Cancer Research and Treatment

Original Articles

Genitourinary cancer

PD-L1 Upregulation by the mTOR Pathway in VEGFR-TKI–Resistant Metastatic Clear Cell Renal Cell Carcinoma: Se Un Jeong, Hee Sang Hwang, Ja-Min Park, Sun Young Yoon, Su-Jin Shin, Heounjeong Go, Jae-Lyun Lee, Gowun Jeong, Yong Mee Cho; Cancer Res Treat. 2023;55(1):231-244. Published online March 2, 2022; DOI: https://doi.org/10.4143/crt.2021.1526

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Purpose
Tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor receptor (VEGFR) signaling pathways have been used for metastatic clear cell renal cell carcinoma (mCCRCC), but resistance to the drug develops in most patients. We aimed to explore the underlying mechanism of the TKI resistance with regard to programmed death-ligand 1 (PD-L1) and to investigate signaling pathway associated with the resistant mechanism.
Materials and Methods
To determine the mechanism of resistance, 10 mCCRCC patients from whom tumor tissues were harvested at both the pretreatment and the TKI-resistant post-treatment period were included as the discovery cohort, and their global gene expression profiles were compared. A TKI-resistant renal cancer cell line was established by long-term treatment with sunitinib.
Results
Among differentially expressed genes in the discovery cohort, increased PD-L1 expression in post-treatment tissues was noted in four patients. Pathway analysis showed that PD-L1 expression was positively correlated with the mammalian target of rapamycin (mTOR) signaling pathway. The TKI-resistant renal cancer cells showed increased expression of PD-L1 and mTOR signaling proteins and demonstrated aggressive tumoral behaviour. Treatment with mTOR inhibitors down-regulated PD-L1 expression and suppressed aggressive tumoral behaviour, which was reversed with stimulation of the mTOR pathway.
Conclusion
These results showed that PD-L1 expression may be increased in a subset of VEGFR-TKI–resistant mCCRCC patients via the mTOR pathway.

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IFITM3-mediated activation of TRAF6/MAPK/AP-1 pathways induces acquired TKI resistance in clear cell renal cell carcinoma
Se Un Jeong, Ja-Min Park, Sun Young Yoon, Hee Sang Hwang, Heounjeong Go, Dong-Myung Shin, Hyein Ju, Chang Ohk Sung, Jae-Lyun Lee, Gowun Jeong, Yong Mee Cho
Investigative and Clinical Urology.2024; 65(1): 84. CrossRef
Targeting apoptosis in clear cell renal cell carcinoma
Adam Kowalewski, Jędrzej Borowczak, Mateusz Maniewski, Karol Gostomczyk, Dariusz Grzanka, Łukasz Szylberg
Biomedicine & Pharmacotherapy.2024; 175: 116805. CrossRef
Therapeutic advances of targeting receptor tyrosine kinases in cancer
Ciprian Tomuleasa, Adrian-Bogdan Tigu, Raluca Munteanu, Cristian-Silviu Moldovan, David Kegyes, Anca Onaciu, Diana Gulei, Gabriel Ghiaur, Hermann Einsele, Carlo M. Croce
Signal Transduction and Targeted Therapy.2024;[Epub] CrossRef
Mechanisms of sunitinib resistance in renal cell carcinoma and associated opportunities for therapeutics
Yunxia Wang, Xiaolin Liu, Luyao Gong, Weihong Ding, Wenjing Hao, Yeheng Peng, Jun Zhang, Weimin Cai, Yuan Gao
British Journal of Pharmacology.2023; 180(23): 2937. CrossRef
Prior Anti-Angiogenic TKI-Based Treatment as Potential Predisposing Factor to Nivolumab-Mediated Recurrent Thyroid Disorder Adverse Events in mRCC Patients: A Case Series
Luigi Liguori, Angelo Luciano, Giovanna Polcaro, Alessandro Ottaiano, Marco Cascella, Francesco Perri, Stefano Pepe, Francesco Sabbatino
Biomedicines.2023; 11(11): 2974. CrossRef

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Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer: Changhoon Yoo, Boram Han, Hyeong Su Kim, Kyu-pyo Kim, Deokhoon Kim, Jae Ho Jeong, Jae-Lyun Lee, Tae Won Kim, Jung Han Kim, Dae Ro Choi, Hong Il Ha, Jinwon Seo, Heung-Moon Chang, Baek-Yeol Ryoo, Dae Young Zang; Cancer Res Treat. 2018;50(4):1324-1330. Published online January 8, 2018; DOI: https://doi.org/10.4143/crt.2017.526

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Purpose
Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC.
Materials and Methods
Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m² oxaliplatin (day 1), 135 mg/m² irinotecan (day 1), and 40 mg/m² S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue.
Results
In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07).
Conclusion
OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.

