Cancer Research and Treatment

Original Articles

Predictive Value of the nProfiler 1 Assay for the Efficacy of Adjuvant S-1-Based Doublet Chemotherapy in Stage III Gastric Cancer: A Post-Hoc Analysis of a Randomized Phase III Trial: Dong Ki Lee, Choong-kun Lee, Hyo Song Kim, Sun Jin Sym, Dae Young Zang, Ki Hyang Kim, Joo Han Lim, Hae Su Kim, Kyung Hee Lee, Heon Yung Gee, Sun Young Rha, Hyunki Kim, Minkyu Jung; Received July 25, 2024 Accepted November 9, 2024 Published online November 12, 2024; DOI: https://doi.org/10.4143/crt.2024.705 [Accepted]

Abstract PDF: Purpose
The nProfiler 1 Stomach Cancer Assay (nProfiler1), designed to predict responses to fluorouracil-based adjuvant chemotherapy, measures the expression of four gastric cancer target genes (GZMB, WARS, SFRP4, and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial.
Materials and Methods
The nProfiler1 assay stratifies patients into three groups (low-risk, intermediate-risk, and high-risk) using the prognostic single-patient classifier and two groups (chemotherapy-benefit and no-benefit) using the predictive single-patient classifier. The nProfiler1 assay was applied to formalin-fixed paraffin-embedded slides obtained from the POST trial. Disease-free survival (DFS) and overall survival (OS), including 5-year survival rates, were calculated for the enrolled patients.
Results
Of the 153 patients in the POST trial, 118 were included in the post-hoc analysis. With a median follow-up of 57.9 months, no significant difference in DFS or OS was observed between the SP and DS groups. The prognostic single-patient classifier predicted the OS in the SP group (p=0.0425) but not in the DS group (p=0.5940). The chemotherapy-benefit group exhibited numerically longer DFS than the no-benefit group in the SP and DS groups.
Conclusion
The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.

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Prognostic Factors for Risk Stratification of Patients with Recurrent or Metastatic Pancreatic Adenocarcinoma Who Were Treated with Gemcitabine-Based Chemotherapy: Inkeun Park, Seung Joon Choi, Young Saing Kim, Hee Kyung Ahn, Junshik Hong, Sun Jin Sym, Jinny Park, Eun Kyung Cho, Jae Hoon Lee, Yong Ju Shin, Dong Bok Shin; Cancer Res Treat. 2016;48(4):1264-1273. Published online March 23, 2016; DOI: https://doi.org/10.4143/crt.2015.250

Purpose
The aim of this study was to verify prognostic factors including sarcopenia in patients with recurrent or metastatic pancreatic cancer receiving gemcitabine-based chemotherapy. Materials and Methods Medical records and computed tomography scan of consecutive patients treated with palliative gemcitabine-based chemotherapy from 2008 to 2014 were reviewed. The lumbar skeletal muscle index at third lumbar spine level was computed, and together with clinicolaboratory factors, univariate and multivariable analyses for overall survival (OS) were performed.
Results
A total of 88 patients were found. Median age was 65 years, and male patients were predominant (67.0%). Most patients had initially metastatic disease (72.7%), and gemcitabine monotherapy was administered in 29 patients (33.0%) while gemcitabine plus erlotinib was administered in 59 patients (67.0%). Seventy-six patients (86.3%) had sarcopenia. With a median follow-up period of 44.3 months (range, 0.6 to 44.3 months), median OS was 5.35 months (95% confidence interval [CI], 4.11 to 6.59). In univariate and multivariable analysis, high carcinoembryonic antigen level (hazard ratio [HR], 4.18; 95% CI, 1.95 to 8.97; p < 0.001), initially metastatic disease (HR, 3.37; 95% CI, 1.55 to 7.32; p=0.002), sarcopenia (HR, 2.97; 95% CI, 1.20 to 7.36; p=0.019), neutrophilia (HR, 2.94; 95% CI, 1.27 to 6.79; p=0.012), and high lactate dehydrogenase level (HR, 1.96; 95% CI, 1.07 to 3.58; p=0.029) were identified as independent prognostic factors for OS. Conclusion Five independent prognostic factors in patients with recurrent or metastatic pancreatic cancer who received gemcitabine-based chemotherapy were identified. These findings may be helpful in prediction of prognosis in clinical practice and can be used as a stratification factor for clinical trials.

