Cancer Medicine最新文献

{"title":"The Association Between Serum Gamma-Glutamyl Transferase and Gastrointestinal Cancer Risk: A Systematic Review and Meta-Analysis.","authors":"Alireza Ramandi, Jacob George, Amir Hossein Behnoush, Alireza Delavari, Zahra Mohammadi, Hossein Poustchi, Reza Malekzadeh","doi":"10.1002/cam4.70581","DOIUrl":"https://doi.org/10.1002/cam4.70581","url":null,"abstract":"<p><strong>Background: </strong>Gamma-glutamyl transferase (GGT) has been shown to have associations with several diseases including cancers. Previous studies have investigated the effect of GGT levels on the gastrointestinal (GI) cancer incidence. We aim to systematically investigate these studies to provide better insights into the interrelationship between GGT and GI cancers.</p><p><strong>Methods: </strong>Online databases were searched to find relevant studies investigating different GGT levels' effects on the incidence of GI cancers including colorectal, esophageal, liver, pancreas, gastric, and biliary duct cancers. Random-effect meta-analysis was conducted to pool the hazard ratios (HRs) of GGT quartiles (Qs) effect on cancer incidence.</p><p><strong>Results: </strong>A total of 26 studies were included in the final review, 12 of which underwent meta-analysis that investigated 11 million patients. Based on the meta-analysis, Q4 patients had a 69% higher hazard of GI cancer incidence (HR 1.69, 95% CI 1.41-2.02, p-value < 0.001). The hazard ratio significance was also similar for Q3 (HR 1.22, 95% CI 1.15-1.30, p-value < 0.001) and Q2 (HR 1.10, 95% CI 1.05-1.16, p-value =0.002) of GGT. Colorectal and liver cancers showed a higher hazard ratio among Q2, Q3, and Q4 of GGT compared to Q1. In pancreas and bile duct cancers, only Q4 of GGT had significantly higher HR. Q3 and Q4 of GGT levels had statistically significant associations with gastric cancer incidence.</p><p><strong>Conclusion: </strong>Higher GGT levels correlate with higher rates of GI cancer incidence, especially in colorectal and hepatic cancers. Future studies should investigate this biomarker's potential role in risk assessment for digestive cancers.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":"e70581"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"ARHGAP42 Promotes Cell Migration and Invasion Involving PI3K/Akt Signaling Pathway in Nasopharyngeal Carcinoma\".","authors":"","doi":"10.1002/cam4.70559","DOIUrl":"10.1002/cam4.70559","url":null,"abstract":"","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 1","pages":"e70559"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Learning and Multidisciplinary Imaging in Pediatric Surgical Oncology: A Scoping Review.","authors":"M A D Buser, J K van der Rest, M H W A Wijnen, R R de Krijger, A F W van der Steeg, M M van den Heuvel-Eibrink, M Reismann, S Veldhoen, L Pio, M Markel","doi":"10.1002/cam4.70574","DOIUrl":"10.1002/cam4.70574","url":null,"abstract":"<p><strong>Background: </strong>Medical images play an important role in diagnosis and treatment of pediatric solid tumors. The field of radiology, pathology, and other image-based diagnostics are getting increasingly important and advanced. This indicates a need for advanced image processing technology such as Deep Learning (DL).</p><p><strong>Aim: </strong>Our review focused on the use of DL in multidisciplinary imaging in pediatric surgical oncology.</p><p><strong>Methods: </strong>A search was conducted within three databases (Pubmed, Embase, and Scopus), and 2056 articles were identified. Three separate screenings were performed for each identified subfield.</p><p><strong>Results: </strong>In total, we identified 36 articles, divided between radiology (n = 22), pathology (n = 9), and other image-based diagnostics (n = 5). Four types of tasks were identified in our review: classification, prediction, segmentation, and synthesis. General statements about the studies'' performance could not be made due to the inhomogeneity of the included studies. To implement DL in pediatric clinical practice, both technical validation and clinical validation are of uttermost importance.