Cancer Chemotherapy and Pharmacology最新文献

{"title":"Safety and preliminary efficacy results of a new micellar formulation of docetaxel in patients with metastatic castration-resistant prostate cancer - SAKK 67/20 trial.","authors":"Ilaria Colombo, Pascale C S Rietveld, Stefanie Fischer, Stefania Merlo, Ursula Vogl, Richard Cathomas, Stijn L W Koolen, Daniela Zoelly, Katrin Gobat, Charlotte Micheloud, Katrin Eckhardt, Cristiana Sessa, Anastasios Stathis, Aurelius Omlin, Markus Joerger","doi":"10.1007/s00280-026-04933-6","DOIUrl":"10.1007/s00280-026-04933-6","url":null,"abstract":"<p><strong>Purpose: </strong>Docetaxel micellar (DM) is a novel polysorbate-free docetaxel formulation that does not require steroid premedication. The aim of this study was to define the safety, pharmacokinetics (PK) and preliminary activity of DM in patients with metastatic castration-resistant prostate cancer (mCRPC).</p><p><strong>Methods: </strong>DM was administered intravenously to chemotherapy-naïve patients with mCRPC every 3 weeks following a 3 + 3 design (75, 90, 100 mg/m²) until disease progression or unacceptable toxicity (maximum 10 cycles).</p><p><strong>Results: </strong>A total of 11 patients were recruited from June 2021 to April 2023. No dose limiting toxicities (DLT) were observed at 75 or 90 mg/m². Two out of 5 patients experienced DLT at 100 mg/m² (grade 4 neutropenia ≥ 7 days and grade 2 nausea/fatigue/diarrhoea requiring dose reduction at cycle 2, respectively). Most frequent all-grades TRAE included fatigue (91%), neutropenia (82%), alopecia (64%), diarrhoea (55%), peripheral edema (45%) and peripheral sensory neuropathy (45%). Infusion-related reactions or febrile neutropenia were not observed. Four out of 11 (36%) patients achieved a PSA50 response, 4/9 (44%) evaluable patients achieved a radiological response. DM exhibited linear PK with tri-phasic elimination (clearance 26.6 L/h, 20% inter-individual PK variability). While 3-weekly intravenous DM at 90 mg/m² was not associated with DLT, no formal dosing recommendation was made for premature closure of the 100 mg/m² cohort.</p><p><strong>Conclusions: </strong>Steroid-free 3-weekly DM at a dose of 90 mg/m2 was not associated with DLT. Preliminary activity of DM appeared consistent with historical outcomes reported for conventional docetaxel in patients with mCRPC (NCT04629781).</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148856974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intensification versus combination: revisiting the past and envisioning the future of LDHA inhibitors.","authors":"Weixi Yuan, Qiang Kang, Yin Zhao, Zhe Wang, Yujia He, Chengxiao Fu, Hongxiang Xiao, Xiaoyong Lei, Zhizhong Xie, Xiaoyan Yang, Bo Yang, Guotao Tang, Xiangping Deng","doi":"10.1007/s00280-026-04918-5","DOIUrl":"https://doi.org/10.1007/s00280-026-04918-5","url":null,"abstract":"<p><p>As a key enzyme in pyruvate metabolism, lactate dehydrogenase A (LDHA) has been extensively studied for its role in cellular energy regulation and disease pathology. Given its central role in the Warburg effect (cancer cells have a higher intensity of glycolysis even under oxygen-rich conditions) cytoplasmic LDHA emerges as a strategic therapeutic target for tumor suppression through glycolytic pathway inhibition. Despite extensive research, the development of effective LDHA inhibitors has seen limited success, highlighting the urgent need to reassess its molecular properties and refine drug design strategies. In this review, we systematically analyze LDHA's structural biology, critically evaluate the strengths and shortcomings of current inhibitors, and propose novel conceptual frameworks for inhibitor development based on recent insights into LDHA-mediated glycolysis reprogramming. By integrating recent insights into LDHA-mediated glycolysis reprogramming, this review lays the groundwork for rational inhibitor design and its clinical application, either as monotherapy or in combination treatments for cancer.