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1.
World J Gastroenterol ; 30(36): 4071-4077, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39351247

RESUMEN

BACKGROUND: Surgical resection and liver transplantation (LT) are the most effective curative options for hepatocellular carcinoma (HCC). However, few patients with huge HCC (> 10 cm in diameter), especially those with portal vein tumor thrombus (PVTT), can receive these treatments. Selective internal radiation therapy (SIRT) can be used as a conversion therapy for them because it has the dual benefit of shrinking tumors and increasing residual hepatic volume. However, in patients with huge HCC, high lung absorbed dose often prevents them from receiving SIRT. CASE SUMMARY: A 35-year-old man was admitted because of emaciation and pain in the hepatic region for about 1 month. The computed tomography scan showed a 20.2 cm × 19.8 cm tumor located in the right lobe-left medial lobes with right portal vein and right hepatic vein invasion. After the pathological type of HCC was confirmed by biopsy, two conversions were presented. The first one was drug-eluting bead transarterial chemoembolization plus hepatic arterial infusion chemotherapy and lenvatinib and sintilimab, converted to SIRT, and the second one was sequential SIRT with continued systemic treatment. The tumor size significantly decreased from 20.2 cm × 19.8 cm to 16.2 cm × 13.8 cm, then sequentially to 7.8 cm × 6.8 cm. In the meantime, the ratio of spared volume to total liver volume increased gradually from 34.4% to 55.7%, then to 62.9%. Furthermore, there was visualization of the portal vein, indicating regression of the tumor thrombus. Finally, owing to the new tumor in the left lateral lobe, the patient underwent LT instead of resection without major complications. CONCLUSION: Patients with inoperable huge HCC with PVTT could be converted to SIRT first and accept surgery sequentially.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Invasividad Neoplásica , Vena Porta , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/diagnóstico por imagen , Masculino , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Vena Porta/patología , Vena Porta/diagnóstico por imagen , Vena Porta/cirugía , Trasplante de Hígado/métodos , Adulto , Resultado del Tratamiento , Quimioembolización Terapéutica/métodos , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Tomografía Computarizada por Rayos X , Hígado/patología , Hígado/diagnóstico por imagen , Hígado/cirugía , Quinolinas
2.
Cancer Immunol Immunother ; 73(12): 249, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39358645

RESUMEN

BACKGROUND: Treatment options for advanced intrahepatic cholangiocarcinoma (ICC) are currently limited. Chemo-containing regimens are the mainstay treatments but associated with notable toxicity, poor tolerance, and reduced compliance, necessitating exploration of alternative therapies. Lenvatinib plus PD-1 inhibitors has shown substantial clinical activity in preliminary studies. This study aimed to assess the effectiveness and safety of lenvatinib plus toripalimab (a novel PD-1 antibody) as chemo-free therapy in advanced ICC. METHODS: This retrospective study included consecutive advanced ICC patients receiving lenvatinib plus toripalimab between February 2019 and December 2023. The main outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors and exploratory analyses for genetic alternations were also conducted. RESULTS: A total of 78 patients were included, with a median follow-up of 25.9 months. Median OS and PFS were 11.3 (95% CI: 9.5-13.1) and 5.4 (95% CI: 3.8-7.0) months, respectively. ORR was 19.2% and DCR was 75.6%. The incidence of grade 3 or 4 adverse events (AEs) was 50.0%, with no grade 5 AEs reported. Patients with normal baseline CA19-9 levels exhibited a higher ORR (p = 0.011), longer PFS (11.5 versus 4.6 months; HR 0.47; p=0.005), and OS (21.0 versus 9.7 months; HR 0.43; p=0.003). The presence of IDH1 mutations correlated with increased ORR (60.0% versus 8.9%, p=0.016). CONCLUSION: Lenvatinib plus toripalimab represents an effective and well-tolerated chemo-free therapeutic option for advanced ICC. Baseline CA19-9 levels and IDH1 mutations may serve as predictive treatment-related biomarkers.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de los Conductos Biliares , Biomarcadores de Tumor , Colangiocarcinoma , Compuestos de Fenilurea , Quinolinas , Humanos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/mortalidad , Masculino , Femenino , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Persona de Mediana Edad , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/administración & dosificación , Anciano , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/genética , Adulto , Pronóstico , Anciano de 80 o más Años
3.
Sci Rep ; 14(1): 23961, 2024 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-39397104

