RESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Combinación de Medicamentos , Gastrectomía , Oxaliplatino , Ácido Oxónico , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Masculino , Femenino , Tegafur/administración & dosificación , Tegafur/efectos adversos , Tegafur/uso terapéutico , Persona de Mediana Edad , Oxaliplatino/administración & dosificación , Oxaliplatino/uso terapéutico , Estudios Retrospectivos , Gastrectomía/métodos , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Ácido Oxónico/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Quimioterapia Adyuvante/métodos , Paclitaxel Unido a Albúmina/administración & dosificación , Paclitaxel Unido a Albúmina/uso terapéutico , Adulto , Supervivencia sin Enfermedad , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Albúminas/administración & dosificaciónRESUMEN
OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients. METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.
Asunto(s)
Neoplasias de la Mama , Receptor ErbB-2 , Trastuzumab , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Trastuzumab/uso terapéutico , Trastuzumab/farmacología , Estudios Prospectivos , Anciano , Receptor ErbB-2/metabolismo , Paclitaxel Unido a Albúmina/uso terapéutico , Paclitaxel Unido a Albúmina/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Acrilamidas/uso terapéutico , Terapia Neoadyuvante/métodos , Proto-Oncogenes Mas , Ácidos Sulfínicos/uso terapéutico , Ácidos Sulfínicos/farmacología , Aminoquinolinas/uso terapéutico , Aminoquinolinas/farmacología , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the short-term safety of albumin-bound paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) during and after gastric cancer (GC) surgery. METHODS: A retrospective analysis of clinical data was conducted for GC surgery patients at Zhongnan Hospital of Wuhan University, from January 2020 to September 2022. The study group (n = 120) received HIPEC and the control group (n = 268) did not receive albumin-bound paclitaxel. Short-term safety indicators including intraoperative complications, hematological toxicity, liver and kidney function, and gastrointestinal function recovery were compared between the two groups. RESULTS: There were no statistically significant differences between the two groups regarding intraoperative complications, hematological toxicity, liver and kidney function, and gastrointestinal function recovery time (P > 0.05 for all). In the study group, patients were further divided into subgroups based on dose and timing. Subgroup analysis revealed no significant differences among the different dose subgroups. However, when focusing on timing subgroups, the postoperative subgroup exhibited significantly higher white blood cell counts and bilirubin levels compared to the intraoperative subgroup, while the intraoperative subgroup had significantly higher bilirubin levels compared to both postoperative and intraoperative plus postoperative subgroups. CONCLUSION: Albumin-bound paclitaxel demonstrates good safety and tolerability in HIPEC during and after GC surgery, without increasing the risk of intraoperative complications.
Asunto(s)
Paclitaxel Unido a Albúmina , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Masculino , Quimioterapia Intraperitoneal Hipertérmica/métodos , Quimioterapia Intraperitoneal Hipertérmica/efectos adversos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Paclitaxel Unido a Albúmina/administración & dosificación , Paclitaxel Unido a Albúmina/uso terapéutico , Anciano , Adulto , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos Fitogénicos/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversosRESUMEN
INTRODUCTION: Recent studies have suggested enhanced therapeutic effects of subsequent chemotherapy after immune checkpoint inhibitor (ICI) treatment, highlighting the importance of subsequent treatment selection. Nanoparticle albumin-bound paclitaxel (nab-PTX) is commonly used in subsequent chemotherapies; however, its efficacy as a subsequent treatment after ICI treatment has not been reported. METHODS: We retrospectively evaluated the efficacy and safety of nab-PTX using two prospective studies that we previously reported. The first study evaluated the efficacy and safety of nab-PTX as a second-line treatment after the failure of the first-line cytotoxic chemotherapy, excluding ICI (study 1; n = 32), and the other as a subsequent treatment after failure of ICI treatment, regardless of treatment line (study 2; n = 29). RESULTS: The objective response rate was significantly higher in study 2 {55.2% (95% confidence interval [CI]: 28.1-79.6)} than in study 1 (28.1% [95% CI: 13.7-46.7]) (p = 0.04). Although the disease control rate was slightly higher in study 2 (86.2% [95% CI: 65.9-97.0]) than in study 1 (71.9% [95% CI: 53.3-86.3]), there was no significant difference (p = 0.2). The median progression-free survival was significantly longer in study 2 than in study 1 (3.9 months [95% CI: 2.0-5.5] in study 1 vs. 5.6 months [95% CI: 3.0-12.8] in study 2; hazard ratio [HR]: 0.46 [95% CI: 0.27-0.81], p = 0.006). The median overall survival was slightly longer in study 2 despite the greater number of patients who received nab-PTX in late treatment line, but there was no significant difference between study 1 and study 2 (10.9 months [95% CI: 5.1-16.8] in study 1 vs. 11.9 months [95% CI: 7.6-24.8] in study 2; HR: 0.77 [95% CI: 0.46-1.31], p = 0.34). Safety profiles did not differ between the patients in studies 1 and 2. CONCLUSION: Nab-PTX monotherapy may be an effective subsequent treatment option after ICI treatment.
