Cancer Chemotherapy and Pharmacology最新文献

{"title":"Antitumor efficacy and reduced systemic toxicity of palmitic acid-modified pirarubicin nanoparticles in mice.","authors":"Kenji Tsukigawa, Takashi Hasegawa, Kindness Lomotey Commey, Shuhei Imoto, Koji Nishi, Masaki Otagiri, Keishi Yamasaki","doi":"10.1007/s00280-026-04905-w","DOIUrl":"10.1007/s00280-026-04905-w","url":null,"abstract":"<p><strong>Purpose: </strong>Pirarubicin (THP) is a potent anthracycline anticancer agent; however, its clinical use is limited by nonselective tissue distribution and systemic toxicity. This study aimed to evaluate whether palmitic acid-modified THP nanoparticles (Pal-THP nanoparticles) could improve the in vivo therapeutic profile of THP.</p><p><strong>Methods: </strong>Pal-THP nanoparticles stabilized by albumin as a formulation stabilizer were prepared by antisolvent precipitation. Antitumor efficacy, biodistribution, and drug forms (intact Pal-THP and the free THP released from Pal-THP) were evaluated in colon 26 tumor-bearing mice following intravenous administration. Acute systemic and hemolytic toxicity were assessed relative to THP.</p><p><strong>Results: </strong>Pal-THP nanoparticles significantly suppressed tumor growth compared with the control group, without inducing body weight loss, whereas THP exhibited a tendency toward tumor suppression but did not reach statistical significance versus control at an equivalent dose. While the absolute tumor accumulation of Pal-THP nanoparticles was limited, it was significantly higher than that of THP. Importantly, there was efficient conversion of Pal-THP to free THP in tumor tissue, which is consistent with the presence of an acid‑labile hydrazone linkage. Pal-THP nanoparticles also markedly attenuated acute systemic and hemolytic toxicity, in contrast to THP, under the present experimental conditions.</p><p><strong>Conclusion: </strong>Pal-THP nanoparticles altered the in vivo fate of THP through tumor accumulation and tumor-localized conversion to free THP. This resulted in effective tumor suppression and a significant reduction in toxicity compared to THP in mice. Thus, this formulation strategy represents a promising approach for improving the therapeutic index of chemotherapy using THP and other anthracyclines.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970599","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":"Transfer of trastuzumab and pertuzumab into human breast milk: a case report.","authors":"Pauline L M Buitelaar, Dick Pluim, Sandy Hanssens, Yohan Kerbage, Hilde Rosing, Alwin D R Huitema, Frédéric C Amant","doi":"10.1007/s00280-026-04901-0","DOIUrl":"10.1007/s00280-026-04901-0","url":null,"abstract":"<p><strong>Purpose: </strong>Lactation could offer benefit to the mother and child. Information on the safety of lactation during anti-cancer treatment, however, is scarce. Therefore, clinical data about drug exposure through breast milk is needed. To contribute to this, we present a case of a 34-year old woman who was treated with intravenous trastuzumab 600 mg and pertuzumab 1200 mg in the first cycle. Over the first 17 days of treatment, she collected breast milk samples.</p><p><strong>Methods: </strong>Trastuzumab and pertuzumab concentrations in breast milk were determined by validated ELISAs. Subsequently, infant exposure parameters such as infant daily dose (IDD), relative infant dose (RID), and cumulative RID were calculated.</p><p><strong>Results: </strong>The cumulative RID was 16.8% for trastuzumab and 24.3% for pertuzumab. Based on our results, we can conclude that intravenously administered trastuzumab and pertuzumab transfer into breast milk exceeding the safety threshold of an RID of 10%.</p><p><strong>Conclusion: </strong>Although the extent of systemic exposure in infants after ingestion of breast milk containing these monoclonal antibodies is unknown, systemic exposure cannot be excluded. Therefore, breastfeeding during treatment with trastuzumab and pertuzumab should be discouraged.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13190791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970678","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":"Failure of a LHRH agonist in metastatic prostate cancer: a case report and review of literature.","authors":"Eleonora Paganoni, Paola Sabbadini, Antonio D'Avolio, Jessica Cusato, Giovanna Motta, Letizia Galeasso, Roberto Filippi, Massimo Di Maio, Ilaria Depetris","doi":"10.1007/s00280-026-04903-y","DOIUrl":"10.1007/s00280-026-04903-y","url":null,"abstract":"<p><strong>Background: </strong>Androgen deprivation therapy (ADT) is the cornerstone of advanced prostate cancer treatment, aiming to achieve castrate testosterone levels. Luteinizing hormone-releasing hormone (LHRH) agonists are widely used, but intrinsic resistance, although rare, may pose significant therapeutic challenges.