</p><p><strong>Conclusion: </strong>In conclusion, our review provided an overview of all DL research in the field of pediatric surgical oncology. The more advanced status of DL in adults should be used as guide to move the field of DL in pediatric oncology further, to keep improving the outcomes of children with cancer.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":"e70574"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Financial Toxicity on the Health-Related Quality of Life and Financial Well-Being of Cancer Patients and Survivors: A Comparative Study of the United Kingdom and United States.","authors":"Tran Thu Ngan, Emily Tonorezos, Michael Donnelly, Ciaran O'Neill","doi":"10.1002/cam4.70606","DOIUrl":"10.1002/cam4.70606","url":null,"abstract":"<p><strong>Background: </strong>This study investigated and compared the impact of financial toxicity (FT) on the health-related quality of life (HRQoL) and financial well-being of cancer patients and survivors in the United Kingdom (UK) and United States (US).</p><p><strong>Methods: </strong>UK & US participants (n = 600) completed an online questionnaire that consisted of a validated FT instrument (COmprehensive Score for financial Toxicity-COST), a standardised HRQoL instrument (EQ-5D-5L) and questions related to their financial well-being. Tobit regression models and descriptive statistics plus χ² tests were used to analyse the association between FT and (i) HRQoL whilst controlling for sociodemographic characteristics; and (ii) financial well-being.</p><p><strong>Results: </strong>In the UK, health utilities of participants with no assessed experience of FT, mild FT, and moderate/severe FT were 0.81, 0.66, and 0.41, respectively, compared to 0.88, 0.71, and 0.53 in the US. Among those with moderate/severe FT, US participants had significantly higher health utilities compared to their peers in the UK (Mann Whitney test, p = 0.0369). In a pooled analysis of UK and US and after controlling for sociodemographic and clinical characteristics, mild and moderate/severe FT was negatively associated with health utilities (β coff = -0.13, 95% CI: -0.18, -0.08 and β coff = -0.28, 95% CI: -0.34, -0.21, respectively). Over half (54%) of US participants with FT were in debt with median (IQR) debt at I$11,500 (23,000), compared to 32% in the UK with median (IQR) debt at I$ 7200 (12,960). US participants with FT were 2.48 times more likely to be in debt than UK participants with FT (OR = 2.48, 95% CI: 1.46-4.21).</p><p><strong>Conclusions: </strong>FT is associated with poorer financial well-being and HRQoL among cancer patients/survivors in the US and UK. The impact of FT on financial well-being is larger in the US while the impact on HRQoL is worse in the UK. Further studies using prospective data are required to investigate the nature and extent of these relationships.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":"e70606"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drivers of Palliative Care and Hospice Use Among Patients With Advanced Lung Cancer.","authors":"Megan C Edmonds, Melissa Mazor, Mayuri Jain, Lihua Li, Marsha Augustin, José Morillo, Olivia S Allen, Amina Avril, Juan P Wisnivesky, Cardinale B Smith","doi":"10.1002/cam4.70518","DOIUrl":"https://doi.org/10.1002/cam4.70518","url":null,"abstract":"<p><strong>Purpose: </strong>Despite rigorous evidence of improved quality of life and longer survival, disparities in the utilization of palliative and hospice care persist for racial and ethnic minority patients with cancer. This study evaluated the impact of psychosocial factors on utilization of these services.</p><p><strong>Methods: </strong>Patients with advanced lung cancer were recruited at a large academic urban hospital. Patients were surveyed about their knowledge of palliative care and hospice and their beliefs regarding medical mistrust, lung cancer care, palliative care and hospice. We used univariate and multivariable logistic regression analyses to examine the association between mistrust, knowledge and beliefs among the entire cohort and minority (Black and Hispanic) and non-minority patients on utilization of palliative care consultation and hospice care use.