Asunto(s)
Albúminas , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Masculino , Anciano , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Albúminas/uso terapéutico , Albúminas/administración & dosificación , Estudios Retrospectivos , Estudios Prospectivos , Paclitaxel Unido a Albúmina/uso terapéutico , Estudios de Seguimiento , Anciano de 80 o más Años , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Adulto , Nanopartículas/uso terapéutico , Resultado del TratamientoRESUMEN
Objective: This research aimed to assess the efficacy and safety of pembrolizumab (PBL) combined with albumin-bound paclitaxel (ab-Pac) and nedaplatin (NDP) for advanced esophageal squamous cell carcinoma (ESCC). Methods: A total of 47 ESCC patients were administered PBL or NDP on day 1 and ab-Pac on days 1 and 8, every 21 days for one cycle. Tumor and toxicities were evaluated every two cycles and every cycle, respectively. Results: The objective response rate was 68.1% and the disease control rate was 100%. The median follow-up was 16.7 months; median progression-free and overall survival were 12.6 and 19.9 months, respectively. Conclusion: The combination of PBL with ab-Pac and NDP proved to be an effective and safe treatment regimen for advanced ESCC.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Compuestos Organoplatinos , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Paclitaxel Unido a Albúmina/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Resultado del Tratamiento , Paclitaxel/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Taxanes are the basic components of breast cancer chemotherapy. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) shows improved antitumor effects because of more targeted delivery. However, the effects of nab-paclitaxel have not been systematically studied in patients with metastatic breast cancer (MBC) pretreated with taxanes. Considering the limited treatment options for MBC, this study retrospectively evaluated the clinical efficacy and adverse effects of nab-paclitaxel in patients with taxane-pretreated MBC. METHODS: Patients who had previously received taxanes and subsequently received nab-paclitaxel chemotherapy for MBC at Jiangsu Cancer Hospital between October 2014 and April 2022 were included for analysis. The primary end point was progression-free survival (PFS), and the secondary end points were the objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and side effects. RESULTS: A total of 236 female patients with MBC were included. The median PFS was 7.20 months (95% confidence interval [CI], 6.63-7.80 months), and the ORR, DCR, and CBR were 29.55% (95% CI, 23.50%-35.60%), 83.64% (95% CI, 78.70%-88.60%), and 56.36% (95% CI, 49.80%-63.00%), respectively. Following nab-paclitaxel treatment, the median PFS of patients who were sensitive to taxanes during previous treatments was significantly longer than that of patients who were resistant to taxanes (7.57 months vs. 4.43 months, p < .001). The most common adverse events were sensory neuropathy (89.83%), neutropenia (48.73%), leukopenia (46.61%), and anemia (35.59%). CONCLUSION: Nab-paclitaxel demonstrated clinical activity in taxane-pretreated patients with MBC. This beneficial effect was observed both in patients who were sensitive and resistant to taxanes during previous treatments. These results suggest nab-paclitaxel as the preferred chemotherapy regimen in patients with MBC, regardless of their sensitivity to taxanes during previous treatments.
