Combination Of 5-fluorouracil Research Articles

Phase II study of neoadjuvant chemotherapy with fluorouracil, leucovorin, oxaliplatin and docetaxel for resectable esophageal squamous cell carcinoma.

418 Background: Based on the JCOG1109 trial, neoadjuvant docetaxel, cisplatin, and fluorouracil (DCF) followed by surgery has become the standard of care for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Although the combination of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) demonstrated benefits for esophageal adenocarcinoma as a perioperative therapy, its safety and efficacy for locally advanced ESCC have not been evaluated. Methods: We conducted a multicenter phase II study of neoadjuvant FLOT therapy for ESCC. Patients with cT1N1-3M0-1 or cT2-3N0-3M0-1 (only supraclavicular lymph node (SCLN) metastasis is included as M1) based on the 8th edition of the UICC TNM staging system were eligible. Neoadjuvant chemotherapy consisted of oxaliplatin (85 mg/m 2 ), docetaxel (50 mg/m 2 ), and l-leucovorin (200 mg/m 2 ) on day 1, and continuous infusion of fluorouracil (2600 mg/m 2 /day) for 24 hours. This regimen was repeated every 2 weeks with a maximum of four cycles. The prophylactic antibody and G-SCF were not used mandatory. After completion of neoadjuvant chemotherapy, esophagectomy with extended lymphadenectomy was performed. Adjuvant treatment was prohibited for all patients. The primary endpoint was the pathological response rate (pRR), defined as the Grade 2 (more than two-thirds of the tumor is necrotic or fibrotic) or 3 (no viable tumor cells), based on the Japanese Classification of Esophageal Cancer. The sample size was determined based on an expected pRR of 38%, aiming for the lower bound of the 95% confidence interval to exceed the predetermined threshold of 20%. The expected number of patients to be enrolled was 60, with enrollment to be stopped when 45 patients with negative SCLN were enrolled. Results: Fifty-four patients were enrolled between September 2020 and January 2024. Patients with cStage I/II/III/IVB were 3/16/27/8. Of 54 patients, 45 patients were M0 without SCLN metastasis. Excluding 1 patient who did not receive any treatment after enrollment, 53 patients were included in the full analysis set. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (73.6%), and leukopenia (22.6%). Febrile neutropenia was observed in 1 patient (1.9%). Finally, 46 patients underwent surgery. No treatment-related deaths were observed and the incidence of operative morbidity was tolerable. The pRR was 43.4% (23/53) (95% CI 29.8-57.7, p=00002). This study met the primary endpoint. The radical resection rate was 83.0% (44/53). The pathological complete response rate was 13.2% (7/53). Conclusions: Neoadjuvant FLOT therapy showed a promising pathological response with acceptable toxicities. It was noteworthy that the incidence of febrile neutropenia was relatively lower with compared to neoadjuvant DCF therapy. This regimen might be a treatment option for locally advanced ESCC. Clinical trial information: jRCTs031200094.

Metabolomics insights into doxorubicin and 5-fluorouracil combination therapy in triple-negative breast cancer: a xenograft mouse model study.

Breast cancer is one of the most prevalent malignancies and a leading cause of death among women worldwide. Among its subtypes, triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive behavior and limited treatment options. This study aimed to investigate the effects of doxorubicin (DOX) and 5-fluorouracil (5-FU) as monotherapies and in combination using an established MDA-MB-231 xenograft model in female BALB/C nude mice employing advanced metabolomics analysis to identify molecular alterations induced by these treatments. We conducted comprehensive plasma and tumor tissue sample profiling using ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). Each treatment group exhibited unique metabolic profiles in plasma and tumor analysis. Univariate and enrichment analyses identified alterations in metabolic pathways. The combination treatment of DOX + 5-FU induced the most extensive metabolic alterations disrupting key pathways including purine, pyrimidine, beta-alanine, and sphingolipid metabolism. It significantly reduced critical metabolites such as guanine, xanthine, inosine, L-fucose, and sphinganine, demonstrating enhanced cytotoxic effects compared to individual treatments. The DOX treatment uniquely increased ornithine levels, while 5-FU altered sphingolipid metabolism, promoting apoptosis. This in vivo study highlights TNBC's metabolic alterations to chemotherapeutics, identifying potential biomarkers like L-fucose and beta-alanine, and provides insights for improving treatment strategies.