</p><p><strong>Results: </strong>Ninety-nine of the enrolled participants had a mean age of 64 years. Minority patients were more likely to receive a palliative care referral (p < 0.001) and attend a consult (p = 0.003). Similarly, they were more likely to receive a hospice referral (p = 0.04), however there was no difference in hospice care use based on minority status (p = 0.102). In our adjusted model, older patients and those reporting negative lung cancer beliefs were more likely to receive hospice care (OR: 1.06, 95% CI: 1.004-1.138; OR: 1.04, 95% CI: 1.002-1.093, respectively).</p><p><strong>Conclusion: </strong>Minority patients with advanced lung cancer were more likely to receive a palliative care referral and specialty level consultation when compared to non-minority patients. Our work highlights the importance of proactive referral processes in facilitating access to palliative and hospice services, particularly among younger patients.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 2","pages":"e70518"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Multi-Kinase Inhibitor GZD824 (Olverembatinib) Shows Pre-Clinical Efficacy in Endometrial Cancer.","authors":"Dongli Liu, Dylan Glubb, Tracy O'Mara, Caroline E Ford","doi":"10.1002/cam4.70531","DOIUrl":"10.1002/cam4.70531","url":null,"abstract":"<p><strong>Objective: </strong>Endometrial cancer is one of the few cancers for which mortality is still increasing. A lack of treatment options remains a major challenge, particularly for some subtypes of the disease. GZD824, also known as olverembatinib, is a multi-kinase inhibitor previously investigated in clinical trials for chronic myeloid leukaemia and Ph+ acute lymphoblastic leukaemia as a BCR-ABL inhibitor. This study aimed to investigate the pre-clinical efficacy of GZD824 for the treatment of EC.</p><p><strong>Methods: </strong>Here, we undertook pre-clinical evaluation of GZD824 in seven endometrial cancer cell lines (HEC-1-A, HEC-1-B, MFE296, RL95-2, Ishikawa, KLE and ARK-1), one normal immortalised endometrium derived cell line (E6E7hTERT) and primary mesothelial and fibroblast cells isolated from normal omentum samples.</p><p><strong>Results: </strong>GZD824 inhibited the proliferation of all endometrial cancer cell lines, which were significantly more sensitive to GZD824 compared to normal cells (p = 0.030). GZD824 significantly inhibited migration in Ishikawa (endometrioid) and ARK1 (serous) endometrial cancer cell lines and significantly inhibited invasion in the ARK1 cells. Whole transcriptome regulation following two doses (0.1 and 1 μM) of GZD824 in Ishikawa and ARK1 cells was investigated via RNA-seq, and key components of enriched pathways were investigated at the translational level. Key pathways altered included ROR1/Wnt, GCN2-ATF4, epithelial to mesenchymal transition (EMT) and PI3K-AKT.</p><p><strong>Conclusion: </strong>Together, these studies support further investigation of GZD824 as a potential therapeutic agent in endometrial cancer, potentially in combination with immune checkpoint inhibitors.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 1","pages":"e70531"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Asthma Affect the Risk of Developing Breast Cancer?","authors":"Karin B Michels, Orianne Dumas, Raphaelle Varraso, Carlos A Camargo","doi":"10.1002/cam4.70539","DOIUrl":"10.1002/cam4.70539","url":null,"abstract":"<p><strong>Background: </strong>The role of the immune system in cancer defense is likely underappreciated. While there has been longstanding interest in the role of atopic diseases in cancer, only a few studies have tested this hypothesis.</p><p><strong>Methods: </strong>We analyzed data from 202,055 women participating in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II) to explore whether asthma is associated with breast cancer. We used Cox proportional hazards models to link physician-diagnosed asthma with subsequent incidence of breast cancer.