rizzo, Angela Dalia Ricci, Sercan Aksoy, Suayib Yalcin
    Frontiers in Molecular Biosciences.2022;[Epub]     CrossRef
  • Nomogram Based on Monocyte-to-Lymphocyte Ratio to Predict Survival of Unresectable Esophageal Squamous Cell Carcinoma Who Receive First-Line PD-1/PD-L1 Inhibitors Combined with Chemotherapy
    Xiaolu Ma, Yongfeng Ding, Jiong Qian, Mingyu Wan, Ning Li, Chenyu Mao, Cheng Xiao, Haiping Jiang, Yulong Zheng, Luntao Wu, Xiaoyu Chen, Nong Xu
    Current Oncology.2022; 29(11): 8937.     CrossRef
  • 8,419 View
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  • 21 Web of Science
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Phase II Study of Induction Chemotherapy with Docetaxel, Capecitabine, and Cisplatin Plus Bevacizumab for Initially Unresectable Gastric Cancer with Invasion of Adjacent Organs or Paraaortic Lymph Node Metastasis
Jwa Hoon Kim, Sook Ryun Park, Min-Hee Ryu, Baek-Yeol Ryoo, Kyu-pyo Kim, Beom Su Kim, Moon-Won Yoo, Jeong Hwan Yook, Byung Sik Kim, Jihun Kim, Sun-Ju Byeon, Yoon-Koo Kang
Cancer Res Treat. 2018;50(2):518-529.   Published online May 24, 2017
DOI: https://doi.org/10.4143/crt.2017.005
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate the efficacy and safety of induction chemotherapy with docetaxel, capecitabine, and cisplatin (DXP) plus bevacizumab (BEV) on initially unresectable locally advanced gastric cancer (LAGC) or paraaortic lymph node (PAN) metastatic gastric cancer (GC).
Materials and Methods
Patients with LAGC or unresectable PAN metastatic GC received six induction chemotherapy cycles (60 mg/m2 docetaxel intravenously on day 1, 937.5 mg/m2 capecitabine orally twice daily on days 1-14, 60 mg/m2 cisplatin intravenously on day 1, and 7.5 mg/kg BEV intravenously on day 1 every 3 weeks), followed by conversion surgery. The primary endpoint was R0 resection rate.
Results
Thirty-one patients with invasion to adjacent organs but without PAN metastasis (n=14, LAGC group) or with PAN metastasis regardless of invasion (n=17, PAN group) were enrolled between July 2010 and December 2014. Twenty-seven patients (87.1%) completed six chemotherapy cycles. The most common grade ≥ 3 toxicities were neutropenia (71%), neutropenia with fever/infection (22.6%/3.2%), and stomatitis (16.1%). The clinical response and R0 resection rates were 64.3% (95% confidence interval [CI], 46.6 to 82.0) and 64.5% (LAGC group, 71.4%; PAN group, 58.8%), respectively. The pathological complete regression rate was 12.9%. After a median follow-up of 44.5 months (range, 39.4 to 49.7 months), the median progression-free survival and overall survival were 13.1 months (95% CI, 8.9 to 17.3) and 38.6 months (95% CI, 22.0 to 55.1), respectively.
Conclusion
Induction chemotherapy with DXP+BEV displayed antitumor activities with encouraging R0 resection rate and manageable toxicity profiles on patients with LAGC or PAN metastatic GC.