Phase II Study of Nanoliposomal Irinotecan (Nal-IRI) with 5-Fluorouracil and Leucovorin in Refractory Advanced High-Grade Neuroendocrine Cancer of Gastroenteropancreatic (GEP) or Unknown Origin.

Neuroendocrine carcinomas (NECs) are treated with a frontline platinum-etoposide combination with no standard second-line therapies. We explored a novel combination of nanoliposomal irinotecan (Nal-IRI), 5-fluorouracil (5-FU), and leucovorin (LV) in advanced refractory NECs and investigated the impact of UGT1A1*28 polymorphism on treatment outcomes and toxicity. We conducted an open-label, single-arm, multi-center Phase 2 trial in advanced NEC patients of gastroenteropancreatic (GEP) or unknown origin with progression or intolerance to first-line therapy. Eligible patients received nal-IRI 70 mg/m2 and leucovorin 400 mg/m2, followed by 5-FU 2400 mg/m2 biweekly till disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Next-generation sequencing (NGS) was performed on blood/tissue samples at baseline and during treatment. Eleven patients were enrolled, with nine evaluable for the primary endpoint. Seven were male, the median age was 66.7 years, and the median Ki-67 was 90%. We observed partial response in one patient, stable disease in six patients, and progressive disease in two patients. The median OS was 9.4 months (95% CI 2.9-29.3), and the median PFS was 4.4 months (95% CI 1.7-6.7). The most common adverse events were diarrhea (45%), nausea (45%), vomiting (45%), and fatigue (45%). The most common genetic mutations on NGS were TP53 (88.9%), CHEK2 (88.9%), and APC (33.3%). Patients with CHEK2 and APC mutation had longer PFS (p = 0.005 and p = 0.013, respectively). UGT1A1*28 polymorphism was not associated with OS, PFS, or toxicity. Nal-IRI with 5-FU/LV is a safe and effective treatment for refractory high-grade NECs of GEP or unknown origin. Future studies should explore novel combinations with Nal-IRI in high-grade NECs both in frontline and refractory settings.

Potential of Epigallocatechin-3-Gallate and 5-Fluorouracil Combination in Colorectal Cancer Therapy: Literature Review

Potential of Epigallocatechin-3-Gallate and 5-Fluorouracil Combination in Colorectal Cancer Therapy: Literature Review

Cedrus atlantica extract inhibits melanoma progression by suppressing epithelial-mesenchymal transition and inducing mitochondria-mediated apoptosis.

Melanoma has a low incidence, accounting for less than 5% of skin cancers; however, it is the most lethal cancer, primarily because of its high potential for metastasis and resistance to different treatments. Natural products can sensitize melanoma to chemotherapy and overcome drug resistance. Previous studies have reported Cedrus atlantica extract has various pharmacological benefits such as anti-inflammatory, antioxidant, antibacterial, and analgesic properties. This study aimed to explore the effects of C. atlantica extract (CAt) against melanoma in vitro and in vivo. The effects of CAt on B16F10 cell viability, proliferation, migration, invasion, and apoptosis were detected using MTT, colony formation, wound-healing, Boyden chamber, and TUNEL assays. Semi-quantitative RT-PCR and western blotting were used to measure mRNA and protein expression, respectively. Results revealed that CAt selectively decreased the viability of B16F10 cells and inhibited colony formation in a dose-dependent manner. CAt reduces cell migration and invasion by regulating epithelial-mesenchymal transition-associated proteins (Snail, E-cadherin, and vimentin). Moreover, CAt enhanced the Bax/Bcl-2 ratio and the expression of cleaved-caspase-9, caspase-3, and PARP1, resulting in the activation of mitochondria-mediated apoptosis. In an in vivo study, CAt significantly inhibited tumor growth and prolonged the lifespan of mice at a well-tolerated dose. Importantly, the combination of CAt and 5-fluorouracil (5-FU) exhibited synergistic growth suppression and attenuated the development of 5-FU resistance. Overall, the findings suggest that CAt holds promise as a potential drug or adjuvant to improve melanoma treatment.