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A phase 1 study of biweekly nab-paclitaxel/oxaliplatin/S-1/LV for advanced upper gastrointestinal cancers: TCOG T1216 study
Hui-Jen Tsai, Shih-Hung Yang, Chin-Fu Hsiao, Hsiang-Fong Kao, Yung-Yeh Su, Yan-Shen Shan, Chia-Jui Yen, Jeng-Shiun Du, Chiun Hsu, I-Chen Wu, Li-Tzong Chen
The Oncologist.2024; 29(10): e1396. CrossRef
Liposomal irinotecan, oxaliplatin, and S-1 as first-line therapy for patients with locally advanced or metastatic pancreatic adenocarcinoma (NASOX): A multicenter phase I/IIa study
Hyehyun Jeong, Bum Jun Kim, Choong-kun Lee, Inkeun Park, Dae Young Zang, Hye Jin Choi, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dongwook Oh, Sung-Hoon Moon, Kyu-pyo Kim, Zev Wainberg, Baek-Yeol Ryoo, Changhoon Yoo
European Journal of Cancer.2024; 208: 114194. CrossRef
Redox-responsive engineered hybrid nanomedicine for gallbladder cancer therapy via hyaluronic acid depletion
Jinglin Zou, Cong Jiang, Xianglong Li, Tianyu Zhong, Shuqi Wang, Bo Wang, Dapeng Zhang, Ji-Na Hao, Yuanyuan Cao, Mengjia Guan, Peng Zhang, Bin Dai, Yongsheng Li
Applied Materials Today.2023; 30: 101707. CrossRef
Optimizing Patient Pathways in Advanced Biliary Tract Cancers: Recent Advances and a French Perspective
Cindy Neuzillet, Pascal Artru, Eric Assenat, Julien Edeline, Xavier Adhoute, Jean-Christophe Sabourin, Anthony Turpin, Romain Coriat, David Malka
Targeted Oncology.2023; 18(1): 51. CrossRef
Neoadjuvant Therapy for Extrahepatic Biliary Tract Cancer: A Propensity Score-Matched Survival Analysis
Junya Toyoda, Kota Sahara, Tomoaki Takahashi, Kentaro Miyake, Yasuhiro Yabushita, Yu Sawada, Yuki Homma, Ryusei Matsuyama, Itaru Endo, Timothy Pawlik
Journal of Clinical Medicine.2023; 12(7): 2654. CrossRef
Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study
Jean marc Phelip, Jérôme Desrame, Julien Edeline, Emilie Barbier, Eric Terrebonne, Pierre Michel, Hervé Perrier, Laetitia Dahan, Vincent Bourgeois, Faiza Khemissa Akouz, Emilie Soularue, Valérie Lebrun Ly, Yann Molin, Thierry Lecomte, François Ghiringhell
Journal of Clinical Oncology.2022; 40(3): 262. CrossRef
Early Recurrence in Resected Gallbladder Carcinoma: Clinical Impact and Its Preoperative Predictive Score
Yuji Shimizu, Ryo Ashida, Teiichi Sugiura, Yukiyasu Okamura, Katsuhisa Ohgi, Mihoko Yamada, Shimpei Otsuka, Takeshi Aramaki, Akifumi Notsu, Katsuhiko Uesaka
Annals of Surgical Oncology.2022; 29(9): 5447. CrossRef
Efficacy and safety of modified FOLFIRINOX as salvage therapy for patients with refractory advanced biliary tract cancer: a retrospective study
Liu-Fang Ye, Chao Ren, Long Bai, Jie-Ying Liang, Ming-Tao Hu, Hui Yang, Zhi-Qiang Wang, Feng-Hua Wang, Rui-Hua Xu, Yu-Hong Li, De-Shen Wang
Investigational New Drugs.2021; 39(3): 836. CrossRef
Current Status and Future Perspectives of Perioperative Therapy for Resectable Biliary Tract Cancer: A Multidisciplinary Review
Changhoon Yoo, Sang Hyun Shin, Joon-Oh Park, Kyu-Pyo Kim, Jae Ho Jeong, Baek-Yeol Ryoo, Woohyung Lee, Ki-Byung Song, Dae-Wook Hwang, Jin-hong Park, Jae Hoon Lee
Cancers.2021; 13(7): 1647. CrossRef
Chemotherapy for advanced gallbladder cancer (GBC): A systematic review and meta-analysis
Alexander A. Azizi, Angela Lamarca, Mairéad G. McNamara, Juan W. Valle
Critical Reviews in Oncology/Hematology.2021; 163: 103328. CrossRef
Modified FOLFIRINOX versus gemcitabine plus oxaliplatin as first-line chemotherapy for patients with locally advanced or metastatic cholangiocarcinoma: a retrospective comparative study
Lu Zou, Xuechuan Li, Xiangsong Wu, Jiujie Cui, Xuya Cui, Xiaoling Song, Tai Ren, Xusheng Han, Yidi Zhu, Huaifeng Li, Wenguang Wu, Xu’an Wang, Wei Gong, Liwei Wang, Maolan Li, Wan Yee Lau, Yingbin Liu
BMC Cancer.2021;[Epub] CrossRef
A Novel Combination of Bevacizumab with Chemotherapy Improves Therapeutic Effects for Advanced Biliary Tract Cancer: A Retrospective, Observational Study
Sung-Nan Pei, Chun-Kai Liao, Yaw-Sen Chen, Cheng-Hao Tseng, Chao-Ming Hung, Chong-Chi Chiu, Meng-Che Hsieh, Yu-Fen Tsai, Hsiu-Yun Liao, Wei-Ching Liu, Kun-Ming Rau
Cancers.2021; 13(15): 3831. CrossRef
Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study
Changhoon Yoo, Kyu-pyo Kim, Jae Ho Jeong, Ilhwan Kim, Myoung Joo Kang, Jaekyung Cheon, Byung Woog Kang, Hyewon Ryu, Ji Sung Lee, Kyung Won Kim, Ghassan K Abou-Alfa, Baek-Yeol Ryoo
The Lancet Oncology.2021; 22(11): 1560. CrossRef
Efficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: an open-label, single arm, phase 2 trial
Ali Belkouz, Judith de Vos-Geelen, Ron A. A. Mathôt, Ferry A. L. M. Eskens, Thomas M. van Gulik, Martijn G. H. van Oijen, Cornelis J. A. Punt, Johanna W. Wilmink, Heinz-Josef Klümpen
British Journal of Cancer.2020; 122(5): 634. CrossRef
miR‐373 inhibits autophagy and further promotes apoptosis of cholangiocarcinoma cells by targeting ULK1
Pin Lv, Yi‐Fan Luo, Wen‐Yi Zhou, Ben Liu, Zheng Zhou, Yong‐Zhong Shi, Ren Huang, Chuang Peng, Zi‐Li He, Jun Wang, Hong‐Hui Zhang, Sheng‐Dan Nie
The Kaohsiung Journal of Medical Sciences.2020; 36(6): 429. CrossRef
Advances in adjuvant therapy of biliary tract cancer: an overview of current clinical evidence based on phase II and III trials
A. Belkouz, J.W. Wilmink, N. Haj Mohammad, J. Hagendoorn, J. de Vos-Geelen, C.H.C. Dejong, M.Y.V. Homs, B. Groot Koerkamp, T.M. van Gulik, M.G.H. van Oijen, C.J.A. Punt, H. Klümpen
Critical Reviews in Oncology/Hematology.2020; 151: 102975. CrossRef
A retrospective study of patient-tailored FOLFIRINOX as a first-line chemotherapy for patients with advanced biliary tract cancer
Ayhan Ulusakarya, Abdoulaye Karaboué, Oriana Ciacio, Gabriella Pittau, Mazen Haydar, Pamela Biondani, Yusuf Gumus, Amale Chebib, Wathek Almohamad, Pasquale F. Innominato
BMC Cancer.2020;[Epub] CrossRef
Overview of current targeted therapy in gallbladder cancer
Xiaoling Song, Yunping Hu, Yongsheng Li, Rong Shao, Fatao Liu, Yingbin Liu
Signal Transduction and Targeted Therapy.2020;[Epub] CrossRef
Irinotecan combined with oxaliplatin and S-1 in patients with metastatic pancreatic adenocarcinoma: a single-arm, three-centre, prospective study
Keke Nie, Ling Zhang, Yunhong You, Hongmei Li, Xiuhui Guo, Zhongfa Zhang, Chunling Zhang, Youxin Ji
Therapeutic Advances in Medical Oncology.2020;[Epub] CrossRef
The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: A meta-analysis and systematic review
Ming-Liang Wang, Zhang-Yan Ke, Shuai Yin, Chen-Hai Liu, Qiang Huang
Hepatobiliary & Pancreatic Diseases International.2019; 18(2): 110. CrossRef
Nal-IRI with 5-fluorouracil (5-FU) and leucovorin or gemcitabine plus cisplatin in advanced biliary tract cancer - the NIFE trial (AIO-YMO HEP-0315) an open label, non-comparative, randomized, multicenter phase II study
L. Perkhofer, A. W. Berger, A. K. Beutel, E. Gallmeier, S. Angermeier, L. Fischer von Weikersthal, T. O. Goetze, R. Muche, T. Seufferlein, T. J. Ettrich
BMC Cancer.2019;[Epub] CrossRef