RESUMEN

This research was intended to compare the clinical efficacy of hepatic arterial infusion chemotherapy (HAIC) in conjunction with lenvatinib and PD1 inhibitors to first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma(ICC). The research enrolled advanced ICC patients who underwent HAIC plus lenvatinib and PD1 inhibitor(n = 51) or first-line systemic chemotherapy(cisplatin + gemcitabine, n = 39) between July 2020 to January 2023 in Zhongshan People's Hospital.Their clinical outcomes were assessed through measurement of parameters encompassing objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and treatment-related adverse events (TRAEs). In accordance with the RECIST1.1, the ORR in the HAIC + L + P and SC groups was 43.1% and 20.5%, while the DCR was 90.2% and 69.2%, respectively (P = 0.04 and = 0.02, respectively). The change in the maximum diameter of intrahepatic target lesions in patients before and after treatment and the diameter of intrahepatic tumors in the HAIC + L + P group were sharply smaller versus the SC group ( P < 0.001). The HAIC + L + P group had prolonged mOS (16.8 months vs. 11.0 months, P = 0.01) and mPFS (12.0 months vs. 6.9 months, P < 0.01) in comparison with the SC group. Compared to first-line systemic chemotherapy(cisplatin + gemcitabine), HAIC plus lenvatinib and PD-1 inhibitors contributes to improvement of tumor response and prolongation of OS and PFS in advanced ICC patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Colangiocarcinoma , Compuestos de Fenilurea , Quinolinas , Humanos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Masculino , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Femenino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Gemcitabina , Infusiones Intraarteriales , Adulto , Resultado del Tratamiento , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Supervivencia sin Progresión
4.
Medicina (Kaunas) ; 60(10)2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39459388

RESUMEN

Background/Objectives: Uterine sarcoma, a rare cancer originating in the smooth muscle of the uterus, exhibits high rates of recurrence and metastasis. It represents one of the most challenging types of cancer due to its chemorefractory nature, showing little response to conventional chemotherapy methods and displaying a relative survival rate of 30-40%. A potentially promising approach for treating uterine sarcoma involves combination therapy with paclitaxel (PAC), a microtubule-targeting agent, and seliciclib (SEL), a cyclin-dependent kinase inhibitor. SEL has been identified as a drug that can enhance the effectiveness of PAC through synergistic effects. To further refine this treatment strategy, an efficient analytical tool capable of simultaneously measuring the concentrations of PAC and SEL in blood plasma is needed. This tool would make it easier to study the pharmacokinetic interactions of potential drugs and assist in monitoring therapy when administering this combination treatment. Regrettably, a method meeting these specific requirements has not been documented in the existing literature. Methods: This article introduces the first HPLC technique employing a PDA detector to concurrently measure PAC and SEL levels in plasma. The methodology underwent validation in accordance with the ICH standards for validating bioanalytical methods. Results: The method exhibited linearity in the concentrations ranging from 0.8 to 100 µg mL-1 for both PAC and SEL. The limits of quantification were determined and found to be 1.34 and 1.25 µg mL-1 for PAC and SEL, respectively. All the other validation criteria conformed to the ICH validation standards. The HPLC-PDA method was successfully employed to quantify both PAC and SEL in plasma samples with a high level of reliability (in terms of accuracy and precision). The eco-friendliness of the approach was verified using three thorough assessments. This technique serves as a valuable asset in establishing the correct dosage and administration schedule for the combined treatment involving PAC and SEL, ensuring the desired therapeutic effects and safety in managing uterine sarcoma. Conclusions: The proposed HPLC-PDA method is the first reliable and eco-friendly method developed to simultaneously determine PAC and SEL in high-throughput plasma samples in clinical laboratories.


Asunto(s)
Paclitaxel , Sarcoma , Neoplasias Uterinas , Humanos , Paclitaxel/farmacocinética , Paclitaxel/uso terapéutico , Paclitaxel/sangre , Paclitaxel/administración & dosificación , Femenino , Sarcoma/tratamiento farmacológico , Sarcoma/sangre , Cromatografía Líquida de Alta Presión/métodos , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/sangre , Compuestos de Fenilurea/farmacocinética , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/sangre , Compuestos de Fenilurea/administración & dosificación , Reproducibilidad de los Resultados
5.
Sci Rep ; 14(1): 25616, 2024 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-39463401

RESUMEN

BACKGROUND: Recent studies have highlighted that TACE in conjunction with Lenvatinib (TACE-L) offers a promising adjunct therapy for advanced HCC patients, outperforming TACE plus Sorafenib (TACE-S). However, there has been a lack of research comparing these two regimens for intermediate HCC. AIMS: This study aims to address the research gap by evaluating the efficacy of TACE-L versus TACE-S in intermediate HCC patients. METHODS: A retrospective analysis was conducted on a cohort of consecutive intermediate HCC patients who received either TACE-L or TACE-S from November 2018 to December 2022. Portal vein width was assessed using abdominal NMRI or Doppler ultrasonography, and inflammatory markers were derived from routine blood counts. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse drug reactions (ADRs). RESULTS: The study included 117 patients, with 56 in the TACE-S group and 61 in the TACE-L group. The TACE-S group demonstrated superior OS (HR = 1.704, 95% CI: 1.012-2.870, p = 0.045) compared to the TACE-L group. No significant difference was observed in PFS (HR:1.512, 95% CI: 0.988-2.313, p = 0.057) between the two groups. Subgroup analyses revealed that male patients, those with cirrhosis, and those with more than four tumors had better OS and PFS in the TACE-S group than in the TACE-L group. Inflammatory markers were comparable between the groups. The TACE-S group experienced a higher incidence of palmar-plantar erythrodysesthesia syndrome (PPE) (14/56 [25%] vs. 5/61 [8.1%], p = 0.014) but a lower incidence of hypertension (3/56 [5.3%] vs. 11/61 [18%], p = 0.035) compared to the TACE-L group. CONCLUSIONS: In patients with intermediate HCC, TACE-S was found to be more effective in terms of OS than TACE-L. No significant disparity was noted in PFS between the two treatment groups.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Sorafenib , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Quimioembolización Terapéutica/métodos , Quimioembolización Terapéutica/efectos adversos , Masculino , Sorafenib/uso terapéutico , Sorafenib/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Femenino , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Resultado del Tratamiento , Terapia Combinada , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación
6.
Front Immunol ; 15: 1449663, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39411718