EGFR-targeting polydopamine nanoparticles co-loaded with 5-fluorouracil, irinotecan, and leucovorin to potentially enhance metastatic colorectal cancer therapy

Despite all prevention programs, many cases of colorectal cancer (CRC) are diagnosed when they have already metastasized. Herein, chemotherapy is required, and combination of 5-fluorouracil, irinotecan, and leucovorin (FOLFIRI) is one of the first-line treatments chosen. However, it is so toxic that compromises patient outcomes. Thus, with the aim of improving FOLFIRI pharmacokinetics while reducing its side effects, the three compounds that make it up were simultaneously absorbed in this work into polydopamine nanoparticles (PDA NPs), also loaded with an antibody to target CRC cells overexpressing the epithermal growth factor receptor (EGFR). All adsorptions, which were successfully executed without toxic solvents, were electrostatic in nature according to the calorimetry results obtained. Otherwise, based on the experiments done, 5-flurouracil, irinotecan, and leucovorin release from PDA NPs followed a burst-like pattern, which was possibly mediated by Fickian diffusion mechanisms. Finally, the assays performed with two EGFR-overexpressing CRC cell lines showed that the uptake of the nanosystem was rapid, and that its therapeutic effect was very significant. It managed to greatly reduce the viability of these cells to 22–30% after 72 h of incubation. Furthermore, when tumor spheroids were developed and treated with PDA NPs loaded with FOLFIRI and the anti-EGFR antibody (FOLFIRI-CTX@PDA NPs), these demonstrated to continue to have very marked therapeutic activity. In addition, FOLFIRI-CTX@PDA NPs affected to a lesser extent the survival rate of stromal cells, with which viability experiments were also done. Therefore, the novel developed PDA nanocarrier could be a promising strategy to enhance metastatic CRC therapy hereafter.

Melanocortin-4 receptor antagonist TCMCB07 alleviates chemotherapy-induced anorexia and weight loss in rats.

Cancer patients undergoing chemotherapy often experience anorexia and weight loss that substantially deteriorates overall health, reduces treatment tolerance and quality of life, and worsens oncologic outcomes. There are currently few effective therapeutic options to mitigate these side effects. The central melanocortin system, which plays a pivotal role in regulating appetite and energy homeostasis, presents a logical target for treating anorexia and weight loss. In this preclinical study, we evaluated the efficacy of TCMCB07, a synthetic antagonist of the melanocortin-4 receptor, in mitigating anorexia and weight loss in several rat models of chemotherapy: cisplatin, 5-fluorouracil, cyclophosphamide, vincristine, doxorubicin, and a combination of irinotecan and 5-fluorouracil. Our results indicate that peripheral administration of TCMCB07 improved appetite, stabilized body weight, preserved fat and heart mass, and slightly protected lean mass after multiple cycles of chemotherapy. Furthermore, combining TCMCB07 with a growth differentiation factor 15 antibody enhanced treatment effectiveness. Similar effects from TCMCB07 treatment were observed in a rat tumor model following combination chemotherapy. No notable adverse effects nor increased chemotherapy-related toxicities were observed with TCMCB07 treatment. These findings suggest that peripheral administration of TCMCB07 holds promise as a therapeutic approach for alleviating chemotherapy-induced anorexia and weight loss, potentially benefiting numerous patients undergoing chemotherapy.

Comparison of Efficacy of Intralesional Triamcinolone and Combination of Triamcinolone With 5-Fluorouracil in The Treatment of Keloid

Objectives: To study the efficacy of intralesional Triamcinolone and combination of Triamcinolone with 5-Fluorouracil in the treatment of keloid in terms or reduction in height of lesion. Study Design: Cross-sectional analytical study. Place and Duration Of Study: Department of Plastic Surgery, Combined Military Hospital, Rawalpindi, Jul 2020 to Mar 2021. Methodology: A total of 56 patients suffering from keloid formation were included in our study. Patients who had received previous treatment for keloids were excluded. All patients were assessed for volume of keloid before and after 8 weeks of intervention. Group A patients received therapy with intralesional Triamcinolone 4 mg with 5-Fluorouracil 45 mg once weekly while Group B patients received intralesional Triamcinolone 10 mg alone once weekly. Patients were followed up after 8 weeks to ascertain mean reduction in volume of keloid post-intervention. Data was analyzed by SPSS 26.0. Results: The difference in total volume post-treatment between the two groups was significant, (p=0.001), however the difference in total volume reduction across both groups with treatment was not significant, (p=0.382). Treatment was effective in 23(82.1%) of with the combination of Triamcinolone and 5-Fluorouracil, while this figure was only 16(57.1%) with Triamcinolone alone, (p=0.042). Conclusion: The combination of intralesional Triamcinolone and 5-Fluorouracil is superior to intralesional Triamcinolone alone in the treatment of keloids, and may be considered for therapy in patients who do not respond to treatment with single agents.

