Cancer Chemotherapy and Pharmacology最新文献

{"title":"Predictive factors for first dose reduction and interruption of lenvatinib after beginning of the standard dose in Japanese patients with thyroid cancer.","authors":"Kazuma Fujita, Mitsuji Nagahama, Akifumi Suzuki, Chie Masaki, Kiminori Sugino, Koichi Ito, Masatomo Miura","doi":"10.1007/s00280-024-04729-6","DOIUrl":"10.1007/s00280-024-04729-6","url":null,"abstract":"<p><strong>Purpose: </strong>The associations between first dose reduction or interruption by side effects and lenvatinib plasma trough concentration (C₀) after administration of a starting dose of 24 mg in 70 Japanese patients with thyroid cancer were evaluated.</p><p><strong>Methods: </strong>Plasma samples were collected each week for 1 month and at the first incidence of side effects leading to dose reduction or interruption after beginning administration of 24 mg lenvatinib.</p><p><strong>Results: </strong>The area under the receiver operating characteristic curve was 0.789 at a lenvatinib C₀ threshold of 128.25 ng/mL for predicting the first dose reduction or interruption. The median time to the first dose reduction or interruption was 14.0 days in patients with a C₀ of ≥ 128.25 ng/mL and 21.0 days in those with a C₀ of < 128.25 ng/mL (P = 0.001). At one, two, three and four weeks respectively, the first dose reduction or interruption was associated with body weight (P = 0.034); sex (P = 0.021); sex, age, and lenvatinib C₀ of ≥ 128.25 ng/mL (P = 0.025, 0.024, and 0.048, respectively); and age and lenvatinib C₀ of ≥ 128.25 ng/mL (each P = 0.004).</p><p><strong>Conclusions: </strong>On day 8 after administration of 24 mg lenvatinib, lenvatinib dose may be adjusted based on the target C₀ of 128.25 ng/mL to maintain a high dose intensity during this early phase; however, because persistence of a higher C₀ of 128.25 ng/mL causes early dose interruption or reduction, prospective dose reduction based on the next lower target C₀ for the maintenance phase may be necessary.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"8"},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863461","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":"Intrathecal pemetrexed for leptomeningeal metastases in a patient with ALK-rearranged lung adenocarcinoma: a case report.","authors":"Emelie Gezelius, Maria Planck, Bassam Hazem, Seema Nagpal, Heather Wakelee","doi":"10.1007/s00280-024-04735-8","DOIUrl":"10.1007/s00280-024-04735-8","url":null,"abstract":"<p><p>Progressive leptomeningeal metastases (LM) are associated with intractable neurological symptoms and a poor prognosis, and effective treatment options are limited. Intrathecal (IT) pemetrexed has been shown to confer clinical benefit in lung adenocarcinoma, yet our understanding of the efficacy and safety of the treatment is limited. We report a patient with a long-standing history of leptomeningeal disease due to ALK-positive adenocarcinoma of the lung, previously controlled by increased doses of lorlatinib (125 mg/day). Rapid LM progression prompted the start of IT pemetrexed, after which the patient experienced immediate clinical improvement. The case provides additional support that IT pemetrexed can offer symptomatic relief and may be considered as a treatment option in advanced LM. Furthermore, the case illustrates that an increased dose of lorlatinib may efficiently control LM in patients with ALK-rearranged NSCLC, following progression on standard lorlatinib dosage.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"6"},"PeriodicalIF":2.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833917","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":"Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892).","authors":"Sarah E Taylor, Sarah Behr, Kristine L Cooper, Haider Mahdi, Denise Fabian, Holly Gallion, Frederick Ueland, John Vargo, Brian Orr, Eugenia Girda, Madeleine Courtney-Brooks, Alexander B Olawaiye, Leslie M Randall, Debra L Richardson, Stephanie A Sullivan, Marilyn Huang, Susan M Christner, Sushil Beriwal, Yan Lin, Aman Chauhan, Edward Chu, Elise C Kohn, Charles Kunos, S Percy Ivy, Jan H Beumer","doi":"10.1007/s00280-024-04720-1","DOIUrl":"10.1007/s00280-024-04720-1","url":null,"abstract":"<p><strong>Background: </strong>The addition of IV triapine to chemoradiation appeared active in phase I and II studies but drug delivery is cumbersome. We examined PO triapine with cisplatin chemoradiation.