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Pazopanib for the Treatment of Non-clear Cell Renal Cell Carcinoma: A Single-Arm, Open-Label, Multicenter, Phase II Study: Ki Sun Jung, Su Jin Lee, Se Hoon Park, Jae-Lyun Lee, Se-Hoon Lee, Jae Yun Lim, Jung Hun Kang, Suee Lee, Sun Young Rha, Kyung Hee Lee, Ho Young Kim, Ho Yeong Lim; Cancer Res Treat. 2018;50(2):488-494. Published online May 22, 2017; DOI: https://doi.org/10.4143/crt.2016.584

Abstract PDF Supplementary Material PubReader ePub

Purpose
The optimal treatment strategy for patients with metastatic non-clear cell type renal cell carcinoma (nccRCC) remains unclear. Although several inhibitors of vascular endothelial growth factor have recently shown efficacy against nccRCC, the clinical benefit of pazopanib in nccRCC has not been analyzed. We therefore designed a single-arm, open-label, phase II study to determine the efficacy and safety of pazopanib in patients with nccRCC.
Materials and Methods
Patientswith locally advanced or metastatic nccRCC, exceptfor collecting duct or sarcomatoid type, received 800 mg/day of pazopanib daily until progression of disease or intolerable toxicity. One cyclewas defined as 4weeks and tumorresponsewas evaluated every two cycles. The primary objective was overall response rate (ORR).
Results
A total of 29 eligible patients were enrolled at nine centers in Korea from December 2012 and September 2014. The median age of the patients was 58 years (range, 27 to 76 years) and 21 patients (72%) were male. Regarding histology type, 19 patients had papillary, three had chromophobe, two had unclassified and five had unknown non-clear cell type. Of 28 evaluable patients, eight achieved a confirmed partial response with ORR of 28%. The median progression-free survival was 16.5 months (95% confidence interval, 10.9 to 22.1) and median overall survival was not reached. Sixteen patients (55%) experienced treatment-related toxicity of grade 3 or more, but most adverse events were overcome through dose reduction and delay.
Conclusion
In this prospective phase II study, pazopanib demonstrated promising activity and tolerable safety profile in patients with metastatic nccRCC.

