RESUMO
PURPOSE: To assess the efficacy and safety of concurrent hypofractionated radiotherapy plus anti-PD-1 antibody and SOX chemotherapy in the treatment of metastatic pancreatic cancer (mPC) after failure of first-line chemotherapy. METHODS: Patients with pathologically confirmed mPC who failed standard first-line chemotherapy were enrolled. The patients were treated with a regimen of hypofractionated radiotherapy, SOX chemotherapy, and immune checkpoint inhibitors at our institution. We collected the patients' clinical information and outcome measurements. The median progression-free survival (mPFS) was the primary endpoint of the study, followed by disease control rate (DCR), objective response rate (ORR), median overall survival (mOS) and safety. Exploratory analyses included biomarkers related to the benefits. RESULTS: Between February 24, 2021, and August 30, 2023, twenty-five patients were enrolled in the study, and twenty-three patients who received at least one dose of the study agent had objective efficacy evaluation. The mPFS was 5.48 months, the mOS was 6.57 months, and the DCR and ORR were 69.5% and 30.4%, respectively. Among the seven patients who achieved a PR, the median duration of the response was 7.41 months. On-treatment decreased serum CA19-9 levels were associated with better overall survival. Besides, pretreatment inflammatory markers were associated with tumor response and survival. CONCLUSIONS: Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with these combination therapies in patients with refractory mPC. On-treatment decreased serum CA19-9 levels and pretreatment inflammatory markers platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH) might be biomarkers related to clinical benefits. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.html?proj=130211 , identifier: ChiCTR2100049799, date of registration: 2021-08-09.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Hipofracionamento da Dose de Radiação , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Inibidores de Checkpoint Imunológico/uso terapêutico , Ácido Oxônico/uso terapêutico , Ácido Oxônico/administração & dosagem , Quimiorradioterapia/métodos , Tegafur/uso terapêutico , Tegafur/administração & dosagem , Gencitabina , Metástase NeoplásicaRESUMO
PURPOSE: To describe the real-world treatment patterns of systemic therapies for biliary tract cancer (BTC) and to examine the frequency and management of biliary infection in Japan. METHODS: Patients diagnosed with BTC and prescribed systemic therapy between January 2011 and September 2020 were retrieved from the Japanese Medical Data Vision database. The look-back period was set to 5 years. Patient characteristics, treatment patterns, and biliary infection-induced treatment interruption were analyzed. RESULTS: The full analysis set comprised 22 742 patients with a mean age of 71.0 years and 61.6% were male. The most common BTC type was extrahepatic cholangiocarcinoma (44.6%). The three most common first-line regimens were S-1 monotherapy (33.0%), gemcitabine+cisplatin (32.5%), and gemcitabine monotherapy (18.7%) over the entire observation period (January 2011-September 2021). Patients who received monotherapies tended to be older. Biliary infection-induced treatment interruption occurred in 29.5% of patients, with a median time to onset of 64.0 (interquartile range 29.0-145.0) days. The median duration of intravenous antibiotics was 12.0 (interquartile range 4.0-92.0) days. CONCLUSIONS: These results demonstrated potential challenges of BTC in Japanese clinical practice particularly use of multiple regimens, commonly monotherapies, which are not recommended as first-line treatment, and the management of biliary infections during systemic therapy.