RESUMEN

Objective: Comparing the efficacy of transarterial chemoembolization (TACE) combined with lenvatinib plus tislelizumab (TLT) with TACE combined with lenvatinib (TL) for unresectable hepatocellular carcinoma, particularly in determining which patients can benefit more from the TLT treatment. Methods: From March 2021 to September 2023, a total of 169 patients from three centers were included in this study, with 103 patients receiving TLT and 66 patients receiving TL. The Kaplan-Meier method was utilized to evaluate the cumulative overall survival (OS) and progression-free survival (PFS) between the two groups and were assessed using the log-rank test. Subgroup analysis on tumor number, maximum tumor diameter, presence of portal vein thrombosis, AFP level, and Child-Pugh class were conducted. Results: The median OS was 26 months in the TLT group, and 20 months in the TL group. The median PFS was 14 months in the TLT group and 9 months in the TL group. The Kaplan-Meier curve demonstrated a significantly superior OS and PFS in the TLT group compared to the TL group. Subgroup analysis showed that for patients with a maximum tumor diameter greater than 7 cm, AFP > 400 ng/ml and accompanied by portal vein tumor thrombus, and Child-Pugh class A, there was a statistically significant difference in OS between TLT and TL groups. Conclusions: OS and PFS were significantly improved in patients who received TLT compared to those who received TL, patients with a largest tumor diameter greater than 7 cm, AFP > 400 ng/ml, Child-Pugh class A and PVTT appeared to derive more benefit.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Persona de Mediana Edad , Quimioembolización Terapéutica/métodos , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Resultado del Tratamiento , Estudios de Cohortes , Estudios Retrospectivos
7.
Cancer Immunol Immunother ; 73(12): 240, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39358463

RESUMEN

BACKGROUND: Lenvatinib, programmed cell death 1 (PD-1) antibodies, and gemcitabine and oxaliplatin (GEMOX) chemotherapy have shown significant antitumor activity as first-line therapy against biliary tract cancer. This study evaluated their efficacy and safety as non-first-line therapy in advanced gallbladder cancer (GBC). METHODS: Patients with advanced GBC who received lenvatinib combined with anti-PD-1 antibodies and GEMOX chemotherapy as a non-first-line therapy were retrospectively analyzed. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR) and safety. RESULTS: A total of 36 patients with advanced GBC were included in this study. The median follow-up time was 11.53 (95% confidence interval (CI): 2.2-20.9) months, and the ORR was 36.1%. The median OS and PFS were 15.1 (95% CI: 3.2-26.9) and 6.1 (95% CI: 4.9-7.2) months, respectively. The disease control rate (DCR) and clinical benefit rate (CBR) were 75% and 61.1%, respectively. Subgroup analysis demonstrated that patients with programmed cell death-ligand 1 (PD-L1) expression had significantly longer PFS and OS than those without PD-L1 expression. Additionally, patients with a neutrophil-lymphocyte ratio (NLR) < 5.57 had a longer OS than those with an NLR ≥ 5.57. All patients experienced adverse events (AEs), with 61.1% experiencing grade 3 or 4 AEs, including myelosuppression (13.9%) and fatigue (13.3%), alanine transaminase or aspartate transaminase levels (8.3%), and diarrhea (8.3%). No grade 5 AEs were reported. CONCLUSION: Anti-PD-1 antibodies combined with lenvatinib and GEMOX chemotherapy are effective and well-tolerated as a non-first-line therapy in advanced GBC. PD-L1 expression and baseline NLR may potentially predict treatment efficacy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Neoplasias de la Vesícula Biliar , Compuestos de Fenilurea , Receptor de Muerte Celular Programada 1 , Quinolinas , Humanos , Femenino , Masculino , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/mortalidad , Persona de Mediana Edad , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/administración & dosificación , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Retrospectivos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Gemcitabina , Anciano de 80 o más Años , Compuestos Organoplatinos
8.
Front Immunol ; 15: 1449211, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39359732