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Papillary Renal Cell Carcinoma: Current Evidence and Future Directions
Albert Jang, Charbel S. Hobeika, Shilpa Gupta
Kidney Cancer.2024; 8(1): 61. CrossRef
Comparison of the efficacy of sunitinib and pazopanib in patients with advanced non-clear renal cell carcinoma
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Efficacy of Chemotherapy in Patients with Unresectable or Metastatic Pancreatic Acinar Cell Carcinoma: Potentially Improved Efficacy with Oxaliplatin-Containing Regimen: Changhoon Yoo, Bum Jun Kim, Kyu-pyo Kim, Jae-Lyun Lee, Tae Won Kim, Baek-Yeol Ryoo, Heung-Moon Chang; Cancer Res Treat. 2017;49(3):759-765. Published online November 9, 2016; DOI: https://doi.org/10.4143/crt.2016.371

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pancreatic acinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas. Because of its rare incidence, the efficacy of chemotherapy in this patient population has been largely unknown. Therefore, we retrospectively analyzed the outcomes of patients with advanced pancreatic ACC who received chemotherapy.
Materials and Methods
Between January 1997 and March 2015, 15 patients with unresectable or metastatic pancreatic ACC who received systemic chemotherapy were identified in Asan Medical Center, Korea.
Results
The median age was 58 years. Eleven and four patients had recurrent/metastatic and locally advanced unresectable disease. The median overall survival in all patients was 20.9 months (95% confidence interval [CI], 15.7 to 26.1). As first-line therapy, intravenous 5-fluorouracil were administered in four patients (27%), gemcitabine in five (33%), gemcitabine plus capecitabine in two (13%), oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) in two (13%), and concurrent chemoradiotherapy followed by capecitabine maintenance therapy in two (13%). The objective response rate (ORR) to chemotherapy alone was 23% and the median progression-free survival (PFS) was 5.6 months (95% CI, 2.8 to 8.4). After progression, second- line chemotherapy was administered in eight patients, while four patients received FOLFOX and the other four patients received gemcitabine. The ORR was 38%, and patients administered FOLFOX had significantly better PFS than those administered gemcitabine (median, 6.5 months vs. 1.4 months; p=0.007). The ratio of time to tumor progression (TTP) during first-line chemotherapy to TTP at second-line chemotherapy was significantly higher in patients administered FOLFOX (4.07; range, 0.87 to 8.30) than in those administered gemcitabine (0.12; range, 0.08 to 0.25; p=0.029).
Conclusion
Our results suggest that oxaliplatin-containing regimens may have improved activity against pancreatic ACC.

Citations

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Comprehensive review of pancreatic acinar cell carcinoma: epidemiology, diagnosis, molecular features and treatment
Kenji Ikezawa, Makiko Urabe, Yugo Kai, Ryoji Takada, Hirofumi Akita, Shigenori Nagata, Kazuyoshi Ohkawa
Japanese Journal of Clinical Oncology.2024; 54(3): 271. CrossRef
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Katsuhito Teramatsu, Nao Fujimori, Masatoshi Murakami, Sho Yasumori, Kazuhide Matsumoto, Kohei Nakata, Masafumi Nakamura, Yutaka Koga, Yoshinao Oda, Yoshihiro Ogawa
Clinical Journal of Gastroenterology.2024; 17(4): 776. CrossRef
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Use of a High-Throughput Genotyping Platform (OncoMap) for RAS Mutational Analysis to Predict Cetuximab Efficacy in Patients with Metastatic Colorectal Cancer: Dalyong Kim, Yong Sang Hong, Jeong Eun Kim, Kyu-pyo Kim, Jae-Lyun Lee, Sung-Min Chun, Jihun Kim, Se Jin Jang, Tae Won Kim; Cancer Res Treat. 2017;49(1):37-43. Published online April 27, 2016; DOI: https://doi.org/10.4143/crt.2016.069