</p><p><strong>Results: </strong>Across the two cohorts, we identified 18,403 cases of physician-diagnosed asthma. During 4,393,760 person-years of follow-up, 11,096 incident cases of breast cancer were diagnosed. In NHS, women with asthma had a covariate-adjusted hazard ratio of 0.92 (95% CI: 0.86-0.99) to develop breast cancer compared to women without asthma; the respective HR in NHS II was 0.93 (0.84-1.03), and 0.92 (0.87-0.98) in the pooled analysis. Among never-smokers, the HR for breast cancer was 0.91 (0.81-1.02) in NHS, 0.81 (0.70-0.93) in NHS II, and 0.86 (0.77-0.97) combined. In two large prospective cohorts of women, participants with asthma had a somewhat lower risk of breast cancer. An active immune system may provide protection from breast cancer.</p><p><strong>Conclusions: </strong>In these longitudinal studies, women with asthma had a somewhat lower risk of breast cancer. This association was most pronounced among never smokers. An active immune system may provide protection from breast cancer.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 1","pages":"e70539"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11686484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and Safety of Treatments for Early-Stage Merkel Cell Carcinoma: A Systematic Review and Meta-Analysis of Randomized and Non-Randomized Studies.","authors":"Yves Paul Vincent Mbous, Rowida Mohamed, Usha Sambamoorthi, Murtuza Bharmal, Khalid M Kamal, Traci LeMasters, Joanna Kolodney, George A Kelley","doi":"10.1002/cam4.70553","DOIUrl":"10.1002/cam4.70553","url":null,"abstract":"<p><strong>Objective: </strong>The lack of consensus on the benefits and harms of standard therapies, including surgery (SRx), radiotherapy (RTx), chemotherapy (CTx), and their combinations among early-stage MCC, prompted this study.</p><p><strong>Methods: </strong>A systematic review and meta-analysis of randomized and non-randomized studies published between January 01, 1972, and January 31, 2023, and having overall survival (OS), local recurrence (LR), regional recurrence (RR), disease-specific survival (DSS), and/or disease-free survival (DFS) as outcomes was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (NCBI), Scopus (ELSEVIER), and Web of Science (CLAVIRATE) databases. Hazard ratios (HRs) and their variances were pooled using the inverse variance heterogeneity model.</p><p><strong>Results: </strong>Forty-nine studies representing 46,215 participants were included in the meta-analysis. A statistically significant improvement in OS was observed for groups administered adjuvant RTx (SRx + RTx) compared to SRx only (HR = 0.78, 95% CI, 0.62-0.99), albeit with statistically significant heterogeneity (Q = 532.30, p < 0.001) and a large amount of inconsistency (I² = 94%, 95% CI, 93.0-95.5). Both LR (HR = 1.52, 95% CI, 0.37-6.19) and RR (HR = 0.41, 95% CI, 0.09-1.78) were not statistically significant. In addition, DSS (HR = 0.58, 95% CI, 0.24-1.40) was not statistically significant but DFS was (HR = 0.35, 95% CI, 0.13-0.93). Subgroup analyses revealed that adjuvant radiotherapy was more effective in local than regional MCC. The E-value suggested that the RTx dose was a confounder of the observed effectiveness of adjuvant RTx; and also, the use of CTx following adjuvant RTx, did not impact the strength of evidence for OS.</p><p><strong>Conclusions: </strong>Although adjuvant RTx improves survival and recurrence outcomes among early-stage MCC, the safety and effectiveness of standard therapies in MCC remains poorly studied and, thus, affects the synthesis of evidence across important patient and clinical characteristics. Future research on the comparative effectiveness of different therapies is needed.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 1","pages":"e70553"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum 25-Hydroxyvitamin D Levels and Survival Outcomes in Advanced Biliary Tract Cancer: Results From the NIFTY Trial.","authors":"So Heun Lee, Jaekyung Cheon, Ilhwan Kim, Kyu-Pyo Kim, Baek-Yeol Ryoo, Jae Ho Jeong, Myoung Joo Kang, Byung Woog Kang, Hyewon Ryu, Ji Sung Lee, Changhoon Yoo","doi":"10.1002/cam4.70560","DOIUrl":"10.1002/cam4.70560","url":null,"abstract":"<p><strong>Background: </strong>Numerous studies have explored the role of vitamin D in various cancers; however, its impact on advanced biliary tract cancers (BTC) within a prospective cohort remains to be investigated. This preplanned subgroup analysis of the NIFTY trial evaluated the prognostic implications of serum vitamin D levels in patients with advanced BTC undergoing second-line chemotherapy.