RESUMEN

Objective: This study aimed to investigate the efficacy, long-term prognosis and safety of combining chemotherapy with regorafenib and immune checkpoint inhibitors as first-line treatment for patients with advanced biliary tract carcinoma (BTC). Methods: In this single arm phase II trial, twenty-nine patients with advanced BTC were included, all of whom received gemcitabine-based chemotherapy combined with regorafenib and immune checkpoint inhibitors as the first-line treatment. And the study analyzed anti-tumor efficacy, long-term prognosis, and adverse reactions. Results: Among the patients, 0 patient achieved complete response, 18 patients (62.1%) achieved partial response, 8 patients (27.6%) had stable disease, and 3 patients (10.3%) experienced progressive disease. The corresponding objective response rate (ORR) was 18/29 (62.1%), and the disease control rate (DCR) was 26/29 (89.7%). The median overall survival (OS) was 16.9 months (95% confidence interval [CI]: 12.0 -21.8) and the median progress free survival (PFS) was 10.2 months (95% CI: 7.8- 12.6). The 1-year OS and PFS were 65% (95% CI: 0.479-0.864) and 41% (95% CI: 0.234-0.656), respectively. The incidence of adverse reactions was 27/29 (93.1%), and the incidence of grade III/IV adverse reactions was 5/29 (17.2%). Conclusion: The combination of chemotherapy, regorafenib, and immune checkpoint inhibitors as a first-line treatment for patients with advanced BTC may has good anti-tumor efficacy without causing serious adverse reactions, and can significantly improve the long-term prognosis.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Sistema Biliar , Inhibidores de Puntos de Control Inmunológico , Compuestos de Fenilurea , Piridinas , Humanos , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Piridinas/efectos adversos , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/mortalidad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Adulto , Resultado del Tratamiento , Gemcitabina , Pronóstico , Estadificación de Neoplasias
9.
Signal Transduct Target Ther ; 9(1): 280, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39384742

RESUMEN

Evidences regarding the feasibility of transcatheter arterial chemoembolization (TACE)-based therapy for unresectable hepatocellular carcinoma (uHCC) remains limited. This study aimed to investigate the efficacy and safety of TACE combined with envafolimab and lenvatinib for uHCC. Eligible patients with uHCC received envafolimab and lenvatinib after TACE until disease progression, conversion to surgery, intolerable toxicities, or death. The primary endpoint was the objective response rate (ORR) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Between March 2022 and July 2022, 38 patients were included for safety analysis, and 36 patients were included for efficacy analysis. As of the data cutoff (13 December 2023), the median follow-up was 16.9 months. The ORR was 50%, and disease control rate (DCR) was 83.3% per RECIST 1.1 (ORR and DCR of both 83.3% per modified RECIST (mRECIST)). The median progression-free survival (PFS) was 7.58 months. Of 36 patients, 17 patients were converted to resectable HCC with a surgical conversion rate of 47.2%, and 16 patients underwent surgery with R0 resection rate of 100%, pathologic complete response (pCR) rate of 31.3%. Overall incidences of treatment-related adverse events (TRAEs) of any grade was 97.4%. Grade ≥ 3 TRAEs were observed in 52.6% patients. No treatment-related deaths occurred. Image mass cytometry (IMC) analysis revealed that combined treatment improved the immune status of the tumor microenvironment, and resident macrophages had the potential to predict efficacy of this treatment. Envafolimab plus lenvatinib and TACE yielded promising survival outcomes and conversion efficiency with a tolerable safety profile. Trial registration Clinical trials: NCT05213221.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/tratamiento farmacológico , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Anciano , Estudios Prospectivos , Adulto , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación
10.
Front Immunol ; 15: 1463574, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39290704

RESUMEN

Background: Currently, the prognosis of advanced intrahepatic cholangiocarcinoma (ICC) is poor, and the current treatment methods are not effective. Objective: The aim of this study was to evaluate the anticancer efficacy of chemotherapy combined with PD-1 inhibitors and tyrosine kinase inhibitors (TKIs) in patients with ICC. Methods: We retrospectively screened patients with advanced intrahepatic cholangiocarcinoma (ICC) who received chemotherapy combined with lenvatinib and PD-1. We evaluated overall survival (OS), progression-free survival (PFS), the objective response rate (ORR), the disease control rate (DCR), the tumor shrinkage rate, and safety. Results: We enrolled 95 patients with ICC and divided them into three groups with a median follow-up duration of 15.1 months. The chemotherapy group (chemo-regimen group), chemotherapy combined with immune checkpoint inhibitors (dual-regimen group), and chemotherapy combined with lenvatinib (triple-regimen group) had median OS times of 13.1 months, 20.8 months, and 39.6 months, respectively. Notably, the triple-regimen group had a significantly longer OS than did the chemo-regimen and dual-regimen groups. The chemo-regimen group, dual-regimen group, and triple-regimen group reported median PFS durations of 4.8 months, 11.9 months, and 23.4 months, respectively. Both combination groups exhibited significantly longer PFS than the chemotherapy-only group (P<0.05). The ORRs of the chemo-regimen, dual-regimen, and triple-regimen groups were 18.2%, 55.5%, and 54.7%, respectively. The DCRs were 72.7%, 90%, and 96.2%, respectively, indicating significantly better outcomes in the combination therapy groups. Conclusion: The combination of chemotherapy with PD-1 inhibitors and lenvatinib demonstrates considerable efficacy and tolerability as a treatment strategy for patients with advanced ICC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Compuestos de Fenilurea , Receptor de Muerte Celular Programada 1 , Quinolinas , Humanos , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/mortalidad , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/mortalidad , Adulto , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Resultado del Tratamiento , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos
11.
BMC Cancer ; 24(1): 1215, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39350084