Real-world outcomes of FOLFOXIRI plus bevacizumab in patients with metastatic colorectal cancer: the JSCCR-TRIPON study.

FOLFOXIRI plus bevacizumab is a standard first-line chemotherapy for patients with metastatic colorectal cancer (mCRC). However, due to the severe toxicities, this regimen is not widely used. There is limited data on the real-world efficacy and safety. We conducted a retrospective analysis of clinical data from mCRC patients who received FOLFOXIRI plus bevacizumab as first-line chemotherapy at 31 institutions. The initial dose was standardized according to the TRIBE regimen. Induction therapy was defined as a combination of oxaliplatin, irinotecan, and fluorouracil. Out of 104 patients who met the criteria, the median age was 58years (range, 16-72). 81% of patients had an eastern cooperative oncology group performance status (PS) of 0. An initial dose reduction was observed in 63% of patients. The median number of preplanned induction therapy cycles was 12 (range, 4-12). The completion of scheduled induction therapy cycles was observed in 45% of patients, with treatment-related toxicities being the main reason for discontinuation (63%). The median progression-free survival and overall survival were 12.8months (95% CI, 10.6-15.0) and 27.9months (95% CI 21.6-34.2), respectively. The objective response rate and disease control rate were 63.7% and 98.9%, respectively. The R0 resection rate was 21.2%. The main grade 3 or higher toxicities were neutropenia (51%), febrile neutropenia (10%), and nausea/vomiting (5%). No treatment-related deaths were observed. In a real-world clinical setting, FOLFOXIRI plus bevacizumab demonstrated efficacy and safety comparable to previous clinical trials.

Establishment of patient-derived organoids and a characterization based drug discovery platform for treatment of gastric cancer

BackgroundGastric cancer (GC) encompasses many different histological and molecular subtypes. It is a major driver of cancer mortality because of poor survival and limited treatment options. Personalised medicine in the form of patient-derived organoids (PDOs) represents a promising approach for improving therapeutic outcomes. The goal of this study was to overcome the limitations of current models by ameliorating organoid cultivation.MethodsOrganoids derived from cancer tissue were evaluated by haematoxylin and eosin staining, immunohistochemistry, mRNA, and whole-exome sequencing. Three representative chemotherapy drugs, 5-fluorouracil, docetaxel, and oxaliplatin, were compared for their efficacy against different subtypes of gastric organoids by ATP assay and apoptosis staining. In addition, drug sensitivity screening results from two publicly available databases, the Genomics of Drug Sensitivity in Cancer and Cancer Cell Line Encyclopaedia, were pooled and applied to organoid lines. Once key targeting genes were confirmed, chemotherapy was used in combination with poly (ADP ribose) polymerase (PARP)-targeted therapy.ResultsWe successfully constructed GC PDOs surgically resected from GC patient tissue. PDOs closely reflected the histopathological and genomic features of the corresponding primary tumours. Whole-exosome sequencing and mRNA analysis revealed that changes to the original tumour genome were maintained during long-term culture. The drugs caused divergent responses in intestinal, poorly differentiated intestinal, and diffuse gastric cancer organoids, which were confirmed in organoid lines. Poorly differentiated intestinal GC patients benefited from a combination of 5-fluorouracil and veliparib.ConclusionThe present study demonstrates that combining chemotherapy with PARP targeting may improve the treatment of chemotherapy-resistant tumours.

Prognostic impact of shift to low visceral fat mass after neoadjuvant chemotherapy in patients with esophageal cancer.