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Neoplasias de la Mama , Hidrocarburos Aromáticos con Puentes , Nanopartículas , Neutropenia , Humanos , Femenino , Neoplasias de la Mama/patología , Paclitaxel Unido a Albúmina/uso terapéutico , Estudios Retrospectivos , Paclitaxel , Taxoides/efectos adversos , Albúminas/efectos adversos , Neutropenia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
BACKGROUND: Temozolomide (TMZ) treatment efficacy in glioblastoma (GBM) patients has been limited by resistance in the clinic. Currently, there are no clinically proven therapeutic options available to restore TMZ treatment sensitivity. Here, we investigated the potential of albumin-bound paclitaxel (ABX), a novel microtubule targeting agent, in sensitizing GBM cells to TMZ and elucidated its underlying molecular mechanism. METHODS: A series of in vivo and in vitro experiments based on two GBM cell lines and two primary GBM cells were designed to evaluate the efficacy of ABX in sensitizing GBM cells to TMZ. Further proteomic analysis and validation experiments were performed to explore the underlying molecular mechanism. Finally, the efficacy and mechanism were validated in GBM patients derived organoids (PDOs) models. RESULTS: ABX exhibited a synergistic inhibitory effect on GBM cells when combined with TMZ in vitro. Combination treatment of TMZ and ABX was highly effective in suppressing GBM progression and significantly prolonged the survival oforthotopic xenograft nude mice, with negligible side effects. Further proteomic analysis and experimental validation demonstrated that the combined treatment of ABX and TMZ can induce sustained DNA damage by disrupting XPC and ERCC1 expression and nuclear localization. Additionally, the combination treatment can enhance ferroptosis through regulating HOXM1 and GPX4 expression. Preclinical drug-sensitivity testing based on GBM PDOs models confirmed that combination therapy was significantly more effective than conventional TMZ monotherapy. CONCLUSION: Our findings suggest that ABX has the potential to enhance TMZ treatment sensitivity in GBM, which provides a promising therapeutic strategy for GBM patients.
Asunto(s)
Neoplasias Encefálicas , Ferroptosis , Glioblastoma , Animales , Ratones , Humanos , Temozolomida/farmacología , Temozolomida/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Paclitaxel Unido a Albúmina/farmacología , Paclitaxel Unido a Albúmina/uso terapéutico , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Alquilantes/uso terapéutico , Ratones Desnudos , Proteómica , Resistencia a Antineoplásicos , Daño del ADN , Línea Celular Tumoral , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
PURPOSE: There are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study aims to retrospectively evaluate the efficacy of different taxanes on neoadjuvant systemic treatment (NST) in breast cancer. METHODS: Patients who were diagnosed with breast cancer and had received integral NST from August 2013 to April 2022 were enrolled. The efficacy was divided into total pathological complete response (total-pCR), breast pathological complete response (breast-pCR), and axillary pathological complete response (axillary-pCR) for in-depth analysis and discussion. RESULTS: The choice of taxane was an independent risk factor for total-pCR and breast-pCR rates. The highest total-pCR and breast-pCR rates were found in the Nab-P group. The difference was not significant among all the taxanes in the axillary-pCR rate. CONCLUSION: Nab-P significantly improved the total-pCR and breast-pCR rates. It should be the first choice among taxanes in NST for breast cancer.
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Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Docetaxel/uso terapéutico , Paclitaxel Unido a Albúmina/uso terapéutico , Terapia Neoadyuvante , Estudios Retrospectivos , Paclitaxel/uso terapéutico , Albúminas , Taxoides/uso terapéutico , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMEN
To investigate the impact of Xihuang Capsule combined with albumin-bound paclitaxel on the treatment of stage III breast cancer and T cell subsets, survival rate and adverse reactions. Totally 200 patients with stage III breast cancer were evenly randomized into control group (albumin-bound paclitaxel for chemotherapy) and observation group (Xihuang Capsules for adjuvant therapy based on the treatment of the control group). The RR and DCR of the observation group was markedly higher as compared to the control group (66.7% vs 28.6%; 80.9% VS 47.6%) (all P <0.05). After 4 weeks of treatment, the CD8+ in the two groups decreased, while CD3+ and CD4+ increased, and the change in observation group was more significant (all P<0.05). The observation group exhibited a better half-year, 1-year, 1.5-year and 2-year survival rates compared to the control group (81.0% vs 71.4%, 71.4% vs 57.1%, 57.1% vs 33.3% and 42.9%vs 19.0%) (all P<0.05). Adding Xihuang Capsule to adjuvant therapy with albumin paclitaxel chemotherapy benefits the patient's immunity and survival rate, with good efficacy and safety profiles.