Assuntos
Neoplasias do Sistema Biliar , Bases de Dados Factuais , Humanos , Masculino , Feminino , Idoso , Japão , Neoplasias do Sistema Biliar/tratamento farmacológico , Pessoa de Meia-Idade , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Gencitabina , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Combinação de Medicamentos , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricosRESUMO
Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX are widely used as first-line regimens for unresectable pancreatic cancer (PC). When GnP therapy is selected, considering patient age or condition, second-line FOLFIRINOX is sometimes difficult to administer owing to its toxicity. This study aimed to determine the recommended dose (RD) of S-IROX (S-1, oxaliplatin, and irinotecan combination) regimens in patients with unresectable PC after first-line GnP failure. This phase-I study used the "3 + 3" dose-escalation design with two dose levels. Patients who failed first-line GnP therapy for unresectable PC were enrolled. Oxaliplatin and irinotecan were administered on day 1, and S-1 was administered orally twice daily on days 1-7, followed by 7 days of rest. The primary endpoints were dose-limiting toxicities (DLTs) and determination of RD. The secondary endpoint was the evaluation of potential antitumor activity. Nine patients received the second-line S-IROX regimen. In level-0 (S-1, 80 mg/m2; oxaliplatin, 85 mg/m2; and irinotecan, 120 mg/m2), no patient experienced DLT; however, one patient experienced grade 3 neutropenia. At level-1 (irinotecan increased to 150 mg/m2), one of six patients experienced DLTs, including G3 diarrhea. The RD was confirmed at the level-1 dose. The response rate, disease control rate, median progression-free survival, and median overall survival were 33.3%, 77.8%, 172 (range:77-422) days, and 414 (101-685) days, respectively. One patient underwent surgery after the second-line S-IROX therapy. Second-line S-IROX treatment was deemed acceptable. The RD was set at level-1 dose (S-1, 80 mg/m2; oxaliplatin, 85 mg/m2; and irinotecan, 150 mg/m2).
Assuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Combinação de Medicamentos , Gencitabina , Irinotecano , Oxaliplatina , Ácido Oxônico , Paclitaxel , Neoplasias Pancreáticas , Tegafur , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso , Albuminas/administração & dosagem , Albuminas/uso terapêutico , Albuminas/efeitos adversos , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Oxaliplatina/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Irinotecano/administração & dosagem , Irinotecano/uso terapêutico , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Tegafur/uso terapêutico , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Ácido Oxônico/uso terapêutico , AdultoRESUMO
INTRODUCTION: This multicenter phase I/IIa study aimed to determine the recommended phase II dose (RP2D) and evaluate the safety and preliminary efficacy of liposomal irinotecan (nal-IRI), oxaliplatin, and S-1 (NASOX) as first-line treatment for advanced pancreatic adenocarcinoma. METHODS: Patients with locally advanced or metastatic pancreatic adenocarcinoma without prior systemic treatment for advanced disease, aged ≥ 19 years, with measurable disease, and Eastern Cooperative Oncology Group performance status of 0-1 were eligible. The primary endpoints were to determine the dose-limiting toxicity (DLT) in the phase I cohort and overall response rate (ORR) in the phase IIa cohort. The intention-to-treat (ITT) analysis included patients who received the RP2D. RESULTS: In phase I, seven patients were screened, and six were assessed for DLT. None experienced DLT during the first cycle. The RP2D was determined as nal-IRI 50 mg/m2 and oxaliplatin 60 mg/m2 on day 1, S-1 40 mg/m2 twice daily on days 1-7 every 14 days. For the ITT (N = 41; 7, and 34 from phases I and IIa, respectively), the most common grade 3-4 treatment-emergent adverse events were neutropenia (31.7 %), enterocolitis (9.8 %), anorexia (7.3 %), and diarrhea (2.4 %). The ORR was 58.5 % (1 complete, and 23 partial responses). Two underwent conversion surgery; both achieved R0 resection. With median follow-up of 17.5 months, median progression-free survival was 6.5 months (95 % confidence interval [CI], 5.0-8.1) and median overall survival was 11.4 months (95 % CI, 9.8-15.5). CONCLUSION: NASOX exhibited a manageable safety profile and encouraging efficacy outcomes consistent with NALIRIFOX, showing potential to replace infusional 5-fluorouracil with oral S-1 in the triplet regimen.
