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7 "Dong-Hoe Koo"
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Gastrointestinal cancer
Varlitinib and Paclitaxel for EGFR/HER2 Co-expressing Advanced Gastric Cancer: A Multicenter Phase Ib/II Study (K-MASTER-13)
Dong-Hoe Koo, Minkyu Jung, Yeul Hong Kim, Hei-Cheul Jeung, Dae Young Zang, Woo Kyun Bae, Hyunki Kim, Hyo Song Kim, Choong-kun Lee, Woo Sun Kwon, Hyun Cheol Chung, Sun Young Rha
Cancer Res Treat. 2024;56(4):1136-1145.   Published online April 29, 2024
DOI: https://doi.org/10.4143/crt.2023.1324
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC).
Materials and Methods
Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity.
Results
RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D.
Conclusion
A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

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  • Unraveling the future: Innovative design strategies and emerging challenges in HER2-targeted tyrosine kinase inhibitors for cancer therapy
    Sixiang Zheng, Ruixian Chen, Lele Zhang, Lun Tan, Lintao Li, Fangyi Long, Ting Wang
    European Journal of Medicinal Chemistry.2024; 276: 116702.     CrossRef
  • 1,551 View
  • 117 Download
  • 1 Web of Science
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A Phase 3 Randomized Clinical Trial to Compare Efficacy and Safety between Combination Therapy and Monotherapy in Elderly Patients with Advanced Gastric Cancer (KCSG ST13-10)
Keun-Wook Lee, Dae Young Zang, Min-Hee Ryu, Hye Sook Han, Ki Hyang Kim, Mi-Jung Kim, Sung Ae Koh, Sung Sook Lee, Dong-Hoe Koo, Yoon Ho Ko, Byeong Seok Sohn, Jin Won Kim, Jin Hyun Park, Byung-Ho Nam, In Sil Choi
Cancer Res Treat. 2023;55(4):1250-1260.   Published online May 25, 2023
DOI: https://doi.org/10.4143/crt.2023.333
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy.
Materials and Methods
Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy.
Results
After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%.
Conclusion
Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.

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  • A prognostic nomogram to predict the cancer-specific survival of patients with initially diagnosed metastatic gastric cancer: a validation study in a Chinese cohort
    Ziming Zhao, Erxun Dai, Bao Jin, Ping Deng, Zulihaer Salehebieke, Bin Han, Rongfan Wu, Zhaowu Yu, Jun Ren
    Clinical and Translational Oncology.2024;[Epub]     CrossRef
  • 3,477 View
  • 292 Download
  • 1 Web of Science
  • 1 Crossref
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General
A Multicenter, Prospective, Observational Study to Evaluate Ethanol-Induced Symptoms in Patients Receiving Docetaxel Chemotherapy
Young-Woong Won, Jin-Hyoung Kang, Jung Hye Kwon, Dong-Hoe Koo, Jung Hun Kang, Chi Hoon Maeng, Hee Kyung Ahn, Sung Yong Oh, Dae-Won Lee, Joohyuk Sohn, So Yeon Oh, Kyung Hee Lee, Su-Jin Koh, Keun Seok Lee, Chan-Kyu Kim, Ji-Yeon Kim, Jun Ho Ji, Sung-Bae Kim, Joo Young Ha, Ho Young Kim
Cancer Res Treat. 2023;55(4):1096-1103.   Published online April 7, 2023
DOI: https://doi.org/10.4143/crt.2022.1565
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Several previous studies and case reports have reported ethanol-induced symptoms in patients receiving anticancer drugs containing ethanol. Most docetaxel formulations contain ethanol as a solvent. However, there are insufficient data on ethanol-induced symptoms when docetaxel-containing ethanol is administered. The primary purpose of this study was to investigate the frequency and pattern of ethanol-induced symptoms during and after docetaxel administration. The secondary purpose was to explore the risk factors for ethanol-induced symptoms.
Materials and Methods
This was a prospective, multicenter, observational study. The participants filled out ethanol-induced symptom questionnaire on the day of chemotherapy and the following day.
Results
Data from 451 patients were analyzed. The overall occurrence rate of ethanol-induced symptoms was 44.3% (200/451 patients). The occurrence rate of facial flushing was highest at 19.7% (89/451 patients), followed by nausea in 18.2% (82/451 patients), and dizziness in 17.5% (79/451 patients). Although infrequent, unsteady walking and impaired balance occurred in 4.2% and 3.3% of patients, respectively. Female sex, presence of underlying disease, younger age, docetaxel dose, and docetaxel-containing ethanol amount were significantly associated with the occurrence of ethanol-induced symptoms.
Conclusion
The occurrence of ethanol-induced symptoms was not low in patients receiving docetaxel-containing ethanol. Physicians need to pay more attention to the occurrence of ethanol-induced symptoms and prescribe ethanol-free or low-ethanol-containing formulations to high-risk patients.