</p><p><strong>Methods: </strong>We implemented a 3 + 3 design for PO triapine dose escalation with expansion, starting at 100 mg, five days a week for five weeks while receiving radiation with weekly IV cisplatin for locally advanced cervical or vaginal cancer. Maximum tolerated dose (MTD), dose limiting toxicity (DLT), adverse events, pharmacokinetics (PK), pharmacodynamics (PD), and metabolic complete response (mCR) were assessed.</p><p><strong>Results: </strong>19/21 patients were DLT evaluable. DLTs included grade 4 neutropenia (n = 2), leukopenia (n = 2), lymphopenia (n = 2), and hypokalemia (n = 1). Grade 3 toxicities at least possibly related were as expected for cisplatin chemoradiation: lymphopenia (n = 12), anemia (n = 10), neutropenia (n = 4), leukopenia (n = 8), decreased platelets (n = 2), hypertension (n = 1), and hyponatremia (n = 1). MTD and RP2D were established at 100 mg. 8/13 evaluable patients had a mCR. Triapine had a bioavailability of 59%. Methemoglobin levels correlated with triapine exposure. Smoking almost doubled CYP1A2 mediated triapine clearance.</p><p><strong>Conclusions: </strong>Oral triapine is safe when given with cisplatin chemoradiation, convenient, bioavailable. Exposure is negatively impacted by smoking, and methemoglobin is a biomarker of exposure.</p><p><strong>Clinical trial registration: </strong>NCT02595879.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"4"},"PeriodicalIF":2.7,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823869","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":"Absorption, metabolism, and excretion of oral [¹⁴C] radiolabeled donafenib: an open-label, phase I, single-dose study in humans.","authors":"Sheng Ma, Ling Yi, YiCong Bian, Binhua Lv, Cong Zhang, Chengwei Li, Hua Zhang, Liyan Miao","doi":"10.1007/s00280-024-04725-w","DOIUrl":"10.1007/s00280-024-04725-w","url":null,"abstract":"<p><strong>Purpose: </strong>The study aims to investigate the absorption, metabolism, and excretion of donafenib, a deuterated derivative of sorafenib, in healthy Chinese male volunteers.</p><p><strong>Methods: </strong>Six healthy Chinese male volunteers were administered a single oral dose of 300 mg donafenib containing 120 µCi of [14 C]-donafenib. The study involved collecting and analyzing plasma, urine, and feces samples to determine the recovery and distribution of total radioactivity, identify metabolites, and assess the metabolic pathways of donafenib.</p><p><strong>Results: </strong>The mean recovery of total radioactivity was 97.31% of the administered dose. Six metabolites were identified, with the parent drug being the major radioactive component in plasma (67.52% of total radioactivity) and feces (83.17% of the dose). The N-oxidation metabolite (M2) was prominent in plasma. Donafenib was predominantly excreted via feces, indicating liver metabolism, with minimal renal excretion. The metabolic pathways of donafenib were similar to those of sorafenib, but the metabolite profiles differed significantly. Notably, the amide hydrolysis metabolite M6, present in sorafenib, was absent in donafenib.</p><p><strong>Conclusion: </strong>Donafenib is primarily metabolized in the liver and excreted through feces, with a metabolic profile that differs from sorafenib due to the deuterium isotope effect. These differences in metabolic characteristics may contribute to donafenib's improved safety and efficacy as a treatment for advanced hepatocellular carcinoma (HCC).</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"5"},"PeriodicalIF":2.7,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823867","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":"Sulforaphane inhibits multiple myeloma cell-induced osteoclast differentiation and macrophage proliferation by elevating ferroportin1.","authors":"Weichu Sun, Jingqi Sun, Wei Hu, Cong Luo, Zhongwei Lu, Fen He, Hongyan Zhao, Xi Zeng, Deliang Cao, Junjun Li, Chang Zhang, Jiliang Xia","doi":"10.1007/s00280-024-04736-7","DOIUrl":"https://doi.org/10.1007/s00280-024-04736-7","url":null,"abstract":"<p><strong>Purpose: </strong>Osteolysis is a common complication in patients with multiple myeloma (MM). Our previous studies have demonstrated that MM cells can promote osteoclast differentiation of macrophages. In this study, we explored the effect of sulforaphane (SFN), a natural NRF2 activator found in broccoli, on MM cell-induced osteoclast differentiation.