RESUMEN

BACKGROUND: Heterogeneity of hepatocellular carcinoma (HCC) presents significant challenges for therapeutic strategies and necessitates combinatorial treatment approaches to counteract suppressive behavior of tumor microenvironment and achieve improved outcomes. Here, we employed cytokines to induce memory-like behavior in natural killer (NK) cells, thereby enhancing their cytotoxicity against HCC. Additionally, we evaluated the potential benefits of combining sorafenib with this newly developed memory-like NK cell (pNK) immunochemotherapy in a preclinical model. METHODS: HCC tumors were grown in SD rats using subcapsular implantation. Interleukin 12/18 cytokines were supplemented to NK cells to enhance cytotoxicity through memory activation. Tumors were diagnosed using MRI, and animals were randomly assigned to control, pNK immunotherapy, sorafenib chemotherapy, or combination therapy groups. NK cells were delivered locally via the gastrointestinal tract, while sorafenib was administered systemically. Therapeutic responses were monitored with weekly multi-parametric MRI scans over three weeks. Afterward, tumor tissues were harvested for histopathological analysis. Structural and functional changes in tumors were evaluated by analyzing MRI and histopathology data using ANOVA and pairwise T-test analyses. RESULTS: The tumors were allowed to grow for six days post-cell implantation before treatment commenced. At baseline, tumor diameter averaged 5.27 mm without significant difference between groups (p = 0.16). Both sorafenib and combination therapy imposed greater burden on tumor dimensions compared to immunotherapy alone in the first week. By the second week of treatment, combination therapy had markedly expanded its therapeutic efficacy, resulting in the most significant tumor regression observed (6.05 ± 1.99 vs. 13.99 ± 8.01 mm). Histological analysis demonstrated significantly improved cell destruction in the tumor microenvironment associated with combination treatment (63.79%). Interestingly, we observed fewer viable tumor regions in the sorafenib group (38.9%) compared to the immunotherapy group (45.6%). Notably, there was a significantly higher presence of NK cells in the tumor microenvironment with combination therapy (34.79%) compared to other groups (ranging from 2.21 to 26.50%). Although the tumor sizes in the monotherapy groups were similar, histological analysis revealed a stronger response in pNK cell immunotherapy group compared to the sorafenib group. CONCLUSIONS: Experimental results indicated that combination therapy significantly enhanced treatment response, resulting in substantial tumor growth reduction in alignment with histological analysis.


Asunto(s)
Carcinoma Hepatocelular , Células Asesinas Naturales , Neoplasias Hepáticas , Sorafenib , Sorafenib/uso terapéutico , Sorafenib/farmacología , Animales , Células Asesinas Naturales/inmunología , Ratas , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/tratamiento farmacológico , Inmunoterapia/métodos , Humanos , Terapia Combinada , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Masculino , Niacinamida/análogos & derivados , Niacinamida/uso terapéutico , Niacinamida/farmacología , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/farmacología , Memoria Inmunológica/efectos de los fármacos , Línea Celular Tumoral , Modelos Animales de Enfermedad
12.
Front Immunol ; 15: 1466113, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39281676

RESUMEN

Background: Locoregional treatment combined with systemic therapy is expected to play a synergistic anticancer role. We conducted this systemic meta-analysis to examine the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib with or without programmed cell death protein-1 (PD-1) inhibitors (TLP group) compared with TACE + lenvatinib (TL group) for unresectable hepatocellular carcinoma (uHCC). Methods: From the inception date to April 2024, the data from PubMed, EMBASE, the Cochrane Library, Ovid, Web of Science, and Clinical Trials. gov were used for meta-analysis. All clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CI) were used to measure the pooled effect. Results: This study included 10 retrospective cohort studies, including 1128 patients. The OS (HR=0.51; 95% CI: 0.43-0.60, P < 0.05), PFS (HR=0.52; 95% CI: 0.45-0.61, P < 0.05), ORR (RR = 1.58; 95% CI: 1.37-1.83; P < 0.05) and DCR (RR = 1.31; 95% CI: 1.20-1.43; P < 0.05) were significantly higher in TLP group than in the TL group. The incidence of AEs was acceptable. Prognostic factor analysis identified that ECOG PS (1/0), Child-Pugh class (B/A), BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for OS. BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for PFS. Conclusion: The TLP group had better efficacy for uHCC than that of the TL group, with acceptable safety. Systematic review registration: PROSPERO, identifier (CRD42023420093).


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Quimioembolización Terapéutica/efectos adversos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Resultado del Tratamiento
13.
Lancet ; 404(10460): 1309-1320, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39284329