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Purpose
Cetuximab demonstrates improved efficacy outcomes in patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS exon 2. Resistance to cetuximab is mediated by activating less frequent mutations in the RAS genes beyond KRAS exon 2. We performed extended RASmutational analysis using a high -throughput genotyping platform (OncoMap) and evaluated extended RAS analysis for predicting cetuximab efficacy in patients harboring wild-type KRAS exon 2 tumors following Sanger sequencing.
Materials and Methods
Extended RAS analysis was performed on 227 wild-type KRAS exon 2 mCRC patients who received cetuximab as salvage treatment using OncoMap ver. 4.0. Targeted genes included exon 2, exon 3, and exon 4, both in KRAS and NRAS, and included BRAF exon 15. We assessed efficacy by the new RAS mutation status.
Results
The OncoMap detected 57 additional mutations (25.1%): 25 (11%) in KRAS exon 2 and 32 (14.1%) beyond KRAS exon 2. Survival differences were observed after dividing patients into the wild-type RAS group (n=170) and mutant RAS group (n=57) using OncoMap. Progression-free survival was 4.8 months versus 1.8 months (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.32 to 0.61), and overall survival was 11.9 months versus 8.4 months (HR, 0.65; 95% CI, 0.47 to 0.88).
Conclusion
Sanger sequencing is not sufficient for selecting candidates for cetuximab treatment. High-throughput extended RAS genotyping is a feasible approach for this purpose and identifies patients who might benefit from cetuximab treatment.

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Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik ve Patolojik Özellikleri
Mehmet SEZEN, Murat ARAZ
Uludağ Üniversitesi Tıp Fakültesi Dergisi.2019; 45(2): 131. CrossRef
Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO–ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS
T. Yoshino, D. Arnold, H. Taniguchi, G. Pentheroudakis, K. Yamazaki, R.-H. Xu, T.W. Kim, F. Ismail, I.B. Tan, K.-H. Yeh, A. Grothey, S. Zhang, J.B. Ahn, M.Y. Mastura, D. Chong, L.-T. Chen, S. Kopetz, T. Eguchi-Nakajima, H. Ebi, A. Ohtsu, A. Cervantes, K.
Annals of Oncology.2018; 29(1): 44. CrossRef
Ligand-Independent Epidermal Growth Factor Receptor Overexpression Correlates with Poor Prognosis in Colorectal Cancer
Sumi Yun, Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Hye Seung Lee
Cancer Research and Treatment.2018; 50(4): 1351. CrossRef
Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild-type metastatic colorectal cancer
Dalyong Kim, Sun Young Kim, Ji Sung Lee, Yong Sang Hong, Jeong Eun Kim, Kyu-pyo Kim, Jihun Kim, Se Jin Jang, Young-Kwang Yoon, Tae Won Kim
BMC Gastroenterology.2017;[Epub] CrossRef

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Efficacy and Safety of Everolimus in Korean Patients with Metastatic Renal Cell Carcinoma Following Treatment Failure with a Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor: Kwonoh Park, Jae-Lyun Lee, Jin-Hee Ahn, Kyoo Hyung Lee, In-Gab Jeong, Cheryn Song, Bumsik Hong, Jun Hyuk Hong, Hanjong Ahn; Cancer Res Treat. 2014;46(4):339-347. Published online July 16, 2014; DOI: https://doi.org/10.4143/crt.2013.154

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to assess the efficacy and safety of everolimus in Korean patients with metastatic renal cell carcinoma (mRCC) for whom initial treatment with a vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) has failed. Materials and Methods Eligible patients with mRCC (any histology) who had progressed on or were intolerant of VEGFr-TKI therapy received oral everolimus (10 mg dose once daily). Tumor response was reassessed according to Response Evaluation Criteria in Solid Tumors (RECIST). Results This study included 100 patientswith a median follow-up duration of 10.2 months, a median progression-free survival (PFS) of 4.2 months (95% confidence interval [CI], 3.4 to 5.0 months), and an overall survival of 10.1 months (95% CI, 6.9 to 13.3 months). The most common grade 3 or greater adverse events (AEs) overall were anemia (13%), pneumonitis (9%), hyperglycemia (8%), and stomatitis (6%). While the incidence of pneumonitis was similar (26 cases, 26%) to the reported incidence in Western patients, the Korean presentations were more severe: 10 patients permanently discontinued everolimus due to pneumonitis, including two deaths on treatment. Statistically significant relationships were established between biologic toxicities, hyperglycemia and anemia, and PFS (hyperglycemia vs. non-hyperglycemia: hazard ratio [HR], 0.61; p=0.055 and anemia vs. non-anemia: HR, 0.51; p=0.021). Conclusion Everolimus was effective in Korean patients with mRCC who had failed initial VEGFr-TKI therapy. While everolimus was well tolerated in general and the AE incidence of this study was similar to those of previous reports, severe pneumonitis was common. Hyperglycemia and anemia showed significant correlation with PFS and thus may be potentially useful as prognostic indicators.

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Resistance to Systemic Agents in Renal Cell Carcinoma Predict and Overcome Genomic Strategies Adopted by Tumor
Veronica Mollica, Vincenzo Di Nunno, Lidia Gatto, Matteo Santoni, Marina Scarpelli, Alessia Cimadamore, Antonio Lopez-Beltran, Liang Cheng, Nicola Battelli, Rodolfo Montironi, Francesco Massari
Cancers.2019; 11(6): 830. CrossRef
Oral stomatitis and mTOR inhibitors: A review of current evidence in 20,915 patients
L Lo Muzio, C Arena, G Troiano, A Villa
Oral Diseases.2018; 24(1-2): 144. CrossRef

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Efficacy and Safety of Docetaxel Plus Prednisolone Chemotherapy for Metastatic Hormone-Refractory Prostate Adenocarcinoma: Single Institutional Study in Korea: Jae-Lyun Lee, Jeong Eun Kim, Jin-Hee Ahn, Dae-Ho Lee, Jungshin Lee, Choung-Soo Kim, Jun Hyuk Hong, Bumsik Hong, Cheryn Song, Hanjong Ahn; Cancer Res Treat. 2010;42(1):12-17. Published online March 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.1.12

Abstract PDF PubReader ePub

Purpose

To assess the efficacy and safety of treating Korean patients with metastatic hormone-refractory prostate cancer (HRPC) using docetaxel plus prednisolone chemotherapy.