Assuntos
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Combinação de Medicamentos , Irinotecano , Oxaliplatina , Ácido Oxônico , Neoplasias Pancreáticas , Tegafur , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Masculino , Irinotecano/uso terapêutico , Irinotecano/administração & dosagem , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Oxaliplatina/efeitos adversos , Feminino , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Ácido Oxônico/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Tegafur/efeitos adversos , Lipossomos , Adulto , Intervalo Livre de ProgressãoRESUMO
Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1. In this single-center, retrospective study, GC patients after D2 gastrectomy received either nab-paclitaxel plus S-1 (AS group) or SOX group were recruited between January 2018 and December 2020 in The First Affiliated Hospital of Zhejiang University. Intravenous nab-paclitaxel 120 mg/m2 or 260 mg/m2 and oxaliplatin 130 mg/m2 were administered as eight 3 week cycle, especially in the AS and SOX group. Patients received S-1 twice daily with a dose of 40 mg/m2 in the two groups on days 1-14 of each cycle. The end points were disease-free survival (DFS) rate at 3 years and adverse events (AEs). There were 56 eligible patients, 28 in the AS group and 35 in the SOX group. The 3 year DFS rate was 78.0% in AS group versus 70.7% in SOX group (p = 0.46). Subgroup analysis showed that the patients with signet-ring positive in the AS group had a prolonged DFS compared with the SOX group (40.0 vs. 13.8 m, p = 0.02). The diffuse-type GC or low differentiation in the AS group was associated with numerically prolonged DFS compared with the SOX group, but the association was not statistically significant (p = 0.27 and p = 0.15 especially). Leukopenia (14.3%) were the most prevalent AEs in the AS group, while thrombocytopenia (28.5%) in the SOX group. Neutropenia (7.1% in AS group) and thrombocytopenia (22.8% in SOX group) were the most common grade 3 or 4 AEs. In this study analyzing past data, a tendency towards a greater 3 year DFS was observed when using AS regimen in signet-ring positive patients. AS group had fewer thrombocytopenia compared to SOX group. More studies should be conducted with larger sample sizes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Combinação de Medicamentos , Gastrectomia , Oxaliplatina , Ácido Oxônico , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Masculino , Feminino , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Tegafur/uso terapêutico , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Estudos Retrospectivos , Gastrectomia/métodos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Ácido Oxônico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso , Quimioterapia Adjuvante/métodos , Paclitaxel Ligado a Albumina/administração & dosagem , Paclitaxel Ligado a Albumina/uso terapêutico , Adulto , Intervalo Livre de Doença , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Paclitaxel/efeitos adversos , Albuminas/administração & dosagemRESUMO
This study aimed to compare second-line treatment outcomes for patients with unresectable pancreatic cancer previously treated with gemcitabine plus nab-paclitaxel (GnP) therapy. We conducted an integrated analysis of two retrospective studies included 318 patients receiving nanoliposomal irinotecan + 5-fluorouracil/folinic acid (NFF) (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment. Median overall survival (OS) in the NFF group was 9.08 months, significantly better than S-1 (4.90 months, P = 0.002). FOLFIRINOX had a median OS of 4.77 months, not statistically different from NFF. Subgroup analyses of OS indicated NFF was generally superior, however, a statistical interaction was observed between the treatment regimen in serum Alb < 3.5 g/dL (P = 0.042) and serum CRP ≥ 0.3 mg/dL (P = 0.006). Median progression-free survival (PFS) was 2.93 months for NFF, significantly better than S-1 (2.53 months, P = 0.024), while FOLFIRINOX had a comparable PFS (3.04 months, P = 0.948). Multivariate analysis identified the serum CRP, serum CA19-9, duration of first-line GnP therapy, and use (yes/no) of S-1 for second-line treatment as independent predictors for OS. This study concludes that second-line NFF therapy demonstrated a more favorable OS compared to S-1 therapy, however, it is still important to consider the patient background characteristics while selecting the most appropriate treatment.
Assuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Combinação de Medicamentos , Fluoruracila , Gencitabina , Irinotecano , Leucovorina , Oxaliplatina , Paclitaxel , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Masculino , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Irinotecano/administração & dosagem , Irinotecano/uso terapêutico , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Idoso , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Albuminas/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Estudos Retrospectivos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Adulto , Lipossomos , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Optimal adjuvant chemotherapy after laparoscopic surgery in gastric cancer (GC) patients is still undefined. We aimed to evaluate the efficacy of S-1 plus oxaliplatin (SOX) and capecitabine plus oxaliplatin (CAPOX) in patients with GC after laparoscopic gastrectomy. METHODS: A non-inferiority randomized controlled clinical trial was performed in China. Patients with advanced GC who underwent laparoscopic D2 gastrectomy were randomly assigned to receive SOX and CAPOX regimens. RESULTS: In total, 191 patients were screened between May 2018 and June 2019, and 140 (73.3%) were included in the modified intent-to-treat analysis (mITT), of whom 69 and 71 were assigned to the SOX and CAPOX groups, respectively. The SOX group had similar 3-year overall survival (OS) and disease-free survival to the CAPOX group. Subgroup analysis revealed significantly better OS in the SOX group for male patients ([HR] = 0.395; 95% [CI], 0.153-1.019; p = 0.045), age >60 (HR = 0.219; 95% [CI], 0.064-0.753; p = 0.016), tumors in the gastric antrum (HR = 0.273; 95% [CI], 0.076-0.981; p = 0.047), and moderately differentiated tumors (HR = 0.338; 95% [CI], 0.110-1.041; p = 0.041). There were no significant differences observed in terms of adverse events and recurrence patterns between the two groups. CONCLUSION: Adjuvant SOX was non-inferior to CAPOX treatments for patients with GC who underwent curative laparoscopic D2 gastrectomy. For male patients, aged >60 years, tumors in the gastric antrum, and moderately differentiated tumors, adjuvant SOX may achieve an improvement compared with CAPOX.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Combinação de Medicamentos , Gastrectomia , Laparoscopia , Oxaliplatina , Ácido Oxônico , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Masculino , Gastrectomia/métodos , Feminino , Pessoa de Meia-Idade , Laparoscopia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Tegafur/uso terapêutico , Tegafur/administração & dosagem , Ácido Oxônico/uso terapêutico , Ácido Oxônico/administração & dosagem , Quimioterapia Adjuvante/métodos , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Idoso , AdultoRESUMO
RATIONALE: Treatment strategies for rectal squamous cell carcinoma (rSCC) are yet to be established, given its rarity. Although squamous cell carcinoma has been reported to be highly sensitive to cetuximab and radiation, there is no report of combination therapy of cetuximab and radiation for rSCC. In this study, we firstly reported a case of rSCC in which a complete response was achieved with the original chemoradiotherapy comprising oxaliplatin, S-1, cetuximab, and simultaneous radiation. PATIENT CONCERNS: A 46-year-old women presented to our hospital with lower abdominal pain and fatigue. DIAGNOSES: Based on tumor marker analyses, histological examination of biopsy specimens, and comprehensive imaging, the patient was diagnosed with rSCC. INTERVENTIONS: Neoadjuvant chemoradiotherapy (50.4 Gy) was administered in 28 fractions, along with concurrent chemotherapy comprising SOX (S-1: 80 mg/m2, days 1-5 and 8-12, oxaliplatin: 85 mg/m2, day 1) and cetuximab (400 mg/m2, day 1, 250 mg/m2, after day 8). OUTCOMES: Five weeks after chemoradiation, the patient underwent laparoscopic partial intersphincteric resection, achieving a complete pathological response. LESSONS: This case firstly highlights the usefulness of SOX plus cetuximab combined with radiation in the treatment of locally advanced rSCC. However, a large-scale study is required to establish safe and effective treatment regimens.