</p><p><strong>Case presentation: </strong>We report a 75-year-old man with de novo low-volume metastatic prostate cancer who experienced unusual refractoriness to LHRH agonist therapy. Despite correct administration of leuprolide and good treatment adherence, testosterone levels did not drop and instead progressively increased over five months. This occurred concurrently with a marked PSA decline following the addition of the androgen receptor pathway inhibitor (ARPI) apalutamide. Drug-drug interactions, pharmacological interference, and other common causes of treatment resistance were ruled out. Upon switching to the LHRH antagonist degarelix, adequate testosterone suppression was rapidly achieved.</p><p><strong>Discussion: </strong>This case highlights a rare biochemical failure of LHRH agonist therapy, possibly due to primary resistance or inadequate receptor desensitization. The concomitant use of an ARPI masked ADT failure by suppressing PSA despite elevated testosterone. This case emphasizes the still relevant need for periodic testosterone monitoring to ensure effective hormonal suppression.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970668","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":"The hidden impact of renal impairment on ribociclib exposure and co-medications: a case report.","authors":"Manon Launay, Alicja Puszkiel, Thomas Genevee, Audrey Bellesoeur, Michael Bringuier","doi":"10.1007/s00280-026-04904-x","DOIUrl":"10.1007/s00280-026-04904-x","url":null,"abstract":"<p><strong>Background: </strong>Ribociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, is widely used in combination with endocrine therapy for advanced hormone receptor-positive breast cancer. However, drug exposure may be highly variable in older patients due to organ dysfunction and polypharmacy, raising the need for therapeutic drug monitoring (TDM).</p><p><strong>Case presentation: </strong>We report the case of an 88-year-old woman with metastatic lobular breast carcinoma treated with ribociclib and tamoxifen, who developed progressive renal impairment and was co-prescribed apixaban. Serial TDM demonstrated ribociclib overexposure (Cmin 1022-1318 ng/mL vs. ~ 500 ng/mL expected at steady state), associated with markedly increased plasma concentrations of tamoxifen, endoxifen, and apixaban (923 ng/mL vs. reference peak ~ 206 ng/mL). Monte Carlo simulations incorporating patient covariates confirmed that measured ribociclib concentrations exceeded predicted distributions, likely due to the accumulation of uremic toxins.</p><p><strong>Conclusion: </strong>TDM of CDK4/6 inhibitors provides valuable insight into drug exposure in complex geriatric oncology settings. Beyond monitoring ribociclib itself, this approach facilitates a broader discussion on individualized dosing, comedication safety, and management of organ dysfunction in elderly patients with cancer.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970650","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":"Physiologically based pharmacokinetic modeling of granisetron for optimizing antiemetic therapy in patients with cancer: multi-route pharmacokinetic characterization and target-site exposure prediction.","authors":"Ji-Hun Jang, Seung-Hyun Jeong","doi":"10.1007/s00280-026-04900-1","DOIUrl":"10.1007/s00280-026-04900-1","url":null,"abstract":"<p><strong>Background: </strong>Granisetron, a selective 5-hydroxytryptamine type 3 (5-HT₃) receptor antagonist, is widely used for the prevention and treatment of chemotherapy-induced nausea-vomiting in patients with cancer. However, quantitative data describing differences in in vivo pharmacokinetics (PK) among available formulations, including intravenous, oral, subcutaneous, and transdermal patches, and comparative drug concentrations at pharmacological target tissues, such as the central chemoreceptor trigger zone and enterovagal nerve terminals, remain limited.</p><p><strong>Purpose: </strong>This study aimed to develop a whole-body physiologically based pharmacokinetic (PBPK) model to predict systemic and pharmacological target tissue concentrations of granisetron across multiple routes of administration and to elucidate route-specific PK and target-tissue exposure characteristics to support optimization of antiemetic therapy.