RESUMEN

BACKGROUND: Immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor receptor tyrosine kinase inhibitors are cornerstones of first-line treatment for advanced renal cell carcinoma; however, optimal treatment sequencing after progression is unknown. This study aimed to assess clinical outcomes of tivozanib-nivolumab versus tivozanib monotherapy in patients with metastatic renal cell carcinoma who have progressed following one or two lines of therapy in the post-ICI setting. METHODS: TiNivo-2 is a multicentre, randomised, open-label, phase 3 trial at 190 sites across 16 countries, in Australia, Europe, North America, and South America. Patients with advanced renal cell carcinoma and progression during or after one to two previous lines of therapy (including one ICI) were randomised 1:1 to tivozanib (0·89 mg per day, orally) plus nivolumab (480 mg every 4 weeks, intravenously) or tivozanib (1·34 mg per day, orally). Randomisation was stratified by immediate previous therapy (ICI or non-ICI) and International Metastatic Renal Cell Carcinoma Database Consortium risk category. The primary endpoint was progression-free survival (PFS), defined as the time from randomisation to first documentation of objective progressive disease according to RECIST 1·1 or death from any cause, whichever came first, by independent radiology review. Efficacy was evaluated in the intention-to-treat population, and safety was assessed in patients who received one or more doses of the study drug. This trial was registered on ClinicalTrials.gov (NCT04987203) and is active and not recruiting. FINDINGS: From Nov 4, 2021, to June 16, 2023, 343 patients were randomly assigned to tivozanib-nivolumab (n=171) or tivozanib monotherapy (n=172). Median follow-up was 12·0 months. Median PFS was 5·7 months (95% CI 4·0-7·4) with tivozanib-nivolumab and 7·4 months (5·6-9·2) with tivozanib monotherapy (hazard ratio 1·10, 95% CI 0·84-1·43; p=0·49). Among those with an ICI as their immediate previous therapy (n=244), median PFS was 7·4 months (95% CI 5·6-9·6) with tivozanib-nivolumab and 9·2 months (7·4-10·0) with tivozanib monotherapy. With non-ICIs as the most recent therapy, lower median PFS was observed, with no difference between groups (tivozanib-nivolumab 3·7 months [95% CI 2·7-5·4] and with tivozanib monotherapy 3·7 months [1·9-7·2]). Serious adverse events occurred in 54 (32%) of 168 patients receiving tivozanib-nivolumab and 64 (37%) of 171 patients receiving tivozanib monotherapy. One (<1%) treatment-related death occurred (tivozanib group). INTERPRETATION: These data further support that ICI rechallenge should be discouraged in patients with advanced renal cell carcinoma. Furthermore, these data suggest that tivozanib monotherapy has efficacy in the post-ICI setting. FUNDING: Aveo Pharmaceuticals.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Renales , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales , Nivolumab , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Nivolumab/uso terapéutico , Nivolumab/efectos adversos , Nivolumab/administración & dosificación , Masculino , Femenino , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Persona de Mediana Edad , Anciano , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Supervivencia sin Progresión , Adulto
14.
Cancer Med ; 13(18): e70217, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39300938

RESUMEN

INTRODUCTION: This study aimed to evaluate the efficacy and safety of atezolizumab combined with bevacizumab (Atez/Bev) compared to lenvatinib (LEN) as first-line systemic therapy for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) exceeding the up-to-seven criteria threshold, who are typically unsuitable for transarterial chemoembolization (TACE). METHODS: A retrospective analysis was conducted on 49 consecutive patients with HCC treated at Tokyo Metropolitan Komagome Hospital between May 2018 and October 2023. The patients were divided into two groups: the Atez/Bev group (21 patients) and the LEN group (28 patients). Eligibility criteria included Child-Pugh A classification, no prior systemic therapy, and ineligibility for resection, ablation, or transplantation. Treatment outcomes were assessed through periodic imaging and laboratory tests, evaluating OS, PFS, ORR, and disease control rate (DCR). RESULTS: Both groups demonstrated comparable baseline characteristics, with a median follow-up of 15.4 months. No significant difference was observed in OS between the Atez/Bev and LEN groups (median OS: 19.80 vs. 22.20 months, p = 0.763). The median PFS was 10.23 months for Atez/Bev and 7.20 months for LEN (p = 0.343). There were no statistically significant differences in ORR or DCR between the two groups. Common adverse events included elevated AST and ALT levels, with no significant difference in the overall rate of adverse events between the groups. CONCLUSIONS: Atez/Bev and LEN demonstrated comparable efficacy and safety as first-line systemic treatments for patients with BCLC stage B HCC exceeding the up-to-seven criteria. Both therapeutic options are viable for this population, though further large-scale prospective studies are required to confirm these findings.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Masculino , Femenino , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Estudios Retrospectivos , Anciano , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Persona de Mediana Edad , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estadificación de Neoplasias , Anciano de 80 o más Años , Adulto , Resultado del Tratamiento
15.
Expert Opin Drug Metab Toxicol ; 20(9): 907-922, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39225462

RESUMEN

INTRODUCTION: Hepatocellular carcinoma (HCC) accounts for 85% of liver cancer cases and is the third leading cause of cancer death. Regorafenib is a multi-target inhibitor that dramatically prolongs progression-free survival in HCC patients who have failed sorafenib therapy. However, one of the primary factors limiting regorafenib's clinical utilization is toxicity. Using Clinical Trials.gov and PubMed, we gathered clinical data on regorafenib and conducted a extensive analysis of the medication's adverse reactions and mechanisms. Next, we suggested suitable management techniques to improve regorafenib's effectiveness. AREAS COVERED: We have reviewed the mechanisms by which regorafenib-induced toxicity occurs and general management strategies through clinical trials of regorafenib. Furthermore, by examining the literature on regorafenib and other tyrosine kinase inhibition, we summarized the mechanics of the onset of regorafenib toxicity and mechanism-based intervention strategies by reviewing the literature related to regorafenib and other tyrosine kinase inhibition. EXPERT OPINION: One of the primary factors restricting regorafenib's clinical utilization and combination therapy is its toxicity reactions. To optimize regorafenib treatment regimens, it is especially important to further understand the specific toxicity mechanisms of regorafenib as a multi-kinase inhibitor.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Compuestos de Fenilurea , Inhibidores de Proteínas Quinasas , Piridinas , Humanos , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/administración & dosificación , Piridinas/efectos adversos , Piridinas/administración & dosificación , Piridinas/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/administración & dosificación , Animales , Supervivencia sin Progresión
16.
J Cancer Res Clin Oncol ; 150(9): 427, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39302490