Assuntos
Carcinoma de Células Escamosas , Cetuximab , Quimiorradioterapia , Fluoruracila , Terapia Neoadjuvante , Oxaliplatina , Neoplasias Retais , Humanos , Feminino , Cetuximab/uso terapêutico , Cetuximab/administração & dosagem , Pessoa de Meia-Idade , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/tratamento farmacológico , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Terapia Neoadjuvante/métodos , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Quimiorradioterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tegafur/uso terapêutico , Tegafur/administração & dosagem , Ácido Oxônico/uso terapêutico , Ácido Oxônico/administração & dosagem , Combinação de MedicamentosRESUMO
This study aimed to investigate the prognostic relationship between relative dose intensity (RDI) of adjuvant S-1 chemotherapy and psoas muscle mass volume (PMV) in patients with resected pancreatic ductal adenocarcinoma. We enrolled 105 patients with histologically confirmed pancreatic ductal adenocarcinoma who had undergone pancreatectomy. Adjuvant S-1 chemotherapy was administered to 72 (68.6%) of the 105 patients and not to the remaining 33 patients. Patients who received adjuvant S-1 chemotherapy were stratified into high- and low-RDI groups by the cutoff value for RDI. Five-year overall survival (OS) and relapse-free survival (RFS) rates were significantly higher in the high- than in the low-RDI group. Similarly, both the 5-year OS and RFS rates were significantly greater among patients in the high-PMV group than among patients in the low-PMV group. The RDI was an independent prognostic factor in our study patients. Furthermore, patients who received adjuvant S-1 chemotherapy were stratified into 3 groups: those with both high RDI and high-PMV, Group A; those with either high RDI or high PMV (but not both), Group B; and those with both low RDI and low-PMV, group C. There were statistically significant differences in 5-year OS and RFS between 3 patient groups (5-year overall survival: Pâ =â .023, 5-year relapse-free survival: Pâ =â .001). The area under the curve for the combination of RDI and PMV (0.674) was greater than that for RDI alone (0.645). A sufficient dosage of adjuvant S-1 chemotherapy is important in improving survival of patients with resected pancreatic ductal adenocarcinoma. A combination of RDI and PMV may predict the prognosis of patients with resected pancreatic ductal adenocarcinoma more effective than RDI alone.
Assuntos
Carcinoma Ductal Pancreático , Combinação de Medicamentos , Ácido Oxônico , Pancreatectomia , Neoplasias Pancreáticas , Músculos Psoas , Tegafur , Humanos , Masculino , Feminino , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Estudos Retrospectivos , Pessoa de Meia-Idade , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patologia , Músculos Psoas/patologia , Quimioterapia Adjuvante/métodos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Idoso , Pancreatectomia/métodos , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Prognóstico , Relação Dose-Resposta a Droga , AdultoAssuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Ductal Pancreático , Desoxicitidina , Combinação de Medicamentos , Gencitabina , Terapia Neoadjuvante , Ácido Oxônico , Paclitaxel , Neoplasias Pancreáticas , Tegafur , Humanos , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácido Oxônico/administração & dosagem , Tegafur/administração & dosagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Terapia Neoadjuvante/métodos , Albuminas/administração & dosagem , Taxa de Sobrevida , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgiaAssuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Ductal Pancreático , Desoxicitidina , Combinação de Medicamentos , Gencitabina , Terapia Neoadjuvante , Ácido Oxônico , Paclitaxel , Neoplasias Pancreáticas , Tegafur , Humanos , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Ácido Oxônico/administração & dosagem , Tegafur/administração & dosagem , Albuminas/administração & dosagem , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologiaRESUMO
AIM: We evaluated the efficacy of neoadjuvant chemotherapy with intensity-modulated radiotherapy (NAC-IMRT) in patients with borderline-resectable pancreatic cancer (BRPC). METHODS: BRPC patients were treated with IMRT (45 Gy/15fr) combined with two courses of S-1 (40 mg/m2 bid) before surgery. Outcomes after NAC-IMRT, surgery, and survival were then evaluated. This single-center retrospective study assessed 26 consecutive patients. RESULTS: Twenty-six patients (BR-PV: 7, BR-A: 19) with a median age of 73 years were enrolled from 2016 to 2021. Ten (38%) patients were 75-years-old and above. Twenty-three patients completed NAC-IMRT treatment. The median reductions in tumor size and cancer antigen 19-9 level were 13.6% and 69%, respectively. All 26 patients underwent resection within a median time of 71 days after NAC-IMRT initiation. R0 resection was achieved in 24 patients (92%). The median overall survival (OS) was 28.0 months, and the 1- and 3-year OS rates were 100% and 34%, respectively. The median progression-free survival (PFS) was 12.5 months, and the 1- and 3-year PFS rates were 50% and 32%, respectively. No significant differences were observed in OS between the patients under and over the age of 75 (29 vs. 20 months, p = 0.86). The 12 patients who completed NAC-IMRT, resection, and subsequent adjuvant chemotherapy (AC) exhibited a 3-year survival rate of 73%, which was significantly better than that of the patients who did not receive or complete AC (median OS, not reached vs. 19 months, p < 0.001). CONCLUSION: NAC-IMRT showed outstanding clinical efficacy with acceptable tolerability in patients with BRPC, including geriatric patients.