Asunto(s)
Paclitaxel Unido a Albúmina , Neoplasias de la Mama , Humanos , Femenino , Paclitaxel Unido a Albúmina/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Tasa de Supervivencia , Paclitaxel/efectos adversos , Albúminas/efectos adversos , Subgrupos de Linfocitos T , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
OBJECTIVE: Dose-dense chemotherapy has shown a better prognosis than standard interval chemotherapy in adjuvant settings for high-risk breast cancer. This study aimed to evaluate the efficacy and safety of dose-dense nanoparticle albumin-bound paclitaxel followed by dose-dense epirubicin and cyclophosphamide as neoadjuvant chemotherapy for human epidermal growth factor 2 (HER2)-negative operable breast cancer. METHODS: Patients with histologically confirmed stage I-III HER2-negative breast cancer were enrolled in this study. Patients received nanoparticle albumin-bound paclitaxel (260 mg/m2) followed by epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 2 weeks with pegfilgrastim. The primary endpoint was the pathological complete response rate. Patients also underwent prophylactic management for peripheral neuropathy, which involved a combination of cryotherapy, compression therapy using elastic stockings and medications including goshajinkigan. RESULTS: Among the 55 patients enrolled in this study, 13 (23.6%) achieved pathological complete response, of whom 10/26 (38.5%) patients had triple-negative disease and 3/29 (10.3%) had luminal disease. The objective response was observed in 46 (83.6%) patients. Of the 36 patients who were initially planned for mastectomy, 11 (30.6%) underwent breast-conserving surgery after neoadjuvant chemotherapy. The most common grade 3-4 adverse events were myalgia (14.5%), fatigue (12.7%) and elevated transaminase levels (9.1%). No patients experienced febrile neutropenia. Eight (14.5%) patients discontinued treatments due to adverse events. CONCLUSIONS: Neoadjuvant dose-dense biweekly nanoparticle albumin-bound paclitaxel followed by dose-dense epirubicin and cyclophosphamide was effective, especially in patients with triple-negative disease, and feasible with pegfilgrastim support.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Epirrubicina/efectos adversos , Terapia Neoadyuvante , Paclitaxel Unido a Albúmina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Mastectomía , Paclitaxel/efectos adversos , Ciclofosfamida/efectos adversos , Resultado del TratamientoRESUMEN
There is substantial evidence that albumin-bound paclitaxel (nab-paclitaxel) is effective and safe for the treatment of breast, lung and pancreatic cancers. However, it can still cause adverse effects by affecting cardiac enzymes, hepatic enzyme metabolism and blood routine related indicators, which affects the use of chemotherapy for a full course of treatment. However, there are no relevant clinical studies to systematically observe the effects and dynamics of albumin-bound paclitaxel on cardiac enzymes, liver enzyme metabolism, and routine blood-related indices. The purpose of our study was to determine the levels of serum creatinine (Cre), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), white blood cells (WBC) and hemoglobin (HGB) in cancer patients treated with albumin-conjugated paclitaxel. This study retrospectively analyzed 113 patients with cancer. Patients who had received two cycles of nab-paclitaxel 260 mg/m2 (administered intravenously on days 1, 8, and 15 of each 28-day cycle) were selected. Serum Cre, AST, ALT, LDH, CK, and CK-MB activities, WBC counts, and HGB levels were measured before and after treatment with two cycles. Fourteen cancer types were analyzed. The distribution of cancer types in patients was mainly concentrated in lung, ovarian, and breast cancer. Nab-paclitaxel treatment markedly decreased Cre, AST, LDH, and CK activities in the serum and WBC counts and HGB levels, respectively. Serum Cre and CK activities and HGB levels were remarkably downregulated at baseline compared to healthy controls. Patients receiving nab-paclitaxel treatment cause metabolic disorders in tumor patients by reducing the decrease of Cre, AST, LDH, CK, CK-MB, WBC and HGB indexes, thus inducing the occurrence of cardiovascular events, hepatotoxic events and fatigue and other symptoms. Therefore, for tumor patients, although receiving nab-paclitaxel improves the anti-tumor effect, it is still necessary to closely monitor the changes of related enzymatic and routine blood indicators, so as to detect and intervene at an early stage.