</p><p><strong>Methods: </strong>A PBPK model was developed using literature-derived clinical PK data integrated with human physiological parameters and relevant in vitro data. The model was calibrated and validated against single-dose and multiple-dose clinical datasets. Predictive performance was evaluated using the ratio of model-predicted values ​​to observed values ​​and the proportion of observed data captured within prediction intervals. Subsequently, granisetron concentrations in pharmacological target tissues were simulated at clinically relevant doses for each route of administration.</p><p><strong>Results: </strong>The PBPK model accurately reproduced plasma concentration-time profiles for all administration routes and demonstrated acceptable predictive accuracy for key PK parameters. Tissue-level simulations showed that intravenous and oral administration produced rapid and high central exposure, with oral administration reflecting rapid gastrointestinal absorption into the systemic circulation. In contrast, the transdermal patch provided sustained and stable central and peripheral exposure, whereas subcutaneous administration yielded prolonged systemic exposure compared with intravenous and oral dosing, resulting in intermediate systemic and target-tissue exposure. Distinct tissue exposure profiles and exposure durations were observed for each formulation.</p><p><strong>Conclusion: </strong>This study provides the first PBPK-based quantitative characterization of granisetron PK and target-tissue exposure across clinically relevant routes of administration. The findings support route-specific optimization of antiemetic therapy according to patient characteristics and clinical context. Furthermore, the developed model may facilitate personalized supportive care in oncology, including applications in vulnerable populations (e.g., older adults, individuals with hepatic impairment, pregnant patients), as well as formulation development research.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970604","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":"Enhancing triapine treatment: strategies for dose optimization and methemoglobin level mitigation.","authors":"Heekyung Lee, Allison Dunn, Sarah E Taylor, Aman Chauhan, S Percy Ivy, Jogarao Gobburu, Jan H Beumer","doi":"10.1007/s00280-026-04898-6","DOIUrl":"10.1007/s00280-026-04898-6","url":null,"abstract":"<p><strong>Purpose: </strong>Triapine is a potent small-molecule ribonucleotide reductase inhibitor investigated in combination with radiation and/or chemotherapy for the treatment of advanced stage solid cancers. The aim of this study is to develop a population pharmacokinetic-pharmacodynamic (PK/PD) model for triapine to describe the PK parameters, the effect of smoking on exposure, and the relationship between methemoglobin concentrations and exposure.</p><p><strong>Methods: </strong>A total of 36 patients with advanced stage cervical or neuroendocrine cancers from two phase I studies were included in the population PK/PD model building. Triapine and methemoblogin plasma concentrations were sampled over an 8-hr or 24-hour period. Data were analyzed by a nonlinear mixed-effects modelling approach. Simulations were performed to optimize the dosing strategy for oral triapine.</p><p><strong>Results: </strong>A two-compartment model with two-transit compartment Erlang absorption and first-order elimination best described the PK of triapine, and an effect compartment model best described the PD effect of triapine on methemoglobin concentrations. The final model described triapine PK/PD well, and a 38% increase in triapine clearance was estimated due to smoking. Simulations suggest that dose adjustments may be necessary, as increasing the oral dose for smokers from 100 to 125 mg resulted in exposures matching those observed in nonsmokers.</p><p><strong>Conclusion: </strong>This study provides a quantitative model characterizing the relationship between triapine exposure and methemoglobin concentrations. The developed PK/PD model can be used to optimize the dosing regimen for oral triapine, illustrating how population PK/PD modeling can inform decision-making throughout the triapine drug development lifecycle.