</p><p><strong>Methods: </strong>Conditional medium (CM) derived from MM cells was used to induce osteoclast differentiation, and TRAP staining was performed to examine osteoclast. Gene expression was detected by western blotting or real-time PCR. Cell counting and EdU staining were performed to test macrophage proliferation.</p><p><strong>Results: </strong>We showed that the CM of MM cells downregulated the expression of ferroportin1 (Fpn1), the only known iron exporter in vertebrate cells, thereby increasing cellular iron levels in murine macrophage cells RAW264.7. Deferoxamine (DFO), an iron chelator, effectively blocked MM cell CM-induced osteoclast differentiation and macrophage proliferation, suggesting that iron overload played a key role in these cellular events. Subsequent mechanistic investigations revealed that MM cell CM induced osteoclast differentiation and macrophage proliferation by activating the JNK/AP-1/NFATC1 pathway and PI3K/AKT pathway. SFN was found to increase Fpn1 expression, leading to decreased cellular iron levels in RAW264.7 cells activated by MM cell CM. Importantly, the osteoclast differentiation and macrophage proliferation induced by MM cell CM were significantly inhibited by SFN.</p><p><strong>Conclusion: </strong>Altogether, our findings indicated that SFN inhibits MM cell-induced osteoclast differentiation and macrophage proliferation by elevating FPN1 levels. SFN could be a promising therapeutic strategy for MM-associated osteolysis.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"3"},"PeriodicalIF":2.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805874","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":"Influence of DPYD gene polymorphisms on 5-Fluorouracil toxicities in Thai colorectal cancer patients.","authors":"Chalirmporn Atasilp, Natchaya Vanwong, Pavitchaya Yodwongjane, Phichai Chansriwong, Ekaphop Sirachainan, Thanyanan Reungwetwattana, Pimonpan Jinda, Somthawin Aiempradit, Suwannee Sirilerttrakul, Monpat Chamnanphon, Apichaya Puangpetch, Nipaporn Sankuntaw, Patompong Satapornpong, Thomas Fabienne, Chonlaphat Sukasem","doi":"10.1007/s00280-024-04722-z","DOIUrl":"10.1007/s00280-024-04722-z","url":null,"abstract":"<p><p>DPYD polymorphisms have been widely found to be related to 5-FU-induced toxicities. The aim of this study was to establish significant associations between five single-nucleotide polymorphisms of DPYD and 5-FU hematological toxicities in Thai colorectal cancer patients. The toxicities were analyzed at the first and second cycles of 5-FU administration in 75 patients. Genotyping was performed using TaqMan real-time PCR. The genotype frequencies of DPYD*2A,1905 + 1 G > A and DPYD 1774 C > T were all wild type. The frequencies of genetic testing for DPYD*5, 1627 A > G, DPYD 1896T > C, and DPYD*9A, 85 A > G were 37.30% (AG; 34.60%, GG; 2.70%), 32.00% (TC; 25.30%, CC; 6.70%), and 13.40% (AG; 10.70%, GG; 2.70%), respectively. The results reveal significant findings with neutropenia occurring in 100% (2/2) of the patients with homozygous variant DPYD*9A (GG) from the first cycle of treatment for both Grade 1-4 and Grade 3-4 toxicities (P = 0.003 and P < 0.001 respectively). DPYD *9A was related to Grade 1-4 leukopenia (P = 0.001) and both Grade 1-4 and severe thrombocytopenia (P < 0.001 and P < 0.001) in the first cycle. In the second cycle, DPYD*5 was shown to be closely associated with no Grade 1-4 toxicity (P = 0.02). However, we found that 100% (2/2) of patients carrying the homozygous variant (GG) DPYD*5, presented no significant toxicity, so, DPYD*5 may be a predictive marker of neutropenia in patients treated with 5-FU. These outcomes suggest that there may be an increased risk of developing 5-FU-induced neutropenia in patients carrying the DPYD*9A, which should be considered as part of the standard procedure.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"2"},"PeriodicalIF":2.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799502","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 analysis of crushed venetoclax tablets combined with azacitizine for recurrent pediatric acute myeloid leukemia (AML).","authors":"Motohiro Matsui, Takeo Yasu, Atsushi Makimoto, Yuki Yuza","doi":"10.1007/s00280-024-04730-z","DOIUrl":"10.1007/s00280-024-04730-z","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of a combination therapy consisting of venetoclax (VEN) and azacytidine (AZA) for newly diagnosed acute myeloid leukemia (AML) has been confirmed in elderly patients. However, the clinical data on VEN for pediatric AML are limited. A combination therapy consisting of crushed VEN tablets and AZA (VEN/AZA) was administered to two children with recurrent AML. The pharmacokinetics of VEN were then analysed.