RESUMEN

BACKGROUND: The treatment of unresectable hepatocellular carcinoma (uHCC) challenging due to unfulfilled clinical requirements. OBJECTIVE: To evaluate the safety and efficacy of combining transarterial chemoembolization (TACE) with sintilimab and lenvatinib in the treatment of uHCC. METHODS: We retrospectively analyzed the data of patients with uHCC who were treated with a combination of TACE, sintilimab, and lenvatinib between May 2019 and December 2021 at the Chinese PLA General Hospital. Systemic treatment was started 1 week after TACE was performed. Sintilimab was administered intravenously at a dosage of 200 mg every three weeks, and lenvatinib was given orally at dosages of 8 mg or 12 mg daily, contingent upon the weight of the patients. The primary endpoint was the objective response rate (ORR) as per the mRECIST. Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (tr-AEs). RESULTS: A total of 32 patients were enrolled in the study. Among them, 9 patients were classified as Barcelona Clinic Liver Cancer-B (BCLC-B), 23 patients were classified as BCLC-C, 14 patients diagnosed with portal vein tumors, and 12 patients were diagnosed with extra hepatic metastases. The ORR and DCR were 75% and 90.6% respectively, with 4 patients exhibiting (12.5%) complete response, 20 patients exhibiting (62.5%) partial response, 5 patients exhibiting (15.6%) stable disease, and 3 patients exhibiting (9.4%) progressive disease. With a median follow-up time of 19.6 months, the median PFS was 9.9 months, and the median OS was 33.3 months. A total of 31 patients experienced different degrees of tr-AEs, of which 2 were grade 3 tr-AEs. CONCLUSION: The combination therapy of TACE, sintilimab, and lenvatinib demonstrates satisfactory efficacy in the treatment of uHCC with manageable tr-AEs.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Masculino , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , Femenino , Quimioembolización Terapéutica/métodos , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto
17.
J Cancer Res Ther ; 20(4): 1344-1349, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39206997

RESUMEN

BACKGROUNDS: Programmed death receptor 1 (PD-1) monoclonal antibody has been approved for the first and second-line treatments of hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy and safety of tislelizumab + regorafenib as a second-line treatment option for advanced HCC. METHODS: Treatment-related adverse events (TRAEs) were the primary endpoints in this clinical trial comprising 28 patients with advanced HCC. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). RESULTS: According to the mRECIST 1.1 evaluation criteria, the ORR was 28.6%. Complete and partial response were observed in 3 and 5 patients, respectively; stable disease was observed in 12 patients (DCR, 71.4%). The median PFS was 6.4 months. The incidence of grade 1-2 and 3-4 TRAEs was 57.1% and 39.3%, respectively. CONCLUSION: This study suggests that tislelizumab + regorafenib can be used as a second-line treatment for advanced HCC.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Neoplasias Hepáticas , Compuestos de Fenilurea , Piridinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Piridinas/uso terapéutico , Piridinas/administración & dosificación , Piridinas/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Estudios Prospectivos , Adulto , Resultado del Tratamiento
18.
Turk J Gastroenterol ; 35(3): 212-222, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39128062

RESUMEN

BACKGROUND/AIMS:  At present, there are relatively few reports on the treatment consisting of transarterial chemoembolization (TACE) combined with lenvatinib, and there is no unified conclusion on the curative effect. The objective of this research was to assess the efficacy and safety of combining TACE with lenvatinib for the treatment of unresectable hepatocellular carcinoma (uHCC). MATERIALS AND METHODS:  This study was a retrospective analysis of the patient's medical records. In this study, 249 patients (uHCC) in our hospital from 2020 to 2021 were divided into 2 groups, including the TACE-alone group (198 patients received TACE alone) and the TACE-LEN group (51 patients were treated with TACE combined with lenvatinib). According to the propensity score matching method, there were TACE-LEN group (51 patients) and TACE-alone group (51 patients). With the help of surgical experts, the overall survival (OS), progression-free survival (PFS), and tumor response (according to mRECIST) of the 2 groups were sorted and recorded, and then analyzed. Survival curves were established, the prognostic factors of OS and PFS were analyzed by univariate and multivariate analyses, and the independent prognostic factors were recorded. The adverse reactions of patients after treatment were recorded. RESULTS:  The 1-year and 2-year OS rates were 50.98% and 19.48% for the TACE-LEN group, 27.45% and 8.55% for the TACE-alone group (P = .042), respectively. The PFS of patients in the TACE-LEN group was also longer (1-year PFS rate: 25.49% vs. 11.76%, 2-year PFS rate: 19.17% vs. 5.88%; P = .0069). The disease control rate (68.63% vs. 49.10%, P = .044) of the TACE-LEN group was significantly higher. In the subgroup analysis, the OS of the TACE-LEN group was better than TACE-alone group in patients with Barcelona Clinic Liver Cancer stage C (1-year OS rate: 44.44% vs. 17.14%, 2-year OS rate: 8.67% vs. 0%; P = .009). Factor analysis concluded that serum alkaline phosphatase and treatment protocol (TACE-LEN vs. TACE) were independent influencing factors of OS. The most common treatment-related AEs included decreased albumin (n = 28, 54.9%), hypertension (n = 23, 45.1%), elevated aspartate transaminase (n = 21, 41.2%) and elevated total bilirubin (n = 18, 35.2%) in TACE-LEN group. CONCLUSION:  Compared with TACE monotherapy, TACE combined with lenvatinib effectively prolonged the OS time with a controllable safety profile for patients with uHCC.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Quimioembolización Terapéutica/métodos , Estudios Retrospectivos , Femenino , Masculino , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Persona de Mediana Edad , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Anciano , Antineoplásicos/administración & dosificación , Resultado del Tratamiento , Terapia Combinada , Puntaje de Propensión
19.
Cancer Med ; 13(16): e70065, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39190576