Citations

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    Liang Wang, Wei Li, Ya-Gang Liu, Cui Zhang, Wei-Na Gao, Li-Fei Gao, Wei long Zhong
    Journal of Oncology.2022; 2022: 1.     CrossRef
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  • 312 Download
  • 11 Web of Science
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A Multicenter Randomized Phase II Study of Docetaxel vs. Docetaxel Plus Cisplatin vs. Docetaxel Plus S-1 as Second-Line Chemotherapy in Metastatic Gastric Cancer Patients Who Had Progressed after Cisplatin Plus Either S-1 or Capecitabine
Keun-Wook Lee, Bum Jun Kim, Mi-Jung Kim, Hye Sook Han, Jin Won Kim, Young Iee Park, Sook Ryun Park
Cancer Res Treat. 2017;49(3):706-716.   Published online October 18, 2016
DOI: https://doi.org/10.4143/crt.2016.216
AbstractAbstract PDFPubReaderePub
Purpose
This study evaluated the re-challenge of S-1 or cisplatin in combination with docetaxel in metastatic gastric cancer (MGC) that had progressed on a cisplatin plus either S-1 or capecitabine regimen.
Materials and Methods
Patients with progressive disease after first-line cisplatin plus S-1 or capecitabine were randomized to receive 3-week cycles of docetaxel 75 mg/m2 intravenously (IV) on D1 (D), docetaxel 60 mg/m2 IV plus cisplatin 60 mg/m² IV on D1 (DC), or docetaxel 60 mg/m2 IV D1 plus oral S-1 30 mg/m2 twice a day on D1-14 (DS).
Results
Seventy-two patients were randomized to the D (n=23), DC (n=24), or DS (n=25) group. The confirmed response rate was 4.3% (95% confidence interval [CI], 0% to 12.6%), 4.3% (95% CI, 0% to 12.6%), and 8.7% (95% CI, 0% to 20.2%) for the D, DC, and DS groups, respectively. Compared to the D arm, the DS arm had a better progression-free survival (2.7 months vs. 1.3 months, p=0.034) without any deterioration in safety or quality of life, whereas the DC arm had a similar progression-free survival (1.8 months vs. 1.3 months, p=0.804) and poorer overall survival (5.6 months vs. 10.0 months, p=0.035).
Conclusion
A re-challenge with S-1, but not cisplatin, in combination with docetaxel has potential anticancer benefits over docetaxel alone in MGC with progression after prior cisplatin plus S-1 or capecitabine.

Citations

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  • Network Meta-analysis of Randomized Controlled Trials in Patients with Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer: Comparisons Involving Ramucirumab
    Yulia D’yachkova, Astra M. Liepa, Rajat Goel, Veronika Earley-Valovic, Abby Paine, Palvi Gupta, Kaisa Taipale
    Journal of Gastrointestinal Cancer.2025;[Epub]     CrossRef
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    Hui-Fen Lv, Li-Feng Qin, Rui-Zhi Ran, Xue-Ping Jiang, Fang-Yu Zhao, Bo Li
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
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    J. Hack, S.J. Crabb
    Clinical Oncology.2022; 34(8): e329.     CrossRef
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Efficacy and Safety of Regorafenib in Korean Patients with Advanced Gastrointestinal Stromal Tumor after Failure of Imatinib and Sunitinib: A Multicenter Study Based on the Management Access Program
Myoung Kyun Son, Min-Hee Ryu, Joon Oh Park, Seock-Ah Im, Tae-Yong Kim, Su Jin Lee, Baek-Yeol Ryoo, Sook Ryun Park, Yoon-Koo Kang
Cancer Res Treat. 2017;49(2):350-357.   Published online July 19, 2016
DOI: https://doi.org/10.4143/crt.2016.067
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study was to confirm the efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors (GISTs) reported in the GRID phase III trial in Korean patients.
Materials and Methods
Fifty-seven Korean patientswith advanced GISTwho experienced both imatinib and sunitinib failure were enrolled in the management access program between December 2012 and November 2013 and treated with regorafenib (160 mg orally once daily in a 3 weeks on /1 week off).
Results
None of the patients achieved a complete or partial response while 25 patients (44%) showed stable disease for ≥ 12 weeks. With a median follow-up of 12.7 months (range, 0.2 to 27.6 months), the median progression-free survival and overall survival were 4.5 months (95% confidence interval [CI], 3.8 to 5.3) and 12.9 months (95% CI, 8.1 to 17.7), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of their cancer-related symptoms (abdominal pain in eight and abdominal distension in five) during the rest period for regorafenib, but all were ameliorated upon the resumption of regorafenib. The most common grade 3 or 4 adverse event was a hand-foot skin reaction (25%). The regorafenib dose was reduced in 44 patients (77%) due to toxicity, which manifested mainly as a handfoot skin reaction (n=31).
Conclusion
This study confirmed the efficacy and safety of regorafenib for advanced GIST after imatinib and sunitinib failure in Korean patients. Considering the exacerbation of the cancer-related symptoms observed during the rest periods, further exploration of the continuous dosing schedule of regorafenib is warranted in future clinical trials.