Assuntos
Combinação de Medicamentos , Terapia Neoadjuvante , Ácido Oxônico , Neoplasias Pancreáticas , Radioterapia de Intensidade Modulada , Tegafur , Humanos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Feminino , Masculino , Idoso , Ácido Oxônico/administração & dosagem , Tegafur/administração & dosagem , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Taxa de SobrevidaRESUMO
BACKGROUND: Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer. METHODS: This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer. RESULTS: MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group. CONCLUSIONS: The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors.
Assuntos
Gastrectomia , Instabilidade de Microssatélites , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Feminino , Masculino , Prognóstico , Idoso , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Tegafur/uso terapêutico , Adulto , Combinação de Medicamentos , Ácido Oxônico/uso terapêutico , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Taxa de Sobrevida , Mutação , Perfilação da Expressão Gênica , Sequenciamento do Exoma , Proteína 1 Homóloga a MutL/genética , Regulação Neoplásica da Expressão GênicaRESUMO
OBJECTIVE: This study aims to develop a nomogram integrating inflammation (NLR), Prognostic Nutritional Index (PNI), and EBV DNA (tumor burden) to achieve personalized treatment and prediction for stage IVA NPC. Furthermore, it endeavors to pinpoint specific subgroups that may derive significant benefits from S-1 adjuvant chemotherapy. METHODS: A total of 834 patients diagnosed with stage IVA NPC were enrolled in this study and randomly allocated into training and validation cohorts. Multivariate Cox analyses were conducted to identify independent prognostic factors for constructing the nomogram. The predictive and clinical utility of the nomogram was assessed through measures including the AUC, calibration curve, DCA, and C-indexes. IPTW was employed to balance baseline characteristics across the population. Kaplan-Meier analysis and log-rank tests were utilized to evaluate the prognostic value. RESULTS: In our study, we examined the clinical features of 557 individuals from the training cohort and 277 from the validation cohort. The median follow-up period was 50.1 and 49.7 months, respectively. For the overall cohort, the median follow-up duration was 53.8 months. The training and validation sets showed 3-year OS rates of 87.7% and 82.5%, respectively. Meanwhile, the 3-year DMFS rates were 95.9% and 84.3%, respectively. We created a nomogram that combined PNI, NRI, and EBV DNA, resulting in high prediction accuracy. Risk stratification demonstrated substantial variations in DMFS and OS between the high and low risk groups. Patients in the high-risk group benefited significantly from the IC + CCRT + S-1 treatment. In contrast, IC + CCRT demonstrated non-inferior 3-year DMFS and OS compared to IC + CCRT + S-1 in the low-risk population, indicating the possibility of reducing treatment intensity. CONCLUSIONS: In conclusion, our nomogram integrating NLR, PNI, and EBV DNA offers precise prognostication for stage IVA NPC. S-1 adjuvant chemotherapy provides notable benefits for high-risk patients, while treatment intensity reduction may be feasible for low-risk individuals.
Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Estadiamento de Neoplasias , Nomogramas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Quimioterapia Adjuvante/métodos , Prognóstico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Inflamação , Adulto , Avaliação Nutricional , Herpesvirus Humano 4/isolamento & purificação , Tegafur/uso terapêutico , Tegafur/administração & dosagem , DNA Viral , Combinação de Medicamentos , Ácido Oxônico/uso terapêutico , Ácido Oxônico/administração & dosagem , Idoso , Estimativa de Kaplan-MeierRESUMO
BACKGROUND AND PURPOSE: The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study. MATERIALS AND METHODS: This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients. RESULTS: Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs. INTERPRETATION: S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules.