Based on the JCOG1109 trial, it is suggested that the combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) could potentially become a standard neoadjuvant chemotherapy regimen, alongside the conventional 5-fluorouracil and cisplatin (CF) therapy, for esophageal cancer. However, there are few reports on the impact of body composition changes associated with neoadjuvant chemotherapy on prognosis. Our study aimed to explore the effect of different neoadjuvant chemotherapy regimens on body composition during treatment and the impacts of body composition changes on their prognosis. This is a retrospective study of 215 patients with advanced thoracic esophageal cancer who had surgery after neoadjuvant chemotherapy from 2013 to 2019. Computed tomography scans were performed before and after neoadjuvant chemotherapy to assess body composition. Skeletal muscle mass index (SMI) was calculated by dividing total skeletal muscle mass at the 3rd lumbar level by the square of height, while visceral and subcutaneous fat masses were measured at the level of umbilicus. Patients in the lowest 25% of both sexes were classified into the low visceral fat and low subcutaneous fat groups, respectively. Of the patients enrolled, 178 were male and 37 were female. Among them, 91 had clinical Stage II disease, and 124 had clinical Stage III disease. Additionally, 146 patients received neoadjuvant chemotherapy CF, and 69 received neoadjuvant chemotherapy DCF. Comparing the DCF and CF groups, the DCF group consisted of significantly younger patients (p < .01), a higher proportion of males (p = .03), and a greater number of clinical Stage III cases (p < .01). However, although percent change in SMI and visceral fat mass was not significantly different between two regimens, percent change in subcutaneous fat mass was significant in the DCF group. The major prognostic factors for patients undergoing surgery after neoadjuvant chemotherapy for thoracic esophageal cancer were clinical Stage III, transition to low visceral fat, and response rating (SD/PD), while the specific neoadjuvant chemotherapy regimen did not significantly influence the outcomes. This study suggests that prevention of the shift to low visceral fat throughout the neoadjuvant chemotherapy process should improve patient outcomes.

Clinical outcomes of second-line chemotherapy in patients with advanced pancreatic adenocarcinoma: a real-world study.

Little progress has been made in recent years using first-line chemotherapy, including gemcitabine combined with nab-paclitaxel, FOLFIRINOX, and NALIRIFOX, for advanced pancreatic adenocarcinoma (APC). In addition, the optimal second-line chemotherapy regimen has not been determined. This study aimed to compare the effectiveness of different types of second-line chemotherapy for APC. Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective analysis. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil- and gemcitabine-based chemotherapy as first-line treatment, respectively. Demographic and clinical features, except age and liver metastasis, were comparable between the two groups (P < 0.05). The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil- and gemcitabine-based combined regimen for first-line therapy, respectively (HR = 1.244, 95% CI = 1.090-1.419; P < 0.001). The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care, respectively (HR = 0.766, 95% CI = 0.677-0.867; P < 0.001). The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination therapy. A 5-fluorouracil- or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC.

Characterization and optimization of colon specific nanosponges immobilized polymeric microbeads formulation for the combined delivery of 5-fluorouracil and curcumin

Introductionand purpose: Site-specific delivery systems are highly advantageous for local cancer treatment as they allow a more significant delivery of the drug to the tumor with minimal systemic side effects. Furthermore, combination therapy is a promising approach that attracts more attention in cancer treatment due to its synergistic effects. In this work, nanosponges immobilized polymeric microbeads for colon-specific delivery systems were developed for a drug combination of 5-fluorouracil and curcumin to treat colorectal cancer. MethodsSodium alginate and low molecular chitosan polymers were used to create microbead-based formulations containing curcumin-encapsulated nanosponges and 5-fluorouracil. To improve curcumin's low solubility, Diphynylacarbonate (DPC) hyper cross-linking of β-CD was used to create curcumin-loaded β-CD nanosponges that further incorporated in the polymeric microbeads along with free 5-fluorouracil. ResultsThe optimized microbeads were spherical with a mean particle size of 1.1 ± 0.05 mm. The produced beads were subsequently coated with a multilayer coating of ethyl cellulose and Eudragit S100 polymers, which functioned as pH-dependent and time-dependent coatings to ensure drug delivery to the colon. The developed formulation (Coated MB5) showed controlled release of the drug and sustained cytotoxic effect. The release profiles of 5-fluorouracil and curcumin from Coated MB5 were best described by zero-order followed by first-order release functions. About 66.4 % of 5-FU and 73.1 % of curcumin were released for 24 h. In vivo roentgenographic evaluation in a rabbit model indicated that the optimized coated microbeads successfully reached the colon 7–9 h after administration. ConclusionsAs a prospective colon-specific drug delivery system, a successful formulation (Coated MB5) was developed for the combined delivery of 5-fluorouracil and curcumin. More in vivo studies are needed to demonstrate the therapeutic efficacy of optimized formulations and their potential to improve colorectal cancer therapy by providing a more targeted administration of combination medicines with fewer undesirable side effects.