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulatory compromise as a potential mechanism of fatal hepatic failure during long-term selpercatinib therapy: pharmacokinetic and clinical insights.","authors":"Wataru Suzuki, Yoshito Gando, Junichi Tomomatsu, Yuji Miura, Takeo Yasu, Masakazu Yamaguchi","doi":"10.1007/s00280-026-04942-5","DOIUrl":"https://doi.org/10.1007/s00280-026-04942-5","url":null,"abstract":"<p><p>Selpercatinib is a selective RET inhibitor with established efficacy in RET-altered malignancies; however, data regarding its long-term safety and pharmacokinetic behavior remain limited. We report a case of fatal hepatic failure occurring during prolonged selpercatinib therapy and describe associated clinical and pharmacokinetic findings. A 78-year-old man with RET-mutant medullary thyroid carcinoma received selpercatinib (160 mg twice daily) as second-line therapy following disease progression during vandetanib treatment. After dose interruption and subsequent dose adjustments, the patient achieved a sustained partial response during long-term treatment. Approximately 27 months after selpercatinib initiation, he developed progressive dyspnea, pleural effusion, and severe hepatic dysfunction, ultimately resulting in death. Plasma selpercatinib concentrations were measured during stable disease and later during hepatic decompensation. Pharmacokinetic analysis indicated that drug exposure during the stable treatment period was within the anticipated range, suggesting that elevated drug concentrations observed at the time of hepatic decompensation represented a consequence of impaired clearance rather than a primary cause. These findings implicate circulatory compromise as a potential mediating mechanism and highlight the importance of cardiovascular as well as hepatic monitoring during prolonged selpercatinib therapy. This case highlights a potential indirect mechanism of severe hepatic failure during long-term selpercatinib therapy, in which circulatory compromise-potentially mediated by selpercatinib-associated cardiovascular effects-may have contributed to congestive hepatic decompensation rather than direct drug-induced hepatotoxicity. These findings underscore the importance of integrating cardiovascular surveillance with hepatic monitoring during prolonged selpercatinib treatment.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic and pharmacodynamic sub-study of trans-arterial vs. intravenous gemcitabine in the TIGeR-PaC phase 3 clinical trial.","authors":"Paula M Novelli, Emmanuel E Zervos, Amer H Zureikat, Michael J Pishvaian, Kenneth Meredith, Hassan Hatoum, Reza Nazemzadeh, Sandeep Laroia, Pashtoon Kasi, Justus Bingham, Ramtin Agah","doi":"10.1007/s00280-026-04939-0","DOIUrl":"10.1007/s00280-026-04939-0","url":null,"abstract":"<p><strong>Purpose: </strong>Localized intra-arterial delivery of gemcitabine (IAG) may provide advantages in terms of increased tissue concentration and decreased systemic dosing. We hypothesized IAG may result in decreased systemic gemcitabine concentration and associated side effects due to intracellular delivery prior to conversion to gemcitabine's inactive metabolite, difluorodeoxyuridine (dFdU). Here we report the results of a pharmacokinetics and pharmacodynamics sub-study within the TIGeR-PaC phase 3 clinical trial (NCT03257033).</p><p><strong>Methods: </strong>Analyses were performed for 16 participants across 6 TIGeR-PaC study sites; 11 participants received localized IAG and 5 participants received systemic intravenous gemcitabine (IVG). Gemcitabine and dFdU assays were performed on blood samples collected immediately before, during, and after infusion. CA 19 - 9 levels were measured prior to and 2 weeks after IAG treatment. Maximum plasma drug concentration (C_max) and the area under the drug plasma concentration curve (AUC_0-t) were compared between treatment groups. Pearson's correlation for AUC_0-t and the percent change in CA 19 - 9 levels was calculated for the IAG group.</p><p><strong>Results: </strong>IAG resulted in lower gemcitabine C_max and AUC_0-t and higher dFdU C_max and AUC_0-t compared to IVG, consistent with a more rapid conversion of gemcitabine to dFdU with IAG versus IVG. With IAG, there was a significant correlation between increased dFdU levels and a pre- to post-treatment reduction in CA 19 - 9 levels (Pearson's r = -0.75; P = 0.034).</p><p><strong>Conclusion: </strong>In addition to providing increased local potency, localized IAG, in which gemcitabine is rapidly converted to its inactive metabolite dFdU, may also be beneficial in decreasing gemcitabine-related systemic side effects.