Citations

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Johanna Mandl, Sebastian Baumer, Bernadette Holtzem, Rainer Theurer, Niels Zorger, Oliver Pech
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A Korean Nationwide Survey for Breakthrough Cancer Pain in an Inpatient Setting: Sun Kyung Baek, Do Yeun Kim, Seok Yun Kang, Sun Jin Sym, Young Sung Kim, June Young Lee; Cancer Res Treat. 2016;48(2):768-774. Published online September 15, 2015; DOI: https://doi.org/10.4143/crt.2015.087

Abstract PDF PubReader ePub

Purpose
We evaluated the prevalence and characteristics of breakthrough cancer pain (BTcP) in Korean patients admitted with cancer pain.
Materials and Methods
In-hospital patients with cancer pain completed a questionnaire concerning severity of background cancer pain (BCP), prevalence and treatment for BTcP, sleep disorders, and satisfaction with cancer pain treatment. Medical records showing medications for BCP and BTcP were also evaluated.
Results
Total 609 patients with controlled BCP enrolled. Mean age of the patients was 59.5 years old, and 59% were male. Of all patients, 177 (29%) complained of BTcP. No clinical characteristic predicted BTcP. Of the 177 patients with BTcP, 56% did not receive treatment for BTcP. Patients with BTcP showed significant association with a sleep disorder and dissatisfaction with pain control, compared to those without BTcP (p < 0.0001 and p=0.0498, respectively). Oxycodone-immediate release was the most commonly used short-acting analgesic, followed by intravenous morphine.
Conclusion
The prevalence of BTcP was 29% in patients admitted with controlled BCP. Although the patients had well-controlled BCP, BTcP showed association with a lower quality of life in patients with cancer. More medical attention is needed for detection and management of BTcP.

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Breakthrough pain among cancer patients at oncology units in Northern Ethiopia; a multi-center study
Yohanes Tekie, Yonas Addisu Nigatu, Wudie Mekonnen, Yophtahe Woldegerima Berhe
Frontiers in Oncology.2024;[Epub] CrossRef
Predicting tolerability of high-dose fentanyl buccal tablets in cancer patients
Mi-Young Kwon, Mi-Yeon Lee, Yun Jae Han, Sung Hyun Lee, Eo Jin Kim, Songyi Park, Yun‑Gyoo Lee, Dong-Hoe Koo, Muhammad Hanif
PLOS ONE.2023; 18(1): e0280212. CrossRef
Knowledge and practice of the management of breakthrough cancer pain among general practitioners providing palliative care in Shanghai, China: a cross-sectional survey
Ying Yu, Panpan Zhang, Danxia Chen, Sun Fang Jiang
BMJ Open.2023; 13(9): e073670. CrossRef
Effect of a theory-driven educational intervention on the level of knowledge, attitudes, and assessment practices regarding breakthrough cancer pain (BTCP) management among medical nurses in Hong Kong
Carman Y.L. Kwok, Dorothy N.S. Chan, Winnie K.W. So
European Journal of Oncology Nursing.2021; 52: 101945. CrossRef
Observational study of efficacy, safety, and tolerability of fentanyl in Korean cancer patients (OASIS)
Youn Seon Choi, Su-Jin Koh, Woo Kyun Bae, Se Hyung Kim, Seong Hoon Shin, So Yeon Oh, Sang Byung Bae, Yaewon Yang, Eun-Kee Song, Yoon Young Cho, Pyung Bok Lee, Ho-Suk Oh, Sang Won Park, Jin Seok Ahn
Medicine: Case Reports and Study Protocols.2021; 2(3): e0088. CrossRef
Significance of descriptive symptoms and signs and clinical parameters as predictors of neuropathic cancer pain
Sun Kyung Baek, Sang Won Shin, Su-Jin Koh, Jung Han Kim, Hyo Jung Kim, Byoung Yong Shim, Seok Yun Kang, Sang Byung Bae, Hwan Jung Yun, Sun Jin Sym, Hye Sook Han, Ha Yeong Gil, Ahmed Negida
PLOS ONE.2021; 16(8): e0252781. CrossRef
Interference with daily functioning by breakthrough pain in patients with cancer
Jung Hun Kang, Su-Jin Koh, So Yeon Oh, Rock Bum Kim, Seong Hoon Shin, Yun-Gyoo Lee, Bong-Seog Kim, Hun Mo Ryoo, So Young Yoon, Joung Soon Jang, Ho-Suk Oh, Young Jin Choi, Moon Hee Lee, Kyung-Hee Lee
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Endogenous Opiates and Behavior: 2016
Richard J. Bodnar
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Initial titration with 200 μg fentanyl buccal tablets: a retrospective safety analysis in Korean cancer patients
Mi-Young Kwon, Ha-Na Cho, Dong-Hoe Koo, Yun-Gyoo Lee, Sukjoong Oh, Seung-Sei Lee
The Korean Journal of Internal Medicine.2018; 33(3): 577. CrossRef