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Severe Imatinib-Associated Skin Rash in Gastrointestinal Stromal Tumor Patients: Management and Clinical Implications
Sook Ryun Park, Min-Hee Ryu, Baek-Yeol Ryoo, Mo Youl Beck, In Soon Lee, Mi Jung Choi, Mi Woo Lee, Yoon-Koo Kang
Cancer Res Treat. 2016;48(1):162-170.   Published online September 1, 2015
DOI: https://doi.org/10.4143/crt.2015.017
AbstractAbstract PDFPubReaderePub
Purpose
This study evaluated the incidence of imatinib-associated skin rash, the interventional outcomes of severe rash, and impact of severe rash on the outcomes of imatinib treatment in gastrointestinal stromal tumor (GIST) patients.
Materials and Methods
A total of 620 patients were administered adjuvant or palliative imatinib for GIST at Asan Medical Center between January 2000 and July 2012. This analysis focused on a group of 42 patients who developed a severe rash requiring major interventions, defined as dose interruption or reduction of imatinib or systemic steroid use.
Results
Of the 620 patients treated with imatinib, 148 patients (23.9%) developed an imatinibassociated skin rash; 42 patients (6.8%) developed a severe rash requiring major intervention. Of these, 28 patients (66.8%) successfully continued imatinib with interventions. Serial blood eosinophil levels during imatinib treatment were associated with skin rash and severity. A significant association was observed between successful intervention and blood eosinophil level at the time of intervention initiation. In metastatic settings, patients with severe rash requiring major interventions tended to show poorer progression-free survival than patients who did not require major intervention and patients with no rash, although this finding was not statistically significant (p=0.326).
Conclusion
By aggressive treatment of severe rash through modification of imatinib dose or use of systemic steroid, the majority of patients can continue on imatinib. In particular, imatinib dose intensity can be maintained with use of systemic steroid. Measuring the blood eosinophil levels may be helpful in guiding the management plan for skin rash regarding the intensity and duration of interventions.

Citations

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    Albina N. Khlebnikova, Valentina E. Shikina, Gayane E. Bagramova
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    Deborah van de Wal, Mai Elie, Axel Le Cesne, Elena Fumagalli, Dide den Hollander, Robin L. Jones, Gloria Marquina, Neeltje Steeghs, Winette T. A. van der Graaf, Olga Husson
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    Eo Jin Kim, Min-Hee Ryu, Sook Ryun Park, Mo Youl Beck, Woo Jin Lee, Mi Woo Lee, Yoon-Koo Kang
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    Andrew Hwang, Andrew Iskandar, Michael del Rosario, Constantin A Dasanu
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    Jwa Hoon Kim, Min‐Hee Ryu, Changhoon Yoo, Heejung Chae, Hana Na, Moyoul Beck, Beom Su Kim, Moon‐Won Yoo, Jeong Hwan Yook, Byung Sik Kim, Ki‐Hun Kim, Chan Wook Kim, Yoon‐Koo Kang
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Phase I Study of Axitinib in Combination with Cisplatin and Capecitabine in Patients with Previously Untreated Advanced Gastric Cancer
Do-Youn Oh, Toshihiko Doi, Kuniaki Shirao, Keun-Wook Lee, Sook Ryun Park, Ying Chen, Liqiang Yang, Olga Valota, Yung-Jue Bang
Cancer Res Treat. 2015;47(4):687-696.   Published online February 12, 2015
DOI: https://doi.org/10.4143/crt.2014.225
AbstractAbstract PDFPubReaderePub
Purpose
This phase I trial evaluated the question of whether the standard starting dose of axitinib could be administered in combination with therapeutic doses of cisplatin/capecitabine in patients with previously untreated advanced gastric cancer, and assessed overall safety, pharmacokinetics, and preliminary antitumor activity of this combination.
Materials and Methods
Patients in dose level (DL) 1 received axitinib 5 mg twice a day (days 1 to 21) with cisplatin 80 mg/m2 (day 1) and capecitabine 1,000 mg/m2 twice a day (days 1 to 14) in 21-day cycles. Maximum tolerated dose (MTD) was the highest dose at which ≤ 30% of the first 12 patients experienced a dose-limiting toxicity (DLT) during cycle 1. Ten additional patients were enrolled and treated at the MTD in order to obtain additional safety and pharmacokinetic data.
Results
Three DLTs occurred during cycle 1 in three (25%) of the first 12 patients: ruptured abdominal aortic aneurysm, acute renal failure, and > 5 consecutive days of missed axitinib due to thrombocytopenia. DL1 was established as the MTD, since higher DL cohorts were not planned. Common grade 3/4 non-hematologic adverse events in 22 patients treated at DL1 included hypertension (36.4%) and decreased appetite and stomatitis (18.2% each). Cisplatin/capecitabine slightly increased axitinib exposure; axitinib decreased capecitabine and 5-fluorouracil exposure. Eight patients (36.4%) each had partial response or stable disease. Median response duration was 9.1 months; median progression-free survival was 3.8 months.
Conclusion
In patients with advanced gastric cancer, standard doses of axitinib plus therapeutic doses of cisplatin and capecitabine could be administered in combination. Adverse events were manageable.