</p><p><strong>Methods: </strong>From the 174 patients in the NIFTY trial, a total of 173 patients (99.4%) were included in this analysis comparing a liposomal irinotecan plus 5-FU/leucovorin group (n = 87) and a 5-FU/leucovorin alone group (n = 86). Baseline serum 25-hydroxyvitamin D (25(OH)D) levels, an indicator of vitamin D status, were analyzed for their association with baseline characteristics and overall survival (OS) in patients undergoing second-line chemotherapy. Multivariable Cox proportional hazards regression and a restricted cubic spline function were used to assess the association with OS.</p><p><strong>Results: </strong>There were no significant associations between baseline characteristics and serum 25(OH)D levels. Baseline serum 25(OH)D levels were not associated with OS in either the multivariable Cox proportional hazard regression or restricted cubic spline analysis. In the subgroup analysis, however, higher serum 25(OH)D levels were significantly associated with poorer OS in female patients, while no significant association was observed in male patients, indicating a significant interaction by sex. Additionally, a marginally significant interaction was observed between body mass index and serum 25(OH)D levels for OS, with higher levels associated with better OS in patients who were underweight.</p><p><strong>Conclusions: </strong>Our preplanned subgroup analysis of the NIFTY trial indicates that the serum 25(OH)D levels did not have a significant effect on OS in the overall patient population with advanced BTC. However, higher serum 25(OH)D levels were associated with worse OS in female patients, underscoring the need for further investigation into the role of vitamin D in BTC.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 1","pages":"e70560"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I Trial of Upamostat Combined With Gemcitabine in Locally Unresectable or Metastatic Pancreatic Cancer: Safety and Preliminary Efficacy Assessment.","authors":"Xiuping Lai, Di Cheng, Huixin Xu, Jingshu Wang, Xiaozhi Lv, Herui Yao, Liuning Li, Junyan Wu, Suiwen Ye, Zhihua Li","doi":"10.1002/cam4.70550","DOIUrl":"10.1002/cam4.70550","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to determine the maximum tolerated dose (MTD) of the urokinase plasminogen activator (uPA) inhibitor upamostat (LH011) in combination with gemcitabine for locally advanced unresectable or metastatic pancreatic cancer.</p><p><strong>Method: </strong>Seventeen patients were enrolled and received escalating doses of oral LH011 (100, 200, 400, or 600 mg) daily alongside 1000 mg/m² of gemcitabine. Safety profiles, tumor response (including response rate and progression-free survival), pharmacokinetics, and changes in CA199 and D-dimer levels were assessed.</p><p><strong>Results: </strong>During the study period (Day0-Day49), no patients achieved partial response. Stable disease (SD) was observed in 12 patients (70.6%), while four patients (23.5%) experienced progressive disease (PD). One patient withdrew due to a serious adverse event (SAE) on D47. Pharmacokinetic analysis revealed a dose-related increase in LH011 and its metabolite WX-UK1 exposure from 100 to 400 mg but not in the 600 mg group. Hematological toxicity, mainly attributable to gemcitabine, was the predominant grade 3 or 4 adverse event, with additional occurrences of loss of appetite, rash, and interstitial lung disease. Sinus bradycardia possibly linked to LH011 rather than gemcitabine was noted. The MTD was not reached.</p><p><strong>Conclusion: </strong>Combining LH011 at doses ranging from 100 to 600 mg with gemcitabine every 21 days demonstrated manageable safety and tolerability. However, tumor response did not significantly differ among the dose groups, suggesting the need for further investigation.</p><p><strong>Trial registration: </strong>NCT05329597.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 1","pages":"e70550"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}