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CDCP1-targeted antibody-drug conjugates and immunocytokines for cancer therapy.","authors":"Guangmao Mu, Mingcan Yu, Fulai Zhou, Honglei Bi, Zhengxia Zha, Sheng Huang, Ying Jin, Chao Han, Mark L Chiu, Di Zhang","doi":"10.1007/s00280-026-04941-6","DOIUrl":"https://doi.org/10.1007/s00280-026-04941-6","url":null,"abstract":"<p><strong>Purpose: </strong>CUB domain-containing protein 1 (CDCP1) is an emerging tumor-associated surface antigen broadly expressed in solid tumors and linked to poor prognosis, making it an attractive target for selective therapeutic delivery. We evaluated CDCP1 as a platform for two distinct therapeutic modalities: an antibody-drug conjugate (ADC) for cytotoxic payload delivery and an immunocytokine for targeted delivery of interferon-α2b (IFNα2b).</p><p><strong>Methods: </strong>Novel humanized anti-CDCP1 monoclonal antibodies were generated and characterized for binding to recombinant and cell-surface CDCP1. CDCP1 expression in tumor cells and xenografts was assessed by flow cytometry and immunohistochemistry. CDCP1-targeted ADCs and CDCP1-targeted IFNα2b fusion proteins, including attenuated IFNα2b variants, were evaluated for in vitro cytotoxicity and in vivo antitumor activity in multiple solid tumor xenograft models. A murine cross-reactive anti-CDCP1 ADC was further assessed in an acute mouse toxicity study.</p><p><strong>Results: </strong>CDCP1 was broadly expressed across multiple solid tumor cell lines and xenografts. CDCP1-targeted ADCs mediated potent, target-dependent cytotoxicity in vitro, and MMAE-conjugated ADCs showed robust antitumor activity in pancreatic, lung, breast, and colon xenograft models, with tumor growth inhibition up to 90%. Antibodies recognizing the proteolyzed amino-terminal region of CDCP1 also retained in vivo activity. The murine cross-reactive ADC was well tolerated in an acute toxicity study. CDCP1-targeted IFNα2b fusion proteins displayed markedly enhanced potency against CDCP1-positive tumor cells versus a non-targeted control, and IFNα2b attenuation enabled tunable cytokine activity. In a human PBMC-supported BxPC-3 model, a CDCP1-targeted IFNα2b immunocytokine achieved significant tumor growth inhibition.</p><p><strong>Conclusion: </strong>These findings established CDCP1 as a versatile therapeutic target and supported further development of parallel CDCP1-targeted ADC and immunocytokine strategies for solid tumors.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase 1, open-label study evaluating the pharmacokinetics, safety, and tolerability of vepdegestrant in Chinese patients with ER+/HER2- advanced breast cancer.","authors":"Binghe Xu, Jin Yang, Pin Zhang, Wenna Wang, Liang Zhang, Xiao'ai Zhao, Fei Guan, Naihan Chen, Huadong Zhao, Cong Fei","doi":"10.1007/s00280-026-04921-w","DOIUrl":"https://doi.org/10.1007/s00280-026-04921-w","url":null,"abstract":"<p><strong>Purpose: </strong>Vepdegestrant is an investigational, orally administered PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader being evaluated for the treatment of ER+/HER2- advanced breast cancer, with promising results in prior studies of Western and Japanese patients. Vepdegestrant had not been previously evaluated in Chinese patients.</p><p><strong>Methods: </strong>This phase 1 study (NCT05732428) assessed pharmacokinetics (PK) of vepdegestrant and its epimer (ARV-473), and safety and preliminary efficacy of vepdegestrant monotherapy (200 mg once daily [QD] in 28-day cycles) in Chinese adults with ER+/HER2- advanced breast cancer who had received ≥ 1 prior line of endocrine therapy.</p><p><strong>Results: </strong>Nine female Chinese patients were treated (median age, 56.0 [range: 42.0-69.0] years; six received ≥ 3 prior anticancer therapies in the advanced setting). Geometric mean area under the plasma concentration-time curve over the dosing interval was 9575 ng*h/mL following a single dose and 18,340 ng*h/mL following multiple daily doses on day 15; maximum observed concentration of vepdegestrant was 633.2 ng/mL and 1035 ng/mL after single and multiple doses, respectively. Vepdegestrant was well tolerated. Most treatment-related adverse events (TRAEs) were grade 1 or 2. Two patients experienced grade 3 TRAEs; no patients discontinued due to AEs. Objective response and clinical benefit rates were 33.3% and 44.4%, respectively. Three patients had partial responses; all three subsequently had progressive disease at the final data cutoff.