</p><p><strong>Case presentation: </strong>[Patient 1] A 1-year-old, male patient who experienced an AML relapse following an allogeneic hematopoietic stem cell transplantation received three courses of VEN/AZA. At the initial dosage of VEN (8 mg/kg), the minimum plasma concentration (C_min) was only 0.44 µg/ml, which was far less than the optimal C_min of 1.2 µg/ml. Subsequent dose-escalation to 10 mg/kg only achieved C_min 0.42 µg/ml. [Patient 2] A 3-year-old, female patient in whom infantile acute lymphoblastic leukemia was originally diagnosed experienced a recurrence in the form of AML after lineage-switching. Three courses of VEN/AZA were administered with the same therapeutic drug monitoring as in Case 1. The C_min of VEN was 0.15 µg/ml at 8 mg/kg. Afterwards, voriconazole 16 mg/kg/day was begun for a concomitant fungal infection together with VEN 2 mg/kg. This combination finally achieved C_min 1.14 µg/ml probably through CYP3A4 inhibition by voriconazole. In terms of safety, only grade 4 hematological adverse events were observed in both patients. In terms of efficacy, patient 1 and patient 2 achieved stable disease status for two months and six months, respectively.</p><p><strong>Conclusion: </strong>Pediatric patients may scarcely achieve effective plasma concentration of VEN when crushed tablets are used at the same dosage as in adults.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"1"},"PeriodicalIF":2.7,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791109","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 comparison of the renal function biomarkers serum creatinine, pro-enkephalin and cystatin C to predict clearance of pemetrexed.","authors":"N de Rouw, R Beunders, O Hartmann, J Schulte, R J Boosman, H J Derijks, D M Burger, M M van den Heuvel, L B Hilbrands, P Pickkers, R Ter Heine","doi":"10.1007/s00280-024-04717-w","DOIUrl":"10.1007/s00280-024-04717-w","url":null,"abstract":"<p><strong>Introduction: </strong>For drugs with a narrow therapeutic window, there is a delicate balance between efficacy and toxicity, thus it is pivotal to administer the right dose from the first administration onwards. Exposure of pemetrexed, a cytotoxic drug used in lung cancer treatment, is dictated by kidney function. To facilitate optimized dosing of pemetrexed, accurate prediction of drug clearance is pivotal. Therefore, the aim of this study was to investigate the performance of the kidney function biomarkers serum creatinine, cystatin C and pro-enkephalin in terms of predicting the elimination of pemetrexed.</p><p><strong>Methods: </strong>We performed a population pharmacokinetic analysis using a dataset from two clinical trials containing pharmacokinetic data of pemetrexed and measurements of all three biomarkers. A three-compartment model without covariates was fitted to the data and the obtained individual empirical Bayes estimates for pemetrexed clearance were considered the \"true\" values (Cl_true). Subsequently, the following algorithms were tested as covariates for pemetrexed clearance: the Chronic Kidney Disease Epidemiology Collaboration equation using creatinine (CKD-EPI_CR), cystatin C (CKD-EPI_CYS), a combination of both (CKD-EPI_CR-CYS), pro-enkephalin as an absolute value or in a combined algorithm with age and serum creatinine, and lastly, a combination of pro-enkephalin with cystatin C.</p><p><strong>Results: </strong>The dataset consisted of 66 subjects with paired observations for all three kidney function biomarkers. Inclusion of CKD-EPI_CR-CYS as a covariate on pemetrexed clearance resulted in the best model fit, with the largest decrease in objective function (p < 0.00001) and explaining 35% of the total inter-individual variability in clearance. The predictive performance of the model to containing CKD-EPI_CR-CYS to predict pemetrexed clearance was good with a normalized root mean squared error and mean prediction error of 19.9% and 1.2%, respectively.</p><p><strong>Conclusions: </strong>In conclusion, this study showed that the combined CKD-EPI_CR-CYS performs best in terms predicting pharmacokinetics of pemetrexed. Despite the hypothesized disadvantages, creatinine remains to be a suitable and readily available marker to predict pemetrexed clearance in clinical practice.