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  • Evaluation of self-assembling properties of paclitaxel-biotin conjugates
    Dmitry V. Beigulenko, Anna Yu. Belyaeva, Ekaterina S. Kazakova, Maria M. Antonova, Aleksander S. Peregudov, Aleksey A. Nikitin, Tatyana S. Kovshova, Yulia V. Ermolenko, Konstantin A. Kochetkov
    Nano-Structures & Nano-Objects.2024; 40: 101375.     CrossRef
  • 3,415 View
  • 214 Download
  • 1 Crossref
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Gastrointestinal cancer
Trends in Chemotherapy Patterns and Survival of Patients with Advanced Gastric Cancer over a 16-Year Period: Impact of Anti-HER2–Targeted Agent in the Real-World Setting
Dong-Hoe Koo, Min-Hee Ryu, Mi-Yeon Lee, Heejung Chae, Eo Jin Kim, Mee-Sun Moon, Yoon-Koo Kang
Cancer Res Treat. 2021;53(2):436-444.   Published online October 6, 2020
DOI: https://doi.org/10.4143/crt.2020.725
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the survivals of patients with metastatic or recurrent gastric cancer (MRGC) over a period of 16 years and to investigate the recent changes in chemotherapy patterns.
Materials and Methods
A total of 5,384 patients who received chemotherapy for MRGC between 2000 and 2015 were analyzed. The analysis focused on a comparison of the first-line chemotherapy between four periods: 2000–2003 (period 1), 2004–2007 (period 2), 2008–2011 (period 3), and 2012–2015 (period 4).
Results
There were 880 patients (16%) in period 1, 1,573 (29%) in period 2, 1,435 (27%) in period 3, and 1,496 (28%) in period 4. Cytotoxic doublet-based therapy was the most commonly used (78%) first-line chemotherapy, and the combination of trastuzumab and doublet chemotherapy was provided to 288 patients. The OS rates at 12 and 24 months were steadily improved as follows: 39.2% and 14.6% in period 1, 43.5% and 17.6% in period 2, 50.3% and 20.6% in period 3, and 51.7% and 24.1% in period 4, respectively (p < 0.001). Among the patients who received the doublet-based chemotherapy, the median OS of those who received trastuzumab was 18.0 months (95% CI, 15.5–20.6), while that of those who received other doublet therapies was 11.2 months (95% CI, 10.8–11.6).
Conclusion
The OS was improved over time with advancements in chemotherapy, particularly the introduction of the anti-HER2–targeted agent, which contributed to the increase in the number of long-term survivors and established the superiority of OS for the treatment of MRGC.