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Open-label, Randomized Comparison of the Efficacy of Intravenous Dolasetron Mesylate and Ondansetron in the Prevention of Acute and Delayed Cisplatin-induced Emesis in Cancer Patients
Jin-Soo Kim, Ji Yeon Baek, Sook Ryun Park, In Sil Choi, Sang-Il Kim, Dong-Wan Kim, Seock-Ah Im, Tae-You Kim, Dae Seog Heo, Yung-Jue Bang, Noe Kyeong Kim
Cancer Res Treat. 2004;36(6):372-376.   Published online December 31, 2004
DOI: https://doi.org/10.4143/crt.2004.36.6.372
AbstractAbstract PDFPubReaderePub
Purpose

The aim of this study is to compare the antiemetic efficacy and tolerability of intravenous dolasetron mesylate and ondansetron in the prevention of acute and delayed emesis.

Material and Methods

From April 2002 through October 2002, a total of 112 patients receiving cisplatin- based combination chemotherapy were randomized to receive a single i.v. dose of dolasetron 100 mg or ondansetron 8 mg, 30 minutes before the initiation of chemotherapy. In the ondansetron group, two additional doses of ondansetron 8 mg were given at intervals of 2 to 4 hours. To prevent delayed emesis, dolasetron 200 mg p.o. daily or ondansetron 8 mg p.o. bid was administered from the 2nd days to a maximum of 5 days. The primary end point was the proportion of patients that experienced no emetic episodes and required no rescue medication (complete response, CR) during the 24 hours (acute period) and during Day 2 to Day 5±2 days (delayed period), after chemotherapy. The secondary end points included the incidence and severity of emesis.

Results

105 patients were evaluable for efficacy. CR rates during the acute period were 36.0% for a single dose of dolasetron 100 mg, and 43.6% for three doses of ondansetron 8 mg. CR rates during the delayed period were 8.0% and 10.9%, respectively. There was no significant difference in the efficacy between the two groups. Adverse effects were mostly mild to moderate and not related to study medication.

Conclusions

A single i.v. dose of dolasetron 100 mg is as effective as three i.v. doses of ondansetron 8 mg in preventing acute and delayed emesis after cisplatin-based chemotherapy, with a comparable safety profile.

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    Giovana Paula Rezende Simino, Lays Pires Marra, Eli Iola Gurgel de Andrade, Francisco de Assis Acúrcio, Ilka Afonso Reis, Vânia Eloisa De Araújo, Mariângela Leal Cherchiglia
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