</p><p><strong>Conclusions: </strong>Vepdegestrant (200 mg QD) demonstrated a PK profile comparable to previous studies, a well-tolerated safety profile, and signs of preliminary antitumor activity in heavily pretreated Chinese patients with ER+/HER2- advanced breast cancer.</p><p><strong>Clinical trial registration number: </strong>ClinicalTrials.gov ID, NCT05732428.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of body composition with neoadjuvant chemotherapy response, toxicity, and prognosis in breast cancer: a scoping review.","authors":"Samantha Ligertwood, Femi E Ayeni, Andrew Parsonson, Senarath Edirimanne","doi":"10.1007/s00280-026-04940-7","DOIUrl":"10.1007/s00280-026-04940-7","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the leading cause of cancer-related death in women worldwide. There is increasing interest in using detailed body composition parameters, such as skeletal muscle mass and adiposity, to better predict treatment response, toxicity, and survival in breast cancer patients receiving neoadjuvant chemotherapy (NAC). This study synthesised current literature on the effect of body composition in breast cancer patients undergoing NAC and identified gaps for future research.</p><p><strong>Methods: </strong>A scoping review was conducted in accordance with PRISMA-ScR and Arksey & O'Malley frameworks. Embase, MEDLINE, PubMed, and Google Scholar were searched for studies published between 2010 and 2025 to map available evidence. Eligible studies included female breast cancer patients receiving NAC with body composition assessment and at least one outcome of response, toxicity, or prognosis.</p><p><strong>Results: </strong>Twenty studies met inclusion criteria. Computed tomography at the L3 vertebral level was the most common assessment method. Findings were heterogeneous; 3 studies reported a statistically significant association between sarcopenia and reduced pathological response, while results for adiposity were inconsistent. Half of the studies assessing toxicity reported higher toxicity rates in patients with sarcopenia and/or adiposity. Prognostic findings were variable, with some studies reporting associations with visceral adiposity, and only one study reporting a significant association with sarcopenia.</p><p><strong>Conclusions: </strong>Evidence regarding the relationship between adiposity and NAC toxicity and prognosis in breast cancer remains suggestive, while findings for sarcopenia are inconsistent. Prospective, standardised studies are needed to clarify the role of body composition in breast cancer outcomes and its relevance in treatment planning.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologically based pharmacokinetic modeling to predict human pharmacokinetics of a novel mithramycin analog for Ewing sarcoma.","authors":"Kumar Kulldeep Niloy, Jamie Horn, Nazmul Hasan Bhuiyan, Suhas S Bhosale, Khaled A Shaaban, Thomas E Prisinzano, Jon S Thorson, Jurgen Rohr, Markos Leggas","doi":"10.1007/s00280-026-04935-4","DOIUrl":"10.1007/s00280-026-04935-4","url":null,"abstract":"<p><strong>Purpose: </strong>To develop and qualify a physiologically based pharmacokinetic (PBPK) modeling strategy for mithramycin (MTM) and its analog, MTMSA-Trp, with the aim of projecting first-in-human plasma pharmacokinetics and supporting the translational development of MTMSA-Trp for Ewing sarcoma treatment.</p><p><strong>Methods: </strong>PBPK models were created in GastroPlus^® using a middle-out approach, incorporating preclinical pharmacokinetic data from mice, rats, and cynomolgus monkeys. Human clearance was estimated through three methods: an additional clearance approach, allometric scaling, and single-species scaling from monkeys. The model was evaluated using clinical MTM plasma PK data and then employed to project human MTMSA-Trp plasma PK, with tissue predictions considered exploratory to contextualize hepatotoxicity risk.</p><p><strong>Results: </strong>The additional clearance approach provided the most accurate prediction of human MTM plasma PK. Across all clearance prediction methods, MTMSA-Trp was predicted to achieve 8- to 15-fold higher human plasma exposure than MTM at the same dose. Model-derived liver exposures were 2- to 4-fold higher, with a lower predicted liver partition for MTMSA-Trp; however, these tissue predictions remained sensitive to distribution assumptions. Parameter sensitivity analysis identified the blood-to-plasma ratio as the most influential parameter among those examined.