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":" ","pages":"799-806"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371051","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":"Successful desensitization in a patient with metastatic colorectal cancer presenting with regorafenib-mediated fix drug eruption.","authors":"Hazal Kayikci, C Tuccar, E Damadoglu, G Karakaya, A F Kalyoncu","doi":"10.1007/s00280-024-04719-8","DOIUrl":"10.1007/s00280-024-04719-8","url":null,"abstract":"<p><strong>Introduction: </strong>Regorafenib is an oral protein kinase inhinitor approved fot the treatment of metastatic colorecral cancer. We present a first successful case of desensitization in regorafenib-related fix-drug eruption in the literature.</p><p><strong>Case report: </strong>A 44-year-old female patient was diagnosed with metastatic colorectal adenocarcinoma. The patient received regorafenib treatment for malignancy recurrence. The patient was admitted to adult allergy clinic with developing recurrent fix drug eruption in the second cycle, on the 10th day of regorafenib treatment. The patient was given the third cycle of regorafenib treatment with a 6-day desensitization protocol, the first day of which consisted of 6 steps and and the third cycle was successfully completed.</p><p><strong>Management and outcome: </strong>Regorafenib-mediated delayed hypersensitivity reactions occur less frequently and and regorafenib hypersensitivity reactions are difficult to manage and experience is limited. This is the first successful desensitization protocol developed by us for regorafenib-related fix drug eruption and more cases are needed to be reported to confirm the desensitization protocol.</p><p><strong>Discussion: </strong>There is only one successful regorafenib desensitization protocol for severe delayed hypersensivity reaction in the literature, but there is no protocol developed for mild type delayed hypersensivity reaction. The management of fix-drug eruption primarily involves discontinuation and avoidance of the offending drug but our patient had a mild delayed-type reaction and there was no alternative to regarofenib treatment. We developed the rapid 6-step desensitization protocol (Day 1). According to this protocol, the patient was able to continue regorafenib treatment successfully.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":" ","pages":"815-818"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458679","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":"Phase I-II study of OBI-888, a humanized monoclonal IgG1 antibody against the tumor-associated carbohydrate antigen Globo H, in patients with advanced solid tumors.","authors":"Apostolia Maria Tsimberidou, Axel Grothey, Darren Sigal, Heinz-Josef Lenz, Howard S Hochster, Yee Chao, Li-Yuan Bai, Chia-Jui L Yen, Dong Xu, M Wayne Saville","doi":"10.1007/s00280-024-04714-z","DOIUrl":"10.1007/s00280-024-04714-z","url":null,"abstract":"<p><strong>Purpose: </strong>OBI-888 is a humanized, monoclonal IgG1 antibody specific to the tumor-associated carbohydrate antigen Globo H. We conducted a phase I-II study of OBI-888 in patients with advanced cancer.</p><p><strong>Methods: </strong>Patients were treated with OBI-888 5, 10, or 20 mg/kg IV weekly in Part A (\"3 + 3\" design) and 20 mg/kg IV weekly in Part B (Simon's 2-stage design) (1 cycle = 28 days).</p><p><strong>Results: </strong>Overall, 54 patients were treated (Part A, n = 14; Part B, n = 40). OBI-888 was safe and well tolerated across the doses studied, with a low incidence of OBI-888-related treatment emergent adverse events. The maximum tolerated dose of OBI-888 was not reached. No dose-limiting toxicities were noted up to the 20 mg/kg dose level (recommended phase 2 dose). Stable disease (SD) was noted in 28.6% and 20% of Parts A and B, respectively, including three patients with SD for 6+, 7+, and 9 months. Antibody-dependent cellular cytotoxicity (ADCC) was induced after each OBI-888 treatment (average increase, 3.8-fold and 4.7-fold in Parts A and B, respectively), suggesting that ADCC induction is a potential mechanism of action of OBI-888.</p><p><strong>Conclusions: </strong>OBI-888 was well tolerated. Prolonged SD was noted in three patients. ADCC was induced after each OBI-888 treatment.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":" ","pages":"787-798"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280630","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}