Clinical outcomes of liposomal irinotecan in patients with advanced pancreatic cancer previously treated with conventional irinotecan: A meta-analysis of real-world evidence.

Pivotal clinical trials supported survival benefits of liposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin in patients with pancreatic ductal adenocarcinoma (PDAC) who previously received gemcitabine-based therapy. There are concerns about the benefits of nal-IRI in patients who received FOLFIRINOX (combined fluorouracil, leucovorin, IRI, and oxaliplatin) because of potential cross-resistance to IRI. The objective of this meta-analysis was to characterize the impact of the previous receipt of IRI on the outcomes of nal-IRI regimens in patients with advanced PDAC. Real-world studies evaluating the outcomes of nal-IRI in patients who had prior IRI exposure published up to April 2023 were searched using electronic databases. The meta-analysis was conducted using a random effects model to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Eight studies (n=1368 patients) were included. The pooled median progression-free survival (PFS) was 2.02 months (95% CI, 1.43-2.57 months), and the median overall survival (OS) was 4.26 months (95% CI, 3.03-5.39 months). Patients with prior IRI exposure had PFS (HR, 1.17; 95% CI, 0.94-1.47; p=.17) and OS (HR, 1.16; 95% CI, 0.95-1.42; p=.16) comparable to patients without prior IRI exposure. Likewise, patients who had progressive disease on conventional IRI had PFS (HR, 1.50; 95% CI, 0.73-3.08; p=.24) and OS (HR, 1.70; 95% CI, 0.68-4.27; p=.26) with nal-IRI comparable to patients who had no progressive disease. Prior IRI exposure does not affect the survival outcomes of nal-IRI regimens in patients who have advanced PDAC. The selection of later lines of chemotherapy regimens should be based on the differential safety profile, patient status, the cost of treatment, and health-related quality of life.

Daidzein nanosuspension combined with 5-fluorouracil induces apoptosis and alleviate inflammation in Caco-2 colorectal adenocarcinoma cells

Colorectal cancer is the third most common malignancy worldwide and the second most common cause of cancer deaths. Alternative treatment strategies, including nano-based formulations, show remarkable promise to improve the efficacy of chemotherapy. The soy isoflavone daidzein has attracted attention for its anti-cancer activity. The aim of this study was to investigate the effects of daidzein nanosuspension with 5-fluorouracil on apoptosis and inflammation induced in human colorectal adenocarcinoma cells (Caco-2). Cytotoxicity, total antioxidant/oxidant status (TAS, TOS), and the expression of proteins associated with apoptosis and inflammation were analyzed by the MTT, ELISA and qRT-PCR, respectively. Daidzein nanosuspension showed a strong cytotoxicity (IC50 = 240.3 μM for daidzein, IC50 = 35.34 μM for daidzein nanosuspension) compared to daidzein. The combination of 5-fluorouracil and daidzein nanosuspension treatment showed a synergistic antiproliferative effect without increasing oxidative stress. The combination showed a significant increase in p53 levels and a significant decrease in Bcl-2, IL-6, TNF-α and MMP-9 levels. qRT-PCR results showed that the combinations of daidzein and DZ-NS with 5-FU regulated these parameters in Caco-2 cells. In conclusion, daidzein nanosuspension with 5-fluorouracil treatment reduced the proliferation and inflammation and increased apoptosis of Caco-2 cells without oxidative stress. The current study shows that this combination also elucidates several signaling pathways, including effects on oxidative stress, apoptosis, and inflammation. The integration of this nanotechnology approach into traditional chemotherapy will form the basis of an innovative strategy.

Enhancing Prostate and Bladder Cancer Treatment: Exploring the Synergistic Potential of Entecavir and 5-Fluorouracil Combinations

Enhancing Prostate and Bladder Cancer Treatment: Exploring the Synergistic Potential of Entecavir and 5-Fluorouracil Combinations

The safety and efficacy of adebelimumab combined apatinib and hepatic artery infusion chemotherapy in the treatment of unresectable hepatocellular carcinoma: A retrospective study.