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Paclitaxel Unido a Albúmina , Neoplasias de la Mama , Humanos , Femenino , Paclitaxel Unido a Albúmina/uso terapéutico , Estudios Retrospectivos , Paclitaxel/efectos adversos , Albúminas/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Creatina Quinasa , Forma MB de la Creatina-QuinasaRESUMEN
OBJECTIVES: The advent of effective chemotherapy regimens has increased the use of neoadjuvant multiagent chemotherapy in pancreatic cancer. However, the effect of tumor downstaging with neoadjuvant treatment on survival is unclear. METHODS: Retrospective study included all resected patients with pancreatic adenocarcinoma who underwent neoadjuvant chemotherapy with FOLFIRINOX or gemcitabine/Abraxane. Downstaging was quantified using (1) difference between presenting AJCC clinical and final pathologic stage and (2) College of American Pathologists (CAP) Tumor Regression Grading Schema. RESULTS: Eighty-seven patients met inclusion criteria. FOLFIRINOX was the most common regimen, 63.2% vs 21.8%. Change in regimen occurred in 15% of patients. Downstaging based on a difference in AJCC stage group occurred in only 4.6%. In contrast, 45.2% were classified as downstaged by the CAP Tumor Regression of 0-2. Downstaging was similar for FOLFIRINOX gemcitabine/Abraxane (64.7 vs 53.6, P = .12) using the CAP criteria. On univariate analysis, treatment regimen (gemcitabine/Abraxane vs FOLFIRINOX, median survival 27 vs 29 mo; HR 1.57, P = .2) had similar survival. Downstaging by the AJCC stage was not associated with improved survival (HR 1.51, P = .4). However, there was a survival benefit for those downstaged by the CAP Tumor Regression Grading Schema, the median survival of 41 mo vs 25 mo; HR 3.05, P = .009. Improved survival 3.32 (1.35-8.16), P = .009) was maintained on multivariate analysis. CONCLUSION: Survival is significantly improved in those downstaged, as assessed by the CAP Tumor Regression Schema. Downstaging is an important prognostic variable that can help with joint decision making for clinicians and patients.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Paclitaxel Unido a Albúmina/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Estudios Retrospectivos , Estadificación de Neoplasias , Fluorouracilo/uso terapéutico , Gemcitabina , Terapia Neoadyuvante , Neoplasias PancreáticasRESUMEN
Breast cancer is the most common malignant tumor of women, which seriously threatens women's health. Albumin-bound paclitaxel is the basic chemotherapy drug for breast cancer treatment. We can promote reasonable clinical medication and improve patients' quality of life by standardizing chemotherapy plans, rationally optimizing treatment strategy and managing adverse reactions of albumin-bound paclitaxel. In order to standardize the clinical application of albumin-bound paclitaxel in breast cancer, Chinese Medical Doctor Association Oncologist Branch Breast Cancer Group and International Medical Exchange Branch of China Anti-Cancer Association consulted guidelines and the latest evidence-based evidences and formulated Chinese expert consensus of albumin-bound paclitaxel in the treatment of breast cancer to provide reference for clinical diagnosis and treatment of breast cancer. The consensus mainly introduces the clinical application strategies and evidence-based evidences of albumin-bound paclitaxel in advanced therapy, neoadjuvant therapy and adjuvant therapy of breast cancer. Among them, the regimens containing albumin-bound paclitaxel are the better recommended regimens for preoperative neoadjuvant and advanced rescue therapy of breast cancer. However, there is little evidence in adjuvant therapy, so it is recommended to use albumin-bound paclitaxel cautiously. We also invited breast cancer clinical experts to vote on some controversial issues, including but not limited to the usage and dosage of albumin-bound paclitaxel, combined medication and management of peripheral neuropathy, and formed consensus recommendations for the reference of breast cancer clinical workers.
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Paclitaxel Unido a Albúmina , Neoplasias de la Mama , Femenino , Humanos , Paclitaxel Unido a Albúmina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Consenso , Pueblos del Este de Asia , Calidad de VidaRESUMEN
This study was designed to observe the efficacy and safety of albumin-bound paclitaxel plus nedaplatin as neoadjuvant therapy in patients with esophageal squamous cell carcinoma (ESCC). From April 2019 to Dec 2020, patients with ESCC who underwent Mckeown surgery at our center were analyzed retrospectively. All patient received 2 to 3 cycles of albumin-bound paclitaxel combined with nedaplatin before surgery, tumor regression grade (TRG) and American National Cancer Institute Common Toxicity Criteria version 5.0 were used to evaluate its efficacy and safety. TRG grades from TRG 2 to TRG 5are considered effective in chemotherapy, TRG 1 stands for pathological complete response (pCR). A total of 41 patients were included in this study. All patients achieved R0 resection. According to the TRG classification, the number of patients assessed for TRG 1-TRG 5 were: 7 cases, 12 cases, 3 case, 12 cases and 7 cases. Its objective response rate and pCR were 82.9% (34/41) and 17.1% (7/41), respectively. We found that hematological toxicity is the most common adverse events of this regimen, with an incidence of 24.4%, followed by digestive tract reactions, with an incidence of 17.1%. Hair loss, neurotoxicity and hepatological disorder are the others, their incidence was 12.2%, 7.3%, and 2.4%; and chemotherapy related deaths were no found. Notably, 7 patients achieved pCR without recurrence or death. Survival analysis showed that patients with pCR may have longer disease-free survival (P = .085) and overall survival (P = .273), although the difference was not statistically significant. As neoadjuvant therapy for patients with ESCC, albumin-bound paclitaxel combined with nedaplatin has a higher pCR rate and less side effects. It is a reliable choice for ESCC patients as neoadjuvant therapy.
Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Paclitaxel Unido a Albúmina/uso terapéutico , Terapia Neoadyuvante , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
This study aimed to compare the efficacy of neoadjuvant systemic therapy (NST) with solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel in human epidermal growth factor receptor 2 (HER2)-low-positive and HER2-zero breast cancers. A total of 430 patients receiving 2-weekly dose-dense epirubicin and cyclophosphamide (EC) followed by 2-weekly paclitaxel (Sb-P, Lps-P, or Nab-P), or 3-weekly EC followed by 3-weekly docetaxel for NST were enrolled in the study. In HER2-low-positive patients, the pathological complete response (pCR) rate in Nab-P group was significantly higher than that in the other three paclitaxel groups (2.8 % in Sb-P group, 4.7 % in Lps-P group, 23.2 % in Nab-P group and 3.2 % in docetaxel group, p < 0.001). In HER2-zero patients, the pCR rate did not differ significantly among the four paclitaxel groups (p = 0.278). The NST regimen containing Nab-P could be considered a promising treatment option in HER2-low-positive breast cancer.
Asunto(s)
Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Neoplasias de la Mama/patología , Paclitaxel Unido a Albúmina/uso terapéutico , Terapia Neoadyuvante , Docetaxel/uso terapéutico , Lipopolisacáridos , Ciclofosfamida/uso terapéutico , Epirrubicina/uso terapéutico , Paclitaxel/uso terapéutico , Albúminas , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del TratamientoRESUMEN
Objective The effect of sarcopenia on the prognosis of patients undergoing chemotherapy for unresectable pancreatic ductal adenocarcinoma remains largely unexplored. In this retrospective study, we investigated the relationship between sarcopenia and the prognosis of patients receiving first-line nanoparticle albumin-bound paclitaxel plus gemcitabine for unresectable pancreatic ductal adenocarcinoma. Methods We enrolled 251 patients with unresectable metastatic or locally advanced pancreatic ductal adenocarcinoma who had received chemotherapy between January 2015 and December 2020 at Kitasato University Hospital. Univariate and multivariate analyses were performed using the stratified Cox proportional hazards model to determine variables significantly associated with the progression-free and overall survival. Propensity score matching was performed to mitigate selection bias effects. Results In the propensity score-matched cohort, the progression-free and overall survival were not significantly different between the sarcopenia and non-sarcopenia groups (p=0.335, and 0.679 respectively). The skeletal muscle index decreased by 4.4% and 6.5% in the sarcopenia and non-sarcopenia groups, respectively, during the early treatment phase (p=0.084). There were no significant differences between groups with regard to major adverse events or drug toxicity occurrences. Both the progression-free and overall survival were significantly shorter in the skeletal muscle index loss group than in the non-skeletal muscle index loss group (p=0.026 and 0.045, respectively). Conclusion Skeletal muscle index loss during the initial treatment phase may be an early marker for the long-term prognosis of patients receiving nanoparticle albumin-bound paclitaxel plus gemcitabine as first-line treatment for unresectable pancreatic ductal adenocarcinoma.
Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Sarcopenia , Humanos , Desoxicitidina/efectos adversos , Sarcopenia/etiología , Estudios Retrospectivos , Paclitaxel Unido a Albúmina/uso terapéutico , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/tratamiento farmacológico , Carcinoma Ductal Pancreático/complicaciones , Carcinoma Ductal Pancreático/tratamiento farmacológico , Gemcitabina , Pronóstico , Paclitaxel/efectos adversos , Albúminas/uso terapéutico , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias PancreáticasRESUMEN
Over the past decade, the dose of nanoparticles given to solid tumors has remained at a median of 0.7% of the injected dose. Most nanoparticles are trapped in a mononuclear phagocyte system (MPS), of which 85% are Kupffer cells. In our study, threshold doses of bovine serum albumin (BSA) nanoparticles were investigated for the uptake of Kupffer cells in vitro and in vivo. The antitumor effect and safety of albumin-bound paclitaxel (ABP) were improved by using threshold doses of BSA nanoparticles. We found a threshold dose of 20,000 nanoparticles per macrophage uptake in vitro and a saturation dose of 0.3 trillion nanoparticles in tumor-bearing mice. In vivo efficacy and safety evaluations demonstrated that the threshold doses of blank BSA nanoparticles could significantly improve the efficacy and safety of ABP against tumors compared with ABP alone. In this study, the delivery efficiency of ABP was improved by using blank nanoparticles to saturate Kupffer cells, which provided a new approach to studying the Kupffer cell saturation threshold and thus a new scheme for improving the curative effect of ABP.
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Nanopartículas , Neoplasias , Ratones , Animales , Albúmina Sérica Bovina , Macrófagos del Hígado , Portadores de Fármacos/uso terapéutico , Neoplasias/tratamiento farmacológico , Paclitaxel Unido a Albúmina/uso terapéuticoRESUMEN
The disorganized vasculatures in tumors represent a substantial challenge of intratumor nanomedicine delivery to exert the anticancer effects. Herein, we rationally designed a glutathione (GSH)-activated nitric oxide (NO) donor loaded bioinspired lipoprotein system (NO-BLP) to normalize tumor vessels and then promote the delivery efficiency of sequential albumin-bound paclitaxel nanoparticles (PAN) in tumors. NO-BLP exhibited higher tumor accumulation and deeper penetration versus the counterpart liposomal formulation (NO-Lipo) in 4T1 breast cancer tumors, thus producing notable vascular normalization efficacy and causing a 2.33-fold increase of PAN accumulation. The sequential strategy of NO-BLP plus PAN resulted in an 81.03% inhibition of tumor growth in 4T1 tumors, which was better than the NO-BLP monotherapy, PAN monotherapy, and the counterpart NO-Lipo plus PAN treatment. Therefore, the bioinspired lipoprotein of NO-BLP provides an encouraging platform to normalize tumor vessels and promote intratumor delivery of nanomedicines for effective cancer treatment.
Asunto(s)
Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Paclitaxel Unido a Albúmina/uso terapéutico , Óxido Nítrico , Sistemas de Liberación de Medicamentos/métodos , Paclitaxel , Neoplasias de la Mama/tratamiento farmacológico , Lipoproteínas/uso terapéutico , Nanopartículas/uso terapéutico , Línea Celular TumoralRESUMEN
Cerium oxide nanoparticles (CeONPs) displayed cytotoxic properties against some cancer cells. However, there is very limited data about the possible antitumoral potential of them in breast cancer cells when used alone and/or together with a chemotherapeutic drug. We investigated the effects of CeONPs alone or in combination with paclitaxel (PAC) on healthy or carcinoma breast cells. After human breast cancer cells (MCF-7) treated with CeONPs alone or together with PAC for 24, 48, and 72 h, the effects of CeONPs on cell viability, apoptosis, migration, and adhesion were investigated. All cell viability and IC50 values of CeONPs and PAC treatments in healthy breast cells (HTERT-HME1) were higher than MCF-7 cells. They showed higher cytotoxicity against MCF-7 cells. CeONPs (10, 20, and 30 mM) and/or abraxane (AB) (2 µM) significantly decreased cell viability values in MCF-7 cells. All CeONPs concentrations increased the number of apoptotic MCF-7 cells. CeONPs (20 and 30 mM) alone or in combination with AB for 72 h treatment also significantly increased the apoptosis in compared to AB alone. CeONPs and/or AB can significantly inhibit the migratory ability of breast cancer cells. The migration rates in co-treated groups with CeONPs and AB were lower than CeONPs treatments. Higher concentrations of CeONPs alone or together with AB inhibited cell adhesion. Our results showed CeONPs can increase cytotoxicity and apoptosis and decrease cell migration and cell adhesion when used alone or together with AB. Therefore, combination of chemotherapeutics with CeONPs may provide a good strategy against cancer.