RESUMEN

AIM: Lenvatinib mesylate (LEN) is an oral tyrosine kinase inhibitor used to treat various cancers, including hepatocellular carcinoma (HCC). HCC treatment with LEN is associated with a very high incidence of adverse events. This study was aimed at investigating the incidence of LEN-induced palmar-planter erythrodysesthesia syndrome (PPES) and its relationship with patient demographics by analyzing clinical laboratory data of LEN-treated patients with HCC. METHODS: This was a single-centre, retrospective study of patients with HCC who received LEN between April 19, 2018, and September 30, 2020. The observation period was from 1 week before the start of LEN administration to 1 month after the end of administration. RESULTS: Overall, 75 patients with HCC were enrolled. LEN-induced PPES was found in 48.0% (36/75 patients). In these patients, alkaline phosphatase (ALP), γ-Glutamyl transpeptidase (γ-GTP) and monocytes (MONO) were significantly high (ALP: p = 1.32 × 10-3, γ-GTP: p = 4.25 × 10-3 and MONO: p = 0.013). The cut off values of ALP, γ-GTP and MONO for LEN-induced PPES were estimated at 573 U/L, 89 U/L, and 310 counts/µL, respectively. In the multivariate analysis, γ-GTP and MONO were independent risk factors for LEN-induced PPES. CONCLUSIONS: High γ-GTP and high MONO were risk factors for LEN-induced PPES.


Asunto(s)
Carcinoma Hepatocelular , Síndrome Mano-Pie , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Masculino , Neoplasias Hepáticas/tratamiento farmacológico , Estudios Retrospectivos , Femenino , Anciano , Quinolinas/efectos adversos , Quinolinas/uso terapéutico , Persona de Mediana Edad , Factores de Riesgo , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/administración & dosificación , Síndrome Mano-Pie/etiología , Síndrome Mano-Pie/epidemiología , gamma-Glutamiltransferasa/sangre , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Fosfatasa Alcalina/sangre , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Incidencia , Monocitos/efectos de los fármacos , Adulto
20.
Front Immunol ; 15: 1430571, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39131156

RESUMEN

Background: Intermediate-stage (BCLC-B) hepatocellular carcinoma (HCC) beyond the up-to-11 criteria represent a significant therapeutic challenge due to high and heterogeneous tumor burden. This study evaluated the effectiveness and safety of transarterial chemoembolization (TACE) in combination with lenvatinib and tislelizumab for these patients. Methods: In this retrospective cohort study, patients with unresectable intermediate-stage HCC beyond the up-to-11 criteria were enrolled and divided into TACE monotherapy (T), TACE combined with lenvatinib (TL), or TACE plus lenvatinib and tislelizumab (TLT) group based on the first-line treatment, respectively. The primary endpoint was overall survival (OS). The secondary outcomes included progression-free survival (PFS), tumor response according to RESIST1.1 and modified RECIST, and adverse events (AEs). Results: There were 38, 45, and 66 patients in the T, TL, and TLT groups, respectively. The TLT group exhibited significantly higher ORR and DCR than the other two groups, as assessed by either mRECIST or RECIST 1.1 (all P<0.05). Median PFS and OS were significantly longer in the TLT group compared with the T group (PFS: 8.5 vs. 4.4 months; OS: 31.5 vs. 18.5 months; all P<0.001) and TL group (PFS: 8.5 vs. 5.5 months; OS: 31.5 vs. 20.5 months; all P<0.05). The incidence of TRAEs was slightly higher in the TLT and TL groups than in the T group, while all the toxicities were tolerable. No treatment-related death occurred in all groups. Conclusions: TACE combined with lenvatinib and tislelizumab significantly improved the survival benefit compared with TACE monotherapy and TACE plus lenvatinib in patients with intermediate-stage HCC beyond the up-to-11 criteria, with an acceptable safety profile.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/tratamiento farmacológico , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Quimioembolización Terapéutica/métodos , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Estudios Retrospectivos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Estadificación de Neoplasias , Resultado del Tratamiento
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