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Randomized Phase II Study of Pemetrexed Versus Gefitinib in Previously Treated Patients with Advanced Non-small Cell Lung Cancer: Young Saing Kim, Eun Kyung Cho, Hyun Sun Woo, Junshik Hong, Hee Kyung Ahn, Inkeun Park, Sun Jin Sym, Sun Young Kyung, Shin Myung Kang, Jeong-Woong Park, Sung Hwan Jeong, Jinny Park, Jae Hoon Lee, Dong Bok Shin; Cancer Res Treat. 2016;48(1):80-87. Published online March 2, 2015; DOI: https://doi.org/10.4143/crt.2014.307

Abstract PDF PubReader ePub

Purpose
This study aimed to evaluate the efficacy and safety of pemetrexed versus gefitinib in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. Materials and Methods Patients with advanced (stage IIIB or IV) or recurrent NSCLC were randomly assigned to receive either 500 mg/m² of pemetrexed intravenously every 3 weeks or gefitinib 250 mg/day orally. The primary end point was progression-free survival (PFS) at 6 months.
Results
A total of 95 patients were enrolled (47 for pemetrexed and 48 for gefitinib). Most patients were male (72%) and current/ex-smokers (69%), and 80% had non-squamous cell carcinoma. The epidermal growth factor receptor (EGFR) mutation status was determined in 38 patients (40%); one patient per each arm was positive for EGFRmutation. The 6-month PFS rates were 22% and 15% for pemetrexed and gefitinib, respectively (p=0.35). Both arms showed an identical median PFS of 2.0 months and a median overall survival (OS) of 8.5 months. In EGFR wild-type patients, higher response rate (RR) and longer PFS as well as OS were achieved via pemetrexed compared with gefitinib, although there were no significant differences (RR: 39% vs. 9%, p=0.07; median PFS: 6.6 months vs. 3.1 months, p=0.45; median OS: 29.6 months vs. 12.9 months, p=0.62). Toxicities were mild in both treatment arms. Frequently reported toxicities were anemia and fatigue for pemetrexed, and skin rash and anorexia for gefitinib. Conclusion Both pemetrexed and gefitinib had similar efficacy with good tolerability as second-line treatment in unselected patients with advanced NSCLC. However, pemetrexed is considered more effective than gefitinib for EGFR wild-type patients.