Materials and Methods

This was a retrospective cohort study performed in 98 patients with metastatic HRPC between October 2003 and April 2008. After screening, 72 patients fit the eligibility criteria for inclusion in this study. Treatment consisted of 5 mg prednisolone twice daily and 75 mg/m² docetaxel once every 3 weeks.

Results

Patient demographic characteristics included: median age 67 years (range, 51~86), median ECOG performance status 1 (0~2), Gleason score ≥8 in 61 patients (86%), and median serum PSA 45.5 ng/mL (range, 3.7~2,420.0). A total of 405 cycles of treatment were administered with a median 6 cycles (range, 1~20) per patient. The median docetaxel dose-intensity was 24.4 mg/m²/week (range, 17.5~25.6). A PSA response was seen in 51% of 63 evaluable patients at 12 weeks and maximal PSA decline ≥50% in 59% of 70 evaluable patients. Tumor response was evaluated in 13 patients, 4 patients achieved PR, and 5 patients had SD with a response rate of 31%. With a median follow-up duration of 23.1 months (95%CI, 16.7~29.5), the median time to PSA progression was 5.1 months (95%CI, 4.5~5.8) and median overall survival was 22.8 months (95%CI, 16.6~29.1). Nine (13%) patients experienced grade 3 or higher febrile neutropenia.

Conclusion

This chemotherapy regimen (docetaxel every 3 weeks plus prednisolone daily) demonstrated a strong response in Korean patients with metastatic HRPC, while the toxicity profile was manageable and similar to that observed in Western patients.