</p><p><strong>Conclusion: </strong>PBPK modeling supports the projection that MTMSA-Trp will achieve substantially higher plasma exposure than MTM in humans. This empirically developed workflow may inform translational efforts for the first-in-human development of MTMSA-Trp.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative characterization of platelet count and alanine aminotransferase dynamics to inform personalized dosing in the first-in-human LP-184 trial.","authors":"Jianli Zhou, Daruka Mahadevan, Jay Parekh, Marc Chamberlain, Kishor Bhatia, Reginald Ewesuedo","doi":"10.1007/s00280-026-04937-2","DOIUrl":"10.1007/s00280-026-04937-2","url":null,"abstract":"<p><strong>Purpose: </strong>Safety evaluation in first-in-human (FIH) Phase 1 oncology trials is largely descriptive and provides limited quantitative insights. This study characterized the dynamics of platelet count (PLT) and alanine aminotransferase (ALT) concentration in the LP-184 FIH study and explored statistical modeling to support personalized dosing strategies.</p><p><strong>Methods: </strong>PLT and ALT data were analyzed to characterize temporal trends, inter-patient variability, and correlations with baseline characteristics and exposure. Firth logistic regression was fitted to identify potential contributors to clinically relevant PLT abnormalities.</p><p><strong>Results: </strong>PLT nadir predominantly occurred in cycle 2, with baseline PLT and total single-infusion dose as critical contributors. Patients with baseline PLT below 200 K/µL were at high risk of developing grade ≥ 2 PLT decreased adverse events. ALT levels mostly peaked in cycle 1, with a moderate association with dose and no evident relationship to baseline liver metastases. Patients with glioblastoma exhibited a higher probability of experiencing ALT increased events at grade ≥ 2. A single infusion dose above 40 mg was associated with increased occurrence of high-grade PLT decreased and ALT increased events. A personalized dose recommendation strategy is proposed.</p><p><strong>Conclusion: </strong>Integration of in-depth data analytics in FIH studies facilitates earlier safety signal detection and informs safety monitoring and dose selection in later studies.</p><p><strong>Registry: </strong>ClinicalTrials.gov, TRN: NCT05933265, Registration date: 23 June 2023.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse events of cetuximab sarotalocan in photoimmunotherapy: insights from the Japanese adverse drug event report database.","authors":"Shiho Ueta, Takahiro Niimura, Sakura Fujino, Mitsuhiro Goda, Tomoaki Ishida, Hideki Nawa, Emika Kawata, Kaito Tsujinaka, Kei Kawada, Koji Miyata, Io Horikawa, Fuka Aizawa, Kenta Yagi, Masayuki Chuma, Yuki Izawa-Ishizawa, Keisuke Ishizawa","doi":"10.1007/s00280-026-04929-2","DOIUrl":"10.1007/s00280-026-04929-2","url":null,"abstract":"<p><strong>Purpose: </strong>Cetuximab sarotalocan is an innovative photoimmunotherapy agent for cancer treatment, with an unclear safety profile. We analysed the clinical adverse event profile of cetuximab sarotalocan in photoimmunotherapy.</p><p><strong>Methods: </strong>In this retrospective study, we analysed real-world clinical data of patients with head and neck cancer from the Japanese Adverse Drug Event Report database. Patient demographics, as well as the nature of adverse events and their outcomes and co-occurrences, were analysed.</p><p><strong>Results: </strong>Cetuximab sarotalocan adverse event reports (n = 227) predominantly included older male patients. The most frequent adverse event was laryngeal oedema, followed by upper respiratory and oral complications. Recovery rates were high for laryngeal oedema and tongue-related adverse events but poor for fistula-related complications. Co-occurrence was found between different adverse events, particularly laryngeal oedema and dysphagia.</p><p><strong>Conclusion: </strong>The described safety profile of cetuximab sarotalocan in photoimmunotherapy offers insights for its proper use as well as baseline data for the development and improvement of cancer photoimmunotherapy.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}