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Himani Aggarwal, Kerigo Ndirangu, Katherine B Winfree, Catherine Elizabeth Muehlenbein, Emily Zhu, Vanita Tongbram, Howard Thom
Journal of Comparative Effectiveness Research.2023;[Epub] CrossRef
Toxicity profile of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung cancer: A systematic review and network meta-analysis
Yi Zhao, Bo Cheng, Zisheng Chen, Jianfu Li, Hengrui Liang, Ying Chen, Feng Zhu, Caichen Li, Ke Xu, Shan Xiong, Weixiang Lu, Zhuxing Chen, Ran Zhong, Shen Zhao, Zhanhong Xie, Jun Liu, Wenhua Liang, Jianxing He
Critical Reviews in Oncology/Hematology.2021; 160: 103305. CrossRef
Efficacy and Safety of Pemetrexed and Gefitinib in the Treatment of Non-Small-Cell Lung Cancer: A Meta-Analysis
Zhihao Zhang, Xiyong Wang, Huaiqing Xiao, Dongqiang Wu, Dongliang Zhang, Qun Yu, Linna Yuan, Tao Huang
Computational and Mathematical Methods in Medicine.2021; 2021: 1. CrossRef
A meta-analysis of the safety and effectiveness of pemetrexed compared with gefitinib for pre-treated advanced or metastatic NSCLC
Xiaoxin Lu, Shengshu Li, Weizong Chen, Dongyang Zheng, Yuzhu Li, Fang Li
Medicine.2020; 99(29): e21170. CrossRef
Pemetrexed versus Gefitinib as Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Meta-analysis Based on Randomized Controlled Trials
Huiyu Wang, Zunjing Zhang, Feng Liu, Miaoying Zhou, Handi Lv
Pteridines.2019; 30(1): 171. CrossRef
Gefitinib for advanced non-small cell lung cancer
Esther HA Sim, Ian A Yang, Richard Wood-Baker, Rayleen V Bowman, Kwun M Fong
Cochrane Database of Systematic Reviews.2018;[Epub] CrossRef
Pneumonitis in advanced non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitor: Meta-analysis of 153 cohorts with 15,713 patients
Chong Hyun Suh, Hye Sun Park, Kyung Won Kim, Junhee Pyo, Hiroto Hatabu, Mizuki Nishino
Lung Cancer.2018; 123: 60. CrossRef
Second-Line Treatment of NSCLC—The Pan-ErbB Inhibitor Afatinib in Times of Shifting Paradigms
Jens Köhler
Frontiers in Medicine.2017;[Epub] CrossRef

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Case Reports

Oxaliplatin-Induced Immune-Mediated Thrombocytopenia: A Case Report: Hyun Sun Woo, Kyoung Hwa Lee, Phill Hoon Yoon, Su Ji Kim, Inkeun Park, Young Saing Kim, Hee Kyung Ahn, Junshik Hong, Dong Bok Shin, Sun Jin Sym; Cancer Res Treat. 2015;47(4):949-953. Published online October 28, 2014; DOI: https://doi.org/10.4143/crt.2014.052

Abstract PDF PubReader ePub

Oxaliplatin is a third-generation platinum derivative used for metastatic or advanced colorectal cancer treatment. Although myelosuppression is the most common cause of oxaliplatin-induced thrombocytopenia, rare cases of oxaliplatin-induced immunemediated thrombocytopenia are reported. We report a case of a 57-year-old woman with colon cancer who developed gum bleeding and petechiae after oxaliplatin infusion. Laboratory tests revealed grade 4 thrombocytopenia and grade 4 neutropenia. She recovered from the thrombocytopenia and accompanying neutropenia within 4 days with no recurrence following discontinuation of oxaliplatin. Physicians need to be aware of the risk of severe acute thrombocytopenia following oxaliplatin administration.

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Ju Li, Wanqing Wang, Kaipeng Jiang, Jiuwei Cui, Chang Wang, Tingting Liang, Yizhuo Wang, Shuhan Liu, Wenshuo Zhou
Journal of Gastrointestinal Cancer.2024; 55(3): 1144. CrossRef
Oxaliplatin Antibody-Related Thrombocytopenia: A Case Report
Khin Pyai, David I LeRoy, Joseph Attallah, Hosam Hakim, Zyad Kafri
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Recurrent and Metastatic Trichilemmal Carcinoma of the Skin Over the Thigh: A Case Report: Hyon Seung Yi, Sun Jin Sym, Jinny Park, Eun Kyung Cho, Seung-Yeon Ha, Dong Bok Shin, Jae Hoon Lee; Cancer Res Treat. 2010;42(3):176-179. Published online September 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.3.176

Abstract PDF PubReader ePub

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

Citations

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Original Article

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

Abstract PDF PubReader ePub

Purpose

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

Materials and Methods

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

Results

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

Conclusion

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

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