Assuntos
Capecitabina , Cardiotoxicidade , Neoplasias Colorretais , Combinação de Medicamentos , Fluoruracila , Ácido Oxônico , Tegafur , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Tegafur/efeitos adversos , Tegafur/administração & dosagem , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Ácido Oxônico/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Cardiotoxicidade/etiologia , Capecitabina/efeitos adversos , Capecitabina/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Adulto , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Hand-foot syndrome (HFS) is a common side effect of fluoropyrimidine anticancer drugs and often becomes a dose-limiting manifestation of toxicity once it occurs. The precise mechanism of HFS remains unclear, and effective measures to prevent or relieve it are currently limited. To investigate the pathogenesis of HFS and effective measures for treating or preventing it, establishment of animal models is crucial. Here, we gave male SD rats 170 mg/kg of tegafur (prodrug of 5-FU) daily for 35 days and evaluated their clinical and histopathological characteristics and pain-related behavioral tests. TUNEL-positive apoptotic cells and 5-FU concentrations in the plantar skin were also evaluated to investigate the mode of toxicity. Tegafur treatment induced hypersensitivity to mechanical pressure on the plantar surface beginning in Week 3, with decreased locomotor activity. Focal desquamation of the plantar skin was observed almost concomitantly and gradually worsened to palmar and plantar skin thickening with severe desquamation, cracks, or both. Histopathological lesions in the plantar skin at treatment end included desquamation and thickening, with epidermal cell swelling and spongiosis and focal inflammation in the dermis. The time-course of development and the characteristics of the tegafur-induced skin lesions were highly similar to those in human fluoropyrimidine-induced HFS, indicating that a HFS rat model was successfully established. Localized high concentrations of 5-FU in the palmar and plantar skin, with increased apoptosis, are likely involved in the mode of toxicity. Our model should clarify the pathogenesis of HFS, providing new insights into the best supportive care and prevention.
Assuntos
Antimetabólitos Antineoplásicos , Modelos Animais de Doenças , Síndrome Mão-Pé , Ratos Sprague-Dawley , Tegafur , Animais , Masculino , Tegafur/toxicidade , Ratos , Síndrome Mão-Pé/etiologia , Antimetabólitos Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/patologiaRESUMO
BACKGROUND: In gastric cancer, peritoneal metastasis is the most common form of metastasis and leads to dismal prognosis. We aimed to evaluate the safety and efficacy of combining perioperative intraperitoneal (IP) plus systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer with limited peritoneal metastasis or even after reducing peritoneal tumor burden by upfront IP chemotherapy. METHOD: Patients were enrolled in phase Ib in a 3 + 3 dose escalation of IP paclitaxel plus a fixed dose of IP cisplatin and oral S-1. In phase II, patients were managed according to the peritoneal cancer index (PCI) by diagnostic laparoscopy. For patients with a PCI of >12, upfront IP and systemic chemotherapy were given. Patients with a PCI of ≤12 or reduced to ≤12 after upfront chemotherapy underwent CRS with HIPEC. The primary endpoints were safety and the recommended phase II dose (RP2D) confirmation for phase Ib and the 1-year overall survival rate for phase II. RESULTS: The RP2D was defined as IP 175 mg/m2 paclitaxel and 60 mg/m2 cisplatin and oral 70 mg/m2/day S-1 for 14 days. A total of 22 patients were included. After CRS with HIPEC, there were no grade 3 or higher complications. The median hospital stay was 7 days (range, 6-11). The median overall and progression-free survival were 27.3 months (95% CI, 14.4 to not estimable) and 12.6 months (95% CI, 7.7-14.5), respectively. One-year overall and progression-free survival rates were 81.0% (95% CI, 65.8-99.6) and 54.5% (95% CI, 37.2-79.9), respectively. CONCLUSION: A combination of IP plus systemic chemotherapy, CRS, and HIPEC was safe and resulted in good survival outcomes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Paclitaxel , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Quimioterapia Intraperitoneal Hipertérmica/métodos , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/mortalidade , Cisplatino/administração & dosagem , Paclitaxel/administração & dosagem , Idoso , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Adulto , Tegafur/administração & dosagem , Ácido Oxônico/administração & dosagem , Combinação de Medicamentos , Terapia Combinada , Taxa de SobrevidaRESUMO