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13190473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970601","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":"Pharmacokinetic and pharmacogenomic profile of capecitabine and oxaliplatin in a patient with gastric cancer undergoing hemodialysis: a case report.","authors":"Yuki Nakano, Toshinori Hirai, Nao Nishijo, Yugo Uematsu, Yoko Nakajima, Tomomi Ozaki, Ryoko Shibata, Asako Imada, Kazuya Naritomi, Fumihiko Ogata, Naohito Kawasaki, Tadashi Hayama, Masafumi Yasunaga, Kazuhiro Tada, Hirotsugu Hasuwa, Kosuke Masutani","doi":"10.1007/s00280-026-04899-5","DOIUrl":"10.1007/s00280-026-04899-5","url":null,"abstract":"<p><strong>Purpose: </strong>Anticancer therapy for patients with gastric cancer on hemodialysis is challenging owing to varying pharmacokinetics and a lack of clinical trial data. This study aimed to evaluate the efficacy and safety of the capecitabine plus oxaliplatin (CapeOX) regimen in a 73-year-old male Japanese patient with stage IV gastric cancer (human epidermal growth factor receptor 2 negative) undergoing hemodialysis.</p><p><strong>Methods: </strong>The selected chemotherapy regimen was approximately 50% dose of CapeOX (capecitabine 1500 mg/day on days 1-14 and oxaliplatin 100 mg/day 2-h infusion on day 1) every 3 weeks. Data on plasma drug concentrations, metabolic enzyme genetic polymorphisms, and clinical outcomes were analyzed.</p><p><strong>Results: </strong>Anticancer therapy initially controlled the tumor; however, disease progression and cumulative peripheral neuropathy led to discontinuation after 17 cycles (approximately 12 months of treatment). Oxaliplatin exhibited a rebound increase after each dialysis session (dialyzer clearance [CL_dial]: median, 44.12 [interquartile range {IQR}: 24.89 - 70.08] mL/min; hemodialysis removal rate: median, 35.98% [IQR: 19.63 - 54.45]. α-fluoro-β-alanine, the final metabolite of capecitabine, accumulated substantially, although approximately half of them was removed by hemodialysis (CL_dial: median, 61.32 [IQR: 24.89 - 70.08] mL/min; hemodialysis removal rate: median, 47.98% [IQR: 44.74 - 50.29]). The UPB1 intronic variant and a DPYD missense mutation (1627 A > G) were detected. The DPYD variant likely influenced 5-fluorouracil metabolism, as its area under the concentration-time curve from 0 to 12 h was comparable to the standard dosage.</p><p><strong>Conclusion: </strong>These findings suggest that appropriate dose reduction and genetic screening might be considered part of chemotherapy guidance to improve safety and effectiveness for patients with advanced gastric cancer undergoing hemodialysis.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926600","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":"Targeting the GSK-3β/mTOR axis to overcome chemoresistance in gestational choriocarcinoma: molecular mechanisms and therapeutic opportunities.","authors":"Marwan Al-Hajeili, Hayder M Al-Kuraishy, Ahmed M Abdelaziz, Gaber El-Saber Batiha","doi":"10.1007/s00280-026-04896-8","DOIUrl":"10.1007/s00280-026-04896-8","url":null,"abstract":"<p><p>Gestational choriocarcinoma represents one of the most curable solid tumors when diagnosed early, with cure rates exceeding 95% using standard chemotherapy. However, a subset of patients develops chemoresistance, leading to treatment failure and poor outcomes. Emerging evidence indicates that aberrant activation of the glycogen synthase kinase-3β (GSK-3β)/mechanistic target of rapamycin (mTOR) signaling axis is strongly associated with chemoresistance through multiple interconnected mechanisms. This review examines the molecular pathways by which GSK-3β and mTOR likely contribute to chemoresistance in gestational choriocarcinoma, including enhanced epithelial-mesenchymal transition (EMT), metabolic reprogramming, immune evasion, autophagy dysregulation, and suppression of apoptosis. We analyze how crosstalk between GSK-3β and mTOR complexes (mTORC1/mTORC2) creates a resistant phenotype that limits the efficacy of conventional cytotoxic agents such as methotrexate, actinomycin D, and etoposide. Importantly, we highlight emerging therapeutic strategies to target this axis, including GSK-3β activators (lithium, 9-ING-41), mTOR inhibitors (rapamycin analogs, dual PI3K/mTOR inhibitors), and combination regimens that synergistically restore chemosensitivity. Preclinical data from trophoblastic and related malignancies demonstrate that dual targeting of GSK-3β and mTOR can reverse resistance phenotypes and enhance treatment responses. This comprehensive review provides a translational framework for developing molecularly targeted therapies in chemoresistant gestational choriocarcinoma, with potential implications for personalized treatment algorithms and clinical trial design in this rare but highly treatable malignancy.