Citations

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Modulation of inflammatory mediators underlies the antitumor effect of the combination of morusin and docetaxel on prostate cancer cells
Sana A. Fadil, Dina A.I. Albadawi, Khalid Z. Alshali, Hossam M. Abdallah, Mona M. Saber
Biomedicine & Pharmacotherapy.2024; 180: 117572. CrossRef
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Kwonoh Park, Jin Young Kim, Inkeun Park, Seong Hoon Shin, Hyo Jin Lee, Jae Lyun Lee
Yonsei Medical Journal.2023; 64(2): 86. CrossRef
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Journal of Cancer Research and Clinical Oncology.2022; 148(3): 727. CrossRef
AN INDIAN PROSPECTIVE STUDY OF DOCETAXEL THERAPY IN CRPC: CAN PRETREATMENT FACTORS PREDICT THE RESPONSE
Devashish Kaushal, Rajeev Sood
INTERNATIONAL JOURNAL OF SCIENTIFIC RESEARCH.2021; : 78. CrossRef
A prospective phase-II trial of biweekly docetaxel plus androgen deprivation therapy in patients with previously-untreated metastatic castration-naïve prostate cancer
Seonggyu Byeon, Hongsik Kim, Hwang Gyun Jeon, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Soon Il Lee, Se Hoon Park
BMC Cancer.2021;[Epub] CrossRef
Efficacy of cisplatin combined with topotecan in patients with advanced or recurrent ovarian cancer as second- or higher-line palliative chemotherapy
Myung-Won Lee, Hyewon Ryu, Ik-Chan Song, Hwan-Jung Yun, Deog-Yeon Jo, Young Bok Ko, Hyo-Jin Lee
Medicine.2020; 99(17): e19931. CrossRef
A retrospective feasibility study of biweekly docetaxel in patients with high-risk metastatic castration-naïve prostate cancer
Sang Eun Yoon, Youjin Kim, Jangho Cho, Minyong Kang, Hyun Hwan Sung, Hwang Gyun Jeon, Byoung Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han Yong Choi, Su Jin Lee, Se Hoon Park
BMC Urology.2019;[Epub] CrossRef
Effect of docetaxel on the regulation of proliferation and apoptosis of human prostate cancer cells
Chongyi Yang, Weijie Zhang, Jie Wang, Pengpeng Chen, Jiangjiang Jin
Molecular Medicine Reports.2019;[Epub] CrossRef
Impact of early changes in serum biomarkers following androgen deprivation therapy on clinical outcomes in metastatic hormone-sensitive prostate cancer
Hiromi Sato, Shintaro Narita, Norihiko Tsuchiya, Atsushi Koizumi, Taketoshi Nara, Sohei Kanda, Kazuyuki Numakura, Hiroshi Tsuruta, Atsushi Maeno, Mitsuru Saito, Takamitsu Inoue, Shigeru Satoh, Kyoko Nomura, Tomonori Habuchi
BMC Urology.2018;[Epub] CrossRef
A retrospective feasibility study of biweekly, reduced-dose docetaxel in Asian patients with castrate-resistant, metastatic prostate cancer
Hae Su Kim, Ji Yun Lee, Su Jin Lee, Ho Yeong Lim, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han-Yong Choi, Se Hoon Park
BMC Urology.2017;[Epub] CrossRef
Clinical Outcomes of Continuous Addition of Androgen Deprivation Therapy During Docetaxel Chemotherapy for Patients With Castration-Resistant Prostate Cancer
Dong Hoon Lee, Jung Ho Kim, Won Ik Seo, Jong Kil Nam, Tae Nam Kim, Cheol Kyu Oh, Soo Dong Kim, Sung-Woo Park, Jae Sung Chung, Sang Hyun Park, Wan Lee, Gyung Tak Sung, Moon Kee Chung, Jae Il Chung
The Korean Journal of Urological Oncology.2017; 15(2): 59. CrossRef
Hormonal therapy and chemotherapy for advanced prostate cancer
Jae Lyun Lee
Journal of the Korean Medical Association.2015; 58(1): 30. CrossRef
Gemcitabine–oxaliplatin plus prednisolone is active in patients with castration-resistant prostate cancer for whom docetaxel-based chemotherapy failed
J-L Lee, J-H Ahn, M K Choi, Y Kim, S-W Hong, K-H Lee, I-G Jeong, C Song, B-S Hong, J H Hong, H Ahn
British Journal of Cancer.2014; 110(10): 2472. CrossRef
Effectiveness and safety of cabazitaxel plus prednisolone chemotherapy for metastatic castration-resistant prostatic carcinoma: data on Korean patients obtained by the cabazitaxel compassionate-use program
Jae-Lyun Lee, Se Hoon Park, Su-Jin Koh, Se Hoon Lee, Yu Jung Kim, Yoon Ji Choi, Jihye Lee, Ho Yeong Lim
Cancer Chemotherapy and Pharmacology.2014; 74(5): 1005. CrossRef
Predictive Factors for Neutropenia after Docetaxel-Based Systemic Chemotherapy in Korean Patients with Castration-Resistant Prostate Cancer
Whi-An Kwon, Tae Hoon Oh, Jae Whan Lee, Seung Chol Park
Asian Pacific Journal of Cancer Prevention.2014; 15(8): 3443. CrossRef
Clinical predictor of survival following docetaxel-based chemotherapy
HSIANG-YING LEE, WEN-JENG WU, CHUN-HSIUNG HUANG, YII-HER CHOU, CHUN-NUNG HUANG, YUNG-CHIN LEE, KAI-FU YANG, MEI-HUI LEE, SHU-PIN HUANG
Oncology Letters.2014; 8(4): 1788. CrossRef
Prostate-specific antigen response rate of sequential chemotherapy in castration-resistant prostate cancer: the results of real life practice
Geehyun Song, Chunwoo Lee, Dalsan You, In Gab Jeong, Jun Hyuk Hong, Hanjong Ahn, Choung-Soo Kim
Prostate International.2013; 1(3): 125. CrossRef
Quimioterapia sistémica basada en docetaxel en hombres coreanos mayores con cáncer de próstata resistente a la castración
S.C.H. Park, L.J. Whan, R.J. Sik
Actas Urológicas Españolas.2012; 36(7): 425. CrossRef
Docetaxel-based systemic chemotherapy in elderly Korean men with castration-resistant prostate cancer
S.C.H. Park, L.J. Whan, R.J. Sik
Actas Urológicas Españolas (English Edition).2012; 36(7): 425. CrossRef

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Case Report

Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors of the Stomach: Report of Three Cases: Ji Seon Oh, Jae-Lyun Lee, Mi-Jung Kim, Min-Hee Ryu, Heung Moon Chang, Tae Won Kim, Se Jin Jang, Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim, Yoon-Koo Kang; Cancer Res Treat. 2006;38(3):178-183. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.178

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Neoadjuvant imatinib therapy used to treat locally advanced or metastatic gastrointestinal stromal tumors (GI ST) remains under active investigation. We studied three cases of locally advanced gastric GISTs treated with imatinib on a neoadjuvant basis, followed by a complete surgical resection. Three patients were diagnosed with locally advanced unresectable GIST of the stomach and were started on imatinib 400 mg/day. After the imatinib treatment, partial responses were achieved in all patients and the tumors were considered resectable. Surgical resection was done after 7, 11, and 8 months of imatinib therapy, respectively. In one case, a metastatic liver lesion was detected during the imatinib treatment using computed tomography scans, so the imatinib therapy was maintained for 11 months postoperatively. In the other two patients without distant metastasis, imatinib treatment was not restarted after surgery. Mutational analysis revealed a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and PDGFRA in one patient. During pathology review of all three cases, we noted several features common to imatinib treatment. There was no evidence of tumor recurrence in all three patients at respective follow-up visits of 22, 15, and 7 months. These results suggest that the neoadjuvant imatinib therapy is a potentially curative approach for selected patients with locally advanced GIST.