BACKGROUND: Advanced gastric cancer (AGC) that does not respond to first-line therapy poses a challenge to clinical management. The objective of this study was to compare the efficacy and safety of apatinib combined with S-1 in second-line and above treatment of AGC. METHODS: Cochrane Library, Science Direct, EMBASE, PubMed, and CNKI were searched for randomized controlled trial until August 2023. Only patients who met "Standardized Diagnosis and Treatment Guide for Gastric Cancer" were included in the study. The accurate data and distinguishing between follow-up time and drug dose were extracted to reduce heterogeneity and the risk of bias of the included trials was evaluated according to the Cochrane Handbook. Finally, the survival benefit of the treatment was evaluated based on clinical response rate, survival period, biochemical index, and adverse event occurrence in the trial. RESULTS: The meta-analysis included 29 randomized controlled trials involving 2149 participants. Statistically significant increases in clinical effective rate (odds ratiosâ =â 2.61, 95% confidence interval [2.13-3.20], Pâ <â .00001) and disease control rate (odds ratiosâ =â 3.16, 95% confidence interval [2.54-3.94], Pâ <â .00001) were found when apatinib combined with S-1, and also had obvious advantages in reducing tumor markers and regulating immune factors. In addition, apatinib combined with S-1 significantly increased the risk of hypertension but reduced damage to liver function, while the improvement of other adverse events was not pronounced. DISCUSSION: Apatinib combined with S-1 is more effective and safe for second-line and above treatment of AGC. This study minimized the conclusion bias caused by the basic data sources, but more high-quality studies are still needed to validate these conclusions.
Assuntos
Combinação de Medicamentos , Ácido Oxônico , Piridinas , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/tratamento farmacológico , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Ácido Oxônico/efeitos adversos , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Tegafur/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Resultado do TratamentoAssuntos
Combinação de Medicamentos , Ácido Oxônico , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Quimioterapia Adjuvante , Seguimentos , Estadiamento de Neoplasias , Antimetabólitos Antineoplásicos/uso terapêutico , Estudos de Equivalência como AsuntoRESUMO
INTRODUCTION: S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase I/II study to evaluate the feasibility, tolerability, and efficacy of administering S-1 in the adjuvant setting after R0-resection of adenocarcinoma of the stomach and esophagogastric junction (EGJ) in Caucasian patients. METHODS: In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment. One treatment cycle consisted of oral S-1 (30 mg/m2 bid) for 14 days. Cycles were repeated every 3 weeks for 18 cycles (54 weeks). Primary endpoint was feasibility and tolerability. Safety was evaluated according to the Common Toxicity Criteria Adverse Events (CTCAE) version 4.0. Secondary endpoints were 1-year relapse-free survival (RFS) rate, RFS, and overall survival (OS). RESULTS: Between October 2015 and February 2018, 32 patients were enrolled in 12 German centers, and 30 started adjuvant study treatment. Seventeen patients completed all 18 cycles. Two patients terminated study treatment early due to adverse events (AEs), 7 due to patient's or investigator's decision, and 4 due to recurrence or distant metastasis during adjuvant therapy. Dose levels were reduced to 25 mg/m2 in 9 patients and to 20 mg/m2 in 1 patient. Of patients completing all 18 cycles, 5 did so with reduced dosage of S-1. Documented grade ≥3 AEs were neutropenia, diarrhea, vomiting, polyneuropathy, palmar-plantar erythrodysaesthesia, and rash. Serious AEs were observed in 7 patients. Median RFS was 32.2 months. One-year RFS rate was 77%. Data on OS were still premature at the end of the study. CONCLUSION: Adjuvant treatment with S-1 for 1 year is a feasible and safe treatment option for Caucasian patients diagnosed with gastric adenocarcinoma or cancer of the EGJ after R0-resection.