Citations

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  • Factors associated with the efficacy of first-line nivolumab plus chemotherapy in advanced gastric cancer patients with deficient mismatch repair
    Young-Gyu Park, Hyung-Don Kim, Jaewon Hyung, Young Soo Park, Min-Hee Ryu
    Gastric Cancer.2024; 27(4): 840.     CrossRef
  • Varlitinib and Paclitaxel for EGFR/HER2 Co-expressing Advanced Gastric Cancer: A Multicenter Phase Ib/II Study (K-MASTER-13)
    Dong-Hoe Koo, Minkyu Jung, Yeul Hong Kim, Hei-Cheul Jeung, Dae Young Zang, Woo Kyun Bae, Hyunki Kim, Hyo Song Kim, Choong-kun Lee, Woo Sun Kwon, Hyun Cheol Chung, Sun Young Rha
    Cancer Research and Treatment.2024; 56(4): 1136.     CrossRef
  • Breakthroughs in the Systemic Treatment of HER2-Positive Advanced/Metastatic Gastric Cancer: From Singlet Chemotherapy to Triple Combination
    Sun Young Rha, Hyun Cheol Chung
    Journal of Gastric Cancer.2023;[Epub]     CrossRef
  • Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab
    Kyunghye Bang, Jaekyung Cheon, Young Soo Park, Hyung-Don Kim, Min-Hee Ryu, Yangsoon Park, Meesun Moon, Hyungeun Lee, Yoon-Koo Kang
    Gastric Cancer.2022; 25(4): 794.     CrossRef
  • Clinicopathological features and CT findings of papillary gastric adenocarcinoma
    Mengying Xu, Song Liu, Xiangmei Qiao, Lin Li, Changfeng Ji, Zhengyang Zhou
    Abdominal Radiology.2022; 47(11): 3698.     CrossRef
  • New prognostic model for patients with advanced gastric cancer: Fluoropyrimidine/platinum doublet for first-line chemotherapy
    Dong-Hoe Koo, Min-Hee Ryu, Mi-Yeon Lee, Mee-Sun Moon, Yoon-Koo Kang
    World Journal of Gastroenterology.2021; 27(48): 8357.     CrossRef
  • 6,336 View
  • 162 Download
  • 6 Crossref
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Ramosetron versus Palonosetron in Combination with Aprepitant and Dexamethasone for the Control of Highly-Emetogenic Chemotherapy-Induced Nausea and Vomiting
Jin Hyoung Kang, Jung Hye Kwon, Yun-Gyoo Lee, Keon Uk Park, Ho Jung An, Joohyuk Sohn, Young Mi Seol, Hyunwoo Lee, Hwan-Jung Yun, Jin Seok Ahn, Ji Hyun Yang, Hunho Song, Dong-Hoe Koo, Jin Young Kim, Gun Min Kim, Hwa Jung Kim
Cancer Res Treat. 2020;52(3):907-916.   Published online March 18, 2020
DOI: https://doi.org/10.4143/crt.2019.713
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)–induced nausea and vomiting.
Materials and Methods
Patients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by gender, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6.
Results
A total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], −7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, −2.3%; 95% CI, −13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, −7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups.
Conclusion
In all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

Citations

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    Büşra Burcu, Nadir Adnan Hacım, Ozan Caliskan, Serdar Demirgan, Talar Vartanoglu Aktokmakyan, Serhat Meric, Tomris Duymaz, Onder Karabay, Ali Solmaz
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    Critical Reviews in Oncology/Hematology.2020; 152: 103012.     CrossRef
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Practice Patterns Regarding Multidisciplinary Cancer Management and Suggestions for Further Refinement: Results from a National Survey in Korea
Yun-Gyoo Lee, Sukjoong Oh, Heejin Kimm, Dong-Hoe Koo, Do Yeun Kim, Bong-Seog Kim, Seung-Sei Lee
Cancer Res Treat. 2017;49(4):1164-1169.   Published online February 22, 2017
DOI: https://doi.org/10.4143/crt.2016.517
AbstractAbstract PDFPubReaderePub
Purpose
This study was conducted to explore the process and operation of a cancer multidisciplinary team (MDT) after the reimbursement decision in Korea, and to identify ways to overcome the major barriers to effective and sustainable MDTs.
Materials and Methods
Approximately 1,000 cancer specialists, including medical oncologists, surgical oncologists, radiation oncologists, pathologists, and radiologists in general hospitals in Koreawere invited to complete the survey. The questionnaire covered the following topics: organizational structure of MDTs, candidates for consulting, the clinical decision-making initiative, and responsibility for dealing with legal disputes.
Results
We collected a total of 179 responses (18%) from physicians at institutions where an MDT approachwas active. A surgical oncologist (91%), internist (90%),radiologist (89%),radiation oncologist (86%), pathologist (71%), and trainees (20%) regularly participated in MDT operations. Approximately 55% of respondents stated that MDTs met regularly. In cases of a split opinion, the physician in charge (69%) or chairperson (17%) made the final decision, and most (86%) stated they followed the final decision. About 15% and 32% of respondents were “very satisfied” and “satisfied,” respectively, with the current MDT’s operations. Among 38 institutional representatives, 34% responded that the MDT operation became more active and 18% stated an MDT was newly implemented after the reimbursement decision.
Conclusion
The reimbursement decision invigorated MDT operations in almost half of eligible hospitals. Dissatisfaction regarding current MDTs was over 50%, and the high discordance rates regarding risk sharing suggest that it is necessary to revise the current system of MDTs.

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Special Article
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 Res Treat. 2016;48(4):1155-1166.   Published online June 24, 2016
DOI: https://doi.org/10.4143/crt.2016.187
AbstractAbstract PDFPubReaderePub
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries.

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