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873463","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":"Characterizing P-glycoprotein and Breast Cancer Resistance Protein interactions of asciminib among other tyrosine kinase inhibitors used in chronic myeloid leukemia.","authors":"N E Verhagen, D C W Touw, J J M W van den Heuvel, P H van den Broek, N M A Blijlevens, J J W M Janssen, J B Koenderink, F G M Russel","doi":"10.1007/s00280-026-04891-z","DOIUrl":"10.1007/s00280-026-04891-z","url":null,"abstract":"<p><p>The distribution of tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukemia (CML) is influenced by the efflux transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). While most TKI-transporter interactions are well established, limited information is available for the novel STAMP inhibitor asciminib, and divergent data exist for the role of P-gp in nilotinib and bosutinib efflux. This study used in vitro cellular and vesicular transport assays to evaluate the substrate and inhibitory profiles of all TKIs currently used in CML treatment. It was confirmed that asciminib is a substrate of both P-gp and BCRP, similar to imatinib and dasatinib, whereas bosutinib was modestly transported by P-gp only. For P-gp, asciminib appeared to be a weak inhibitor, comparable to dasatinib, whereas nilotinib remained the most potent inhibitor. Conversely, asciminib demonstrated notable potency against BCRP, ranking it among the strong inhibitors imatinib, nilotinib, and ponatinib, while dasatinib and bosutinib were less effective. These findings provide further insight into the efflux transporter interactions of asciminib and updated evidence on nilotinib and bosutinib transport by P-gp, with implications for drug resistance and treatment optimization in CML.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13167888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873422","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":"Oxaliplatin-associated nephrotoxicity: clinical patterns, renal pharmacokinetics, and mechanistic insights.","authors":"Ananya Chetia, Leena Das, Momita Rani Baro, Manas Das","doi":"10.1007/s00280-026-04889-7","DOIUrl":"10.1007/s00280-026-04889-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>OXA, a third-generation platinum-based chemotherapeutic agent widely used in gastrointestinal malignancies, is generally regarded as less nephrotoxic than earlier platinum compounds such as cisplatin. However, growing clinical reports and mechanistic studies indicate that renal injury can occur in a subset of patients and may be underrecognized. This review aims to synthesize current evidence on OXA-associated renal dysfunction by integrating clinical patterns of injury with pharmacokinetic behavior and mechanistic pathways relevant to kidney toxicity.</p><p><strong>Methods: </strong>A focused literature search was conducted in PubMed, Google Scholar, and ScienceDirect for studies published up to December 10, 2025, using keywords related to OXA and renal injury. Additional relevant publications were identified through citation tracking using ResearchRabbit. Records were screened and managed using Rayyan, with duplicate removal performed prior to eligibility assessment. Clinical reports, observational studies, and experimental investigations evaluating renal outcomes following OXA exposure were included, while non-original articles, non-English publications, studies lacking renal assessment, and reports with major confounding nephrotoxic therapies were excluded.</p><p><strong>Results: </strong>Evidence indicates that OXA-associated nephrotoxicity, although less frequent than cisplatin-induced injury, is clinically relevant. Reported manifestations include AKI, acute tubular necrosis, proximal tubular dysfunction, immune-mediated hemolysis with pigment nephropathy, and tubulointerstitial nephritis. Mechanistic studies implicate transporter-mediated renal handling, oxidative stress, inflammatory signaling, DNA damage responses, and segment-specific tubular vulnerability. Pharmacokinetic factors, cumulative exposure, combination regimens, and pre-existing renal impairment further influence susceptibility.</p><p><strong>Conclusion: </strong>OXA cannot be considered entirely free from renal adverse effects. Improved clinical vigilance, mechanistic insight, and risk-adapted monitoring strategies are essential to optimize patient safety while maintaining therapeutic efficacy.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873379","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}