No significant differences were found in the incidence or severity of adverse events between the TACE+DP and TACE+D groups (any grade: 92.9% vs. 94.6%, P=0.270; grade 3 or 4: 33.8% vs. 37.3%, P=0.253). With favorable safety and tolerability, TACE combined with donafenib and PD-1 inhibitors significantly improved PFS, OS, and ORR compared to TACE combined with donafenib.
Clinical Trial Registration Number NCT05253053 Sponsored by No funding sources reported Background: Programmed Cell Death Ligand 1 (PD-L1) inhibitor durvalumab in combination with gemcitabine and cisplatin has been approved as first-line therapy for BTC...Another pt with prior immunotherapy (sintilimab), target therapy (donafenib) and chemotherapy had a tumor reduction of 39.1% (tinengotinib 10 mg QD plus atezo)... Tinengotinib in combination with atezo was well-tolerated for the treatment of Chinese BTC pts. Preliminary encouraging efficacy of tinengotinib in combination with atezo was observed in pts with heavily pre-treated BTC. The ongoing study is to further evaluate the safety and efficacy of tinengotinib in combination with atezo in pts with BTC who had prior immunotherapy and/or chemotherapy.
The combination of SCD1 inhibitor aramchol and deuterated sorafenib derivative donafenib displays promising anti-tumor effects in p53-wild type HCC patient-derived organoids and xenografted tumors. This combination therapy has potential clinical benefits for the patients with advanced HCC who have wild-type p53 and high levels of URI/SCD1.
Systemic treatment with molecularly targeted drugs and immune checkpoint inhibitors, such as sorafenib, lenflutinib, donafenib, atezolizumab plus bevacizumab, sintilimab plus IBI305, regorafenib, pembrolizumab and anti-Cytotoxic T Lymphocyte antigen 4 (CTLA-4) was recommended by guidelines, but with limited effectiveness for HCC patients with PVTT. In recent years, the comprehensive treatment of HCC has advanced greatly. This review aims to provide an insight into the treatment modalities available for HCC patients with PVTT.
A chromosome conformation capture assay confirmed that the increased expression of HMOX1 is caused by the significantly enhanced interaction between the promoter and upstream enhancer under dual-drug combination. Taken together, this study elucidates a new synergistic lethal interaction in liver cancer.
Donafenib was well-tolerated, and demonstrated clinical benefit in terms of improved PFS, ORR and DCRin patients with RAIR-DTC. The results suggest that donafenib could be a new treatment option for RAIR-DTC patients.
GEMOX combined with donafenib plus tislelizumab as the first-line therapy for unresectable BTC showed manageable toxicity and encouraging efficacy especially in terms of promising conversion rate in Stage III patients.
Lenvatinib was generally cost-effective in most studies, but not compared to donafenib or sorafenib (if the price sorafenib was significantly discounted).
In hepatocellular carcinoma treatment, sorafenib, oxaliplatin, 5-fluorouracil, capecitabine, lenvatinib, and donafenib are first-line drugs; regorafenib, apatinib, and cabozantinib are second-line drugs; and oxycodone, morphine, and fentanyl are commonly used analgesics...The precision and accuracy of all analytes were < 7.21% and 5.62%, respectively. Our study provides empirical support for a simple, reliable, specific, and suitable technique for clinical TDM and pharmacokinetics.
Both donafenib and lenvatinib can effectively treat patients with middle and advanced hepatocellular carcinoma, and the local control rate of donafenib is higher than that of lenvatinib. The treatment of intermediate--advanced hepatocellular carcinoma patients with donafinib has better clinical efficacy than levatinib, which can effectively reduce the severity of patients' disease and prolong their survival time.
Donafenib (DONA), a deuterium derivative of sorafenib, is used for advanced hepatocellular carcinoma (HCC). Increased exposure to these drugs may be due to their metabolism inhibition mediated by Ugt1a7. These pharmacokinetic interactions observed in this study may be of clinical significance, which may help adjust dose properly and avoid toxicity effects in patients with HCC and T2DM.
12 months ago
PK/PD data • Preclinical • Journal
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UGT1A9 (UDP Glucuronosyltransferase Family 1 Member A9) • UGT1A7 (UDP Glucuronosyltransferase Family 1 Member A7)
The combination of ZG005 with chemotherapeutic-reagents, cisplatin and donafenib, enhanced their anti-tumor efficacies. PK/TK analyses indicate a prolonged ZG005 receptor occupancy over 80%, consistent with in vitro binding results that are attribute to the S228P mutation in the IgG4 hinge region to prevent Fab exchange and enhance stability. The IND application of ZG005 has been approved by both FDA and NMPA, and the molecule is currently in phase I clinical trials for advanced solid tumors at escalated dosing of 0.3~20 mg/kg, Q3W, via i.v. administration.
Atezolizumab plus bevacizumab reduced the risk of death compared to placebo (HR 0·40; 95% CI 0·28-0·57), sorafenib (HR 0·58; 95% CI 0·42-0·80), lenvatinib (HR 0·63; 95% CI 0·44-0·89), atezolizumab plus cabozantinib (HR 0·64; 95% CI 0·43-0·97), nivolumab (HR 0·68; 95% CI 0·48-0·98) and donafenib (HR 0·69; 95% CI 0·48-0·99). Atezolizumab plus bevacizumab was not statistically superior to durvalumab plus tremelimumab (HR 0·74; 95% CI 0·52-1·06) and sintilimab plus IBI305 (HR 1·02; 95% CI 0·67-1·55) in reducing the risk of death. Efficacy was associated with a higher risk of grade 3 adverse events.
The LE group was treated with the emulsion of 0.5 mL lipiodol and 4 mg epirubicin. The combination of TAE and angiogenesis inhibitor donafenib resulted in a potentiated tumoricidal effect, anti-angiogenesis and antitumour T cell response in rabbit VX2 liver tumor model. This may provide a potential basis for exploring the immune-related mechanisms of embolization in liver cancer.