RESUMO
BACKGROUND: Anlotinib has demonstrated promising anti-tumor efficacy in various solid tumors. Additionally, there is evidence suggesting that immune therapy can enhance the systemic responses of anlotinib. This study aimed to assess the effectiveness and safety of combining anlotinib with PD-1 inhibitors compared to fluoropyrimidine-based chemotherapy as a second-line treatment option for advanced biliary tract cancers (BTCs). METHODS: A total of 242 patients with BTCs were screened at the First Affiliated Hospital of Zhengzhou University from October 2015 to October 2022. Among them, 78 patients who received either anlotinib plus PD-1 inhibitors (AP) or fluoropyrimidine-based chemotherapy (FB) as second-line treatment were included in the study. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety, and predictive tumor biomarkers. RESULTS: Among the 78 patients with BTCs, 39 patients received AP, while 39 patients were administered FB. The ORR in the AP group was 20.5%, compared to 5.1% in the FB group. The DCR was 87.2% in the AP group and 66.7% in the FB group. The AP group demonstrated significantly better ORR and DCR compared to the FB group (p = 0.042, p = 0.032). The median PFS and OS in the AP group were 7.9 months (95% CI: 4.35-11.45) and 13.9 months (95% CI: 5.39-22.41), respectively. In the FB group, the median PFS and OS were 4.1 months (95% CI: 3.17-5.03) and 13.2 months (95% CI: 8.72-17.68), respectively. The AP group exhibited significantly better median PFS than the FB group (p = 0.027). In the subgroup analysis, patients without liver metastasis had a much longer PFS in the AP group compared to the FB group (14.3 vs. 5.5 months, p = 0.016). Similarly, patients with CEA ≤ 5 µg/L also demonstrated a longer PFS in the AP group compared to the FB group (8.7 vs. 3.9 months, p = 0.008). CONCLUSIONS: The combination of anlotinib and PD-1 inhibitors demonstrated a promising clinical effect compared to fluoropyrimidine-based chemotherapy in the second-line treatment of refractory advanced BTCs. Liver metastases and CEA levels may serve as predictive factors for identifying patients who may benefit from AP therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar , Inibidores de Checkpoint Imunológico , Indóis , Quinolinas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Quinolinas/uso terapêutico , Quinolinas/efeitos adversos , Quinolinas/administração & dosagem , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/mortalidade , Idoso , Indóis/uso terapêutico , Indóis/administração & dosagem , Indóis/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Intervalo Livre de Progressão , Estudos Retrospectivos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: In oncology, we tend to look for factors that reflect better prognosis or predict response to treatments in order to make a selection from which patients will derive the benefit, avoiding futile therapies and/or toxicities. Definitive prognostic and predictive factors in advanced biliary cancer remain unknown. METHODS: We retrospectively analyzed all consecutive patients in our institution with advanced biliary tract cancer treated with palliative cisplatin plus gemcitabine. We evaluated the prognostic and predictive role of the immunohistochemistry (IHC) expression of ERCC1 (excision cross-complementing gene-1) on tumor response and also examined several clinical and laboratory prognostic factors for overall survival. RESULTS: From January 2009 to July 2011, 72 patients were identified; their median overall survival was 9.5 months. Independent variables associated with shorter survival identified by the multivariable Cox regression analysis were ECOG 2-3 (HR 8.4; 95% CI 3.4 to 20.7; p < 0.001) and Charlson Comorbidity Index >1 (HR 9.5; 95% CI 1.6 to 55.3; p = 0.012). Pathology slides were available from 44 patients: 23 (52%) stained positive for ERCC1 on IHC (score ≥0.5). In this subgroup, expression of ERCC-1 was not prognostic and was not associated with either clinical benefit (partial response and stable disease) or tumor response (partial response only) to chemotherapy. CONCLUSIONS: In this cohort of unselected patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin, IHC expression of ERCC1 was not either predictive or prognostic. Patients with ECOG 2-3 and/or multiple comorbidities had worse survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , GencitabinaRESUMO
BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a widely used technique for the diagnosis and treatment of bilio-pancreatic diseases. According to Mexican Statistics, there is increasing life expectancy in Mexican population. The incidence of biliary tract pathologies is also increasing, leading to an increased demand of ERCP. AIM: Compare the utility and safety of ERCP in elderly and younger patients. METHODS: Prospective and comparative study including 450 patients who underwent ERCP during 2007. Patients were divided into two groups: 65 years age and older (group A) and less than 65 years old (group B). We registered gender, age, indication and length of the endoscopic procedure, morbidity and mortality. RESULTS: Mean patient age was 74.5 ± 6.9 and 43.0 ± 13.5 years old in groups A and B respectively. Choledocholithiasis was the more frequent diagnosis in both groups (48.62 %), followed by benign biliary stenosis (22.02 %) and malignant biliary obstruction (16.28 %). In 428 patients (98.16%) therapeutic procedures were performed. Endoscopic complications occurred in 1.37 % and there were not significant differences between groups (p = 0.218). There was no mortality. CONCLUSION: ERCP is a safe procedure in elderly patients with a very low rate of complications and excellent therapeutic efficacy.
Assuntos
Doenças Biliares/cirurgia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doenças Biliares/epidemiologia , Doenças Biliares/mortalidade , Neoplasias do Sistema Biliar/epidemiologia , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/cirurgia , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Estudos ProspectivosRESUMO
This epidemiological study in Chile shows a marked increase in biliary-tract cancer based on mortality data, from an age-adjusted rate (1970 world population) of 5.1 per 100,000 in 1970 to 12.0 per 100,000 in 1988. There is an increased risk of this cancer in all age groups but especially in young adults (15-44 years). The female ratio of 3:1 persists. The increase in biliary-tract cancer in 1970-1985 was particularly important for young women but occurred in all female age groups whereas in men it was mostly in the elderly (65 years and more) and less in the middle-aged (45-64 years); no changes were observed in young men. Regional differences have begun to be appreciated. One of the factors which may account for this impressive and unexpected increase is the remarkable decrease in cholecystectomy rates. Less than 20% of the 154% increase in biliary-tract cancer mortality in the period 1970-1985 could be attributed to population aging. Improvements in diagnostic methods did not appear to be an important contributing factor. Other factors that could affect this increase in the incidence to epidemic levels include: an increase in the prevalence of cholelithiasis, an increase in the number of typhoid carriers and possible environmental carcinogens.
Assuntos
Neoplasias do Sistema Biliar/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Chile/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores SexuaisRESUMO
Se analiza la mortalidad de los tres principales cánceres en Chile: gástrico, pulmonar y biliar. Mientras el primero disminuye notablemente entre 1970 y 1985 (de 32.7 a 18.6 por 100.000), el pulmonar aumenta en forma moderada (de 7.6 a 10.7) y el biliar lo hace en forma extraordinaria (de 3.7 a 9.4). Las tendencias observadas permiten pronosticar con algún fundamento y en ausencia de programas efectivos de control que dichas tendencias se mantendrán en el próximo decenio, revirtiendo la importancia relativa de estos cánceres y confirmando al cáncer biliar como primera causa de muerte oncológica en Chile por encima del pulmonar y del gástrico en el próximo decenio. Esto empeoraría la situación actual de ser ya el primero en la mujer (desde 1985), por encima del gástrico, cérvico-uterino y mamario