Citations

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Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor
Dong-Hoe Koo, Min-Hee Ryu, Kyoung-Mee Kim, Han-Kwang Yang, Akira Sawaki, Seiichi Hirota, Jie Zheng, Bo Zhang, Chin-Yuan Tzen, Chun-Nan Yeh, Toshirou Nishida, Lin Shen, Li-Tzong Chen, Yoon-Koo Kang
Cancer Research and Treatment.2016; 48(4): 1155. CrossRef
Correlation between Computed Tomography and Pathological Findings of Gastrointestinal Stromal Tumors Treated with Imatinib Mesylate
Ki Choon Sim, Beom Jin Park, Na Yeon Han, Deuk Jae Sung, Min Ju Kim, Sung Bum Cho, Hyun Kwon Ha, Hyoung Rae Kim
Journal of the Korean Society of Radiology.2014; 71(5): 239. CrossRef
Diagnosis and Treatment of Gastrointestinal Stromal Tumor
Yoon-Koo Kang, Dong Hoe Koo
Korean Journal of Medicine.2013; 85(4): 341. CrossRef
Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea
Yoon-Koo Kang, Hye Jin Kang, Kyoung-Mee Kim, Taesung Sohn, Dongil Choi, Min-Hee Ryu, Woo Ho Kim, Han-Kwang Yang
Cancer Research and Treatment.2012; 44(2): 85. CrossRef
Efficacy of Imatinib Mesylate Neoadjuvant Treatment for a Locally Advanced Rectal Gastrointestinal Stromal Tumor
Kyu Jong Yoon, Nam Kyu Kim, Kang Young Lee, Byung Soh Min, Hyuk Hur, Jeonghyun Kang, Sarah Lee
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Original Article

Efficacy and Safety Study of Docetaxel as Salvage Chemotherapy in Metastatic Gastric Cancer Failing Fluoropyrimidine and Platinum Combination Chemotherapy: Jae-Lyun Lee, Min-Hee Ryu, Heung Moon Chang, Tae-Won Kim, Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim, Jung Shin Lee, Yoon-Koo Kang; Cancer Res Treat. 2005;37(4):201-207. Published online August 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.4.201

Abstract PDF PubReader ePub

Purpose

Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used for the first line treatment of advanced gastric cancer (AGC). Docetaxel (D) has shown promising activity in this disease. The present study retrospectively investigated the efficacy of D monotherapy as salvage chemotherapy for AGC that is failing F and P combination chemotherapy.

Materials and Methods

A total of 34 patients, fitting the eligibility criteria, were included in this study. D was administered at a dose of 75 mg/m² IV every 3 weeks, with dexamethasone prophylaxis. Twenty-nine patients had measurable lesions. The median treatment-free interval was 38.5 days, and 91.2% of patients had progressed within 4 months of withdrawal of the first line chemotherapy.

Results

A total of 133 cycles of D were administered, with a median of 3.5 (1~8) cycles. From an intention-to-treat analysis, 6 patients achieved partial responses (PR), with a response rate of 20.7% (95% CI, 6.0~35.4). The duration of objective PRs in these six were 2.3+, 2.5+, 2.9, 3.0+, 6.2 and 6.8 months, respectively. Six patients showed a stable disease, but 15 showed progression. The median time to progression was 4.2 months (95% CI, 2.8~5.5), with a median overall survival since the start of D monotherapy of 8.4 months (95% CI, 5.5~11.3). Grade 3/4 neutropenia and febrile neutropenia occurred in 12.9% of patients and 3.1% of cycles. The incidence of grade 3 or worse non-hematological toxicities were as follows; peripheral sensory neuropathy 9.7%, asthenia 3.2% and allergic reaction 2.7%.

Conclusion

Docetaxel, 75 mg/m², is active in AGC as second-line chemotherapy after failure of prior exposure to the F and P combination chemotherapy, with a favorable toxicity profile.

Citations

Citations to this article as recorded by

Comparison of adverse events following injection of original or generic docetaxel for the treatment of breast cancer
Nao Tagawa, Erika Sugiyama, Masataka Tajima, Yasutsuna Sasaki, Seigo Nakamura, Hiromi Okuyama, Hisanori Shimizu, Vilasinee Hirunpanich Sato, Tadanori Sasaki, Hitoshi Sato
Cancer Chemotherapy and Pharmacology.2017; 80(4): 841. CrossRef
Efficacy and Safety of Trastuzumab-based Therapy in Combination with Different Chemotherapeutic Regimens in Advanced Esophagogastric Cancer – a Single Cancer-center Experience
Georg-Martin Haag, Leonidas Apostolidis, Dirk Jaeger
Tumori Journal.2014; 100(3): 237. CrossRef
Phase I Dose-Escalation Study of Intravenous Aflibercept in Combination with Docetaxel in Patients with Advanced Solid Tumors
Nicolas Isambert, Gilles Freyer, Sylvie Zanetta, Benoît You, Pierre Fumoleau, Claire Falandry, Laure Favier, Sylvie Assadourian, Karen Soussan-Lazard, Samira Ziti-Ljajic, Veronique Trillet-Lenoir
Clinical Cancer Research.2012; 18(6): 1743. CrossRef
A phase II study of docetaxel as salvage chemotherapy in advanced gastric cancer after failure of fluoropyrimidine and platinum combination chemotherapy
Jae-Lyun Lee, Min-Hee Ryu, Heung Moon Chang, Tae-Won Kim, Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim, Minsun Kim, Young Joo Chun, Jung Shin Lee, Yoon-Koo Kang
Cancer Chemotherapy and Pharmacology.2008; 61(4): 631. CrossRef

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