e16175 Background: The combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) used for hepatic arterial infusion chemotherapy (HAIC) has shown promise for advanced hepatocellular carcinoma (HCC) patients. The combined therapy of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) is now an approved first-line approach for unresectable HCC. This study evaluated the safety and the effect of combining Adebelimumab (a PD-L1 inhibitors) and Apatinib (a tyrosinase kinase inhibitor) with HAIC-FOLFOX for unresectable HCC patients. Methods: The records of patients with unresectable HCC treated with HAIC from March 2023 to November 2023 at our center were retrospectively reviewed. Eligible patients were given a maximum of four cycles of FOLFOX-HAIC, along with Adebelimumab and Apatinib, until either disease progression or intolerable toxicities emerged. The primary outcome measured was the safety and the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modify RECIST of combined therapy. Results: Twenty patients were enrolled in the study. The most frequent grade ≥3 or above treatment-related adverse events included elevation of AST (50%) and diminished PLT count (15%). There was no treatment related death. Based on RECIST v1.1 and mRECIST criteria, the confirmed ORR stood at 35% and 70%, with a disease control rate of 85% both. Conclusions: The combination of Adebelimumab, apatinib, and FOLFOX-HAIC demonstrated manageable safety and encouraging results for unresectable HCC.

Hepatic artery infusion of FOLFOX chemotherapy and camrelizumab combined with sorafenib for advanced stage hepatocellular carcinoma (Double-IA-001): A phase II trial.

e16199 Background: Hepatic arterial infusion chemotherapy (HAIC) using a combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown excellent local control for hepatocellular carcinoma (HCC) patients classified under Barcelona Clinic Liver Cancer (BCLC) stage C. In China, both camrelizumab (a PD-1 inhibitor) and sorafenib were approved first-line approach for advanced stage HCC. This study (ChiCTR2100041874) aimed to the efficacy of combined hepatic artery infusion of FOLFOX chemotherapy and camrelizumab, together with sorafenib in BCLC stage C. Methods: Eligible patients were given a maximum of six cycles of hepatic artery infusion of HAIC-FOLFOX and camrelizumab, along with sorafenib, until either disease progression, intolerable toxicities emerged or disease downstaged and converted to received surgical resection. The primary outcome measured was the objective response rate (ORR) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: Twenty-five patients were enrolled. Based on mRECIST criteria, by the end of Feb 4, 2024, the confirmed ORR stood at 44.0%, with a disease control rate of 60.0%. The median progression-free survival was 3.33 months. Patient quality of life had a transient deterioration within four cycles of treatment, and generally recovered thereafter. A total of 28.0% of patients had grade ≥3 or above treatment-related adverse events, which could be alleviated after symptomatic treatment. Conclusions: The combination of double intrahepatic infusion of FOLFOX and camrelizumab with sorafenib demonstrated encouraging results and manageable safety concerns for BCLC stage C HCC. Clinical trial information: ChiCTR2100041874.

CLARITY-PanTumor01: A phase 2 trial of the claudin 18.2-specific antibody-drug conjugate AZD0901 (CMG901) in patients with CLDN18.2-expressing advanced solid tumors.

TPS3163 Background: Gastric/gastroesophageal junction (G/GEJ) and pancreatic cancer are associated with poor outcomes and high unmet need. Claudin 18.2 (CLDN18.2) is highly expressed in gastric, esophageal, and pancreatic ductal adenocarcinoma (PDAC), and is a clinically validated target. AZD0901 is a potential first-in-class antibody-drug conjugate (ADC) comprising a humanized anti-CLDN18.2 IgG1 antibody conjugated via a protease-cleavable linker to monomethyl auristatin E (MMAE), a cytotoxic microtubule-disrupting agent. Interim results from the ongoing, first-in-human, Phase 1 trial of AZD0901 monotherapy in patients with G/GEJ cancer (NCT04805307) who were refractory to and/or intolerant of standard therapies demonstrated promising efficacy and a manageable safety profile. Here we describe an ongoing, Phase 2 study of AZD0901 in patients with CLDN18.2-expressing advanced solid tumors, including G/GEJ cancer and PDAC. Methods: This open-label, multicenter study (NCT06219941) comprises multiple substudies. Substudy 1 is recruiting patients with human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2-expressing G/GEJ cancer with ≤2 prior lines of therapy for unresectable or metastatic disease, who are randomized 1:1 to receive AZD0901 1.8 or 2.2 mg/kg intravenous (IV) every 3 weeks (Q3W). Substudy 2 is recruiting patients with previously untreated CLDN18.2-expressing metastatic PDAC to receive AZD0901 (up to 2.2 mg/kg IV Q3W) and either a combination of 5-fluorouracil 2400 mg/m2 IV on Days 1 and 2 Q2W, leucovorin 400 mg/m2 or l-leucovorin 200 mg/m2 IV on Days 1 and 2 Q2W, and irinotecan 150 or 180 mg/m2 or nanoliposomal irinotecan 50 mg/m2 IV on Day 1 Q2W (Arm 1), or gemcitabine 1000 mg/m2 IV on Days 1 and 8 Q3W (Arm 2), per investigator’s choice. Treatment continues until disease progression, unacceptable toxicity, or withdrawal of consent. Eligible patients are aged ≥18 years with histologically confirmed, unresectable or metastatic disease, ≥1 measurable lesion per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, and Eastern Cooperative Oncology Group performance status 0–1. Key exclusion criteria include unstable and/or active peptic ulcer disease or digestive tract bleeding, ascites requiring drainage, central nervous system metastases, and prior exposure to an MMAE-based ADC or CLDN-18.2-targeted agents other than an anti-CLDN18.2 targeted monoclonal antibody. Primary endpoints include safety, tolerability, and objective response rate per RECIST v1.1. Secondary endpoints include overall survival, progression-free survival, duration of response, disease control rate, best change in target lesion size, pharmacokinetics, immunogenicity, and pharmacodynamics. Recruitment began in December 2023, and sites across Australia, Asia, Europe, and North America will enroll patients. Clinical trial information: NCT06219941 .

Synergistic Therapy for Graves’ Ophthalmopathy-Associated Eyelid Retraction: Steroid, 5-FU, and Botulinum Neurotoxin a Combination

Background: Graves’ ophthalmopathy (GO) is characterized by upper eyelid retraction (UER), the most prevalent clinical sign. We aimed to assess the clinical efficacy of a multimodal combination of steroids, 5-fluorouracil (5-FU), and botulinum neurotoxin A (BoNT-A) injections in managing UER with GO and analyze the clinical factors in relation to the injection response. Methods: A total of 37 eyes from 23 patients were enrolled for UER with GO. At the endocrinology clinic, the patients were referred to the ophthalmology clinic after taking antithyroid medication for an average of 5.76 months (13 patients), while 10 patients were initially diagnosed with GO and referred to the endocrinology clinic for management of the thyroid hormone function. They performed an orbital computed tomography (CT) scan and measured the cross-sectional area of the orbit, orbital fat, and each extra ocular muscle (EOM) except for the inferior oblique muscle 4 mm behind the eyeball. Each of the EOMs and orbital fat were calculated as a ratio to the total orbit area. A total of 0.1 cc of triamcinolone (40 mg/mL), dexamethasone (5 mg/mL), 5-FU, and BoNT-A (2.5 units) was injected transconjunctivally. Medical records were examined and photographs were utilized to assess MRD1, inferior palpebral fissure (IPF), and lid lag during down gaze before and after the injection. The patients were divided into two groups: responders (more than 1 mm decrease in MRD1 after injection) and non-responders. During the follow-up period (11.0 ± 11.6 months), any potential adverse effects were monitored. Results: CAS decreased from 3.0 ± 0.8 to 1.4 ± 0.5 after the injection, and MRD1 decreased from 5.0 ± 0.9 mm to 4.5 ± 1.3 mm. Sixty percent of the patients were responders. Before and after the injection, the difference between IPF and MRD1 in responders was 0.60 ± 1.10 mm and 0.90 ± 0.90 mm, respectively, whereas, in non-responders, it was −0.57 ± 0.88 mm and −0.15 ± 0.75 mm, respectively. In the responders, pre-injection IPF and FT4 were significantly higher (p &lt; 0.05). Responders had a larger EOM cross-sectional area (153.5 ± 18.0 mm2), including a larger lateral rectus muscle cross-sectional area (37.6 ± 9.7 mm2) than non-responders (132.0 ± 27.9 mm2; 29.1 ± 8.1 mm2). In responders, the treatment effect on IPF and MRD1 remained consistent at 1.2 ± 3.4 mm and 1.2 ± 1.6 mm, respectively, during the latest follow-up assessment. Conclusions: The combination injection of corticosteroids, 5-FU, and BoNT-A would be effective, especially, in patients with hyperthyroidism and an elongated IPF. Additionally, an increase in EOM cross-sectional area on CT, up to 150 mm2, may serve as an additional positive indicator for the use of multimodal injections in UER with GO.