RESUMO
The optimal treatment of burn shock is still unresolved. The problem of "fluid creep" continues despite modern devices that fail to improve outcomes over hourly urine output. Colloids, especially albumin, reduce fluid requirements. Albumin can be used either immediately at the start of resuscitation, or as a "rescue" when crystalloid use is excessive. Several studies confirm that when crystalloid resuscitation is "out of control" the majority of caregivers will add albumin to reduce fluid rates. A multi-center trial is underway comparing crystalloids with albumin to confirm the benefit of colloids. The next question is whether albumin or plasma is as the better colloid choice.
Assuntos
Albuminas , Queimaduras , Hidratação , Ressuscitação , Humanos , Queimaduras/terapia , Ressuscitação/métodos , Hidratação/métodos , Albuminas/uso terapêutico , Albuminas/administração & dosagem , Soluções Cristaloides/administração & dosagem , Soluções Cristaloides/uso terapêutico , Coloides/uso terapêutico , Coloides/administração & dosagem , Soluções Isotônicas/uso terapêutico , Soluções Isotônicas/administração & dosagemRESUMO
Objective: To assess the efficacy of neoadjuvant treatment with PD-1 (programmed cell death protein 1) inhibitors combined with paclitaxel (albumin-conjugated) and cisplatin (TP regimen) for locally advanced hypopharyngeal squamous cell carcinoma and laryngeal organ function preservation. Methods: Data of 53 patients, including 51 males and 2 females, aged 38-70 years old, who were diagnosed with locally advanced hypopharyngeal squamous carcinoma confirmed by histology and enhanced CT at the Cancer Prevention and Control Center of Sun Yat-sen University during the initial treatment from January 1, 2019 to January 15, 2023, were retrospectively analyzed. All patients received neoadjuvant therapy with PD-1 inhibitors combined with albumin-bound paclitaxel (260 mg/m2) and cisplatin (60 mg/m2) for 3 to 4 cycles. The main outcome measures were larynx dysfunction-free survival (LDFS), overall survival (OS), and progression-free survival (PFS). Survival curves were plotted using the Kaplan-Meier method, and Cox multifactorial analysis was further performed if Cox univariate analysis was statistically significant. Results: The overall efficiency was 90.6% (48/53). The 1-year and 2-year LDFS rates were 83.8% (95%CI: 74.0% to 94.8%) and 50.3% (95%CI: 22.1% to 91.6%), the 1-year and 2-year OS rates were 95.2% (95%CI: 88.9% to 100.0%) and 58.2% (95%CI: 25.6% to 81.8%), and the 1-year and 2-year PFS rates were 83.9% (95%CI: 74.2% to 94.9%) and 53.5% (95%CI: 32.1% to 89.1%). Adverse events associated with the neoadjuvant therapy were mainly myelosuppression (45.3%), gastrointestinal reactions (37.7%) and hypothyroidism (20.8%). Conclusion: The neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma using PD-1 inhibitors combined with paclitaxel and cisplatin can provide with a higher survival rate with a improved laryngeal organ function preservation rate.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Neoplasias Hipofaríngeas , Terapia Neoadjuvante , Paclitaxel , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Cisplatino/uso terapêutico , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Adulto , Idoso , Neoplasias Hipofaríngeas/terapia , Neoplasias Hipofaríngeas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Albuminas/uso terapêutico , Albuminas/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidoresRESUMO
BACKGROUND: Long-term anti-angiogenesis leads to pruned vasculature, densely deposited extracellular matrix (ECM), and consequently reduced chemotherapy delivery in esophagogastric cancer (EGC). To address this issue, we evaluated the efficacy of adding a hyaluronidase or a NO-donor to the regimen of chemotherapy and anti-angiogenic drugs. METHODS: A patient-derived EGC xenograft model was developed. Grafted mice were randomly assigned to four experimental groups and one control group. The experimental groups received DC101, a murine angiogenesis inhibitor, and nab-paclitaxel (NPTX), with the addition of hyaluronidase (PEGPH20), or NO-donor (nitroglycerine, NTG), or their combination, respectively. We compared tumor growth during 17 days of treatment. We performed immunohistochemistry for ECM components hyaluronan (HA) and collagen, CD31 for endothelial cells, and γH2AX for DNA damage. The positively stained areas were quantified, and vessel diameters were measured using QuPath software. RESULTS: Prolonged DC101 treatment induced deposition of HA (p<0.01) and collagen (p<0.01). HA was effectively degraded by PEGPH20 (p<0.001), but not by NTG as expected. Both PEGPH20 (p<0.05) and NTG (p<0.01) dilated vessels collapsed in response to long-term DC101 treatment. However, only PEGPH20 (rather than NTG) was found to significantly inhibit tumor growth (p<0.05) in combination with NPTX and DC101. CONCLUSIONS: These findings suggest that the mechanical barrier of HA is the major reason responsible for the resistance developed during prolonged anti-angiogenesis in EGC. Incorporating PEGPH20 into the existing treatment regimen is promising to improve outcomes for patients with EGC.
Assuntos
Albuminas , Inibidores da Angiogênese , Neoplasias Esofágicas , Hialuronoglucosaminidase , Neovascularização Patológica , Paclitaxel , Neoplasias Gástricas , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Paclitaxel/farmacologia , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Hialuronoglucosaminidase/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Humanos , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Albuminas/farmacologia , Albuminas/administração & dosagem , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Camundongos , Ácido Hialurônico/farmacologia , Camundongos Nus , Feminino , Angiogênese , Anticorpos MonoclonaisRESUMO
BACKGROUND: Biliary tract cancers (BTCs) are a heterogeneous group of tumors with high malignancy, poor prognosis, and limited treatment options. AIM: To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs. METHODS: This open-label, non-randomized, double-center, phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University. Eligible patients were administered nab-paclitaxel (150 mg/m2, day 1) and capecitabine (2000 mg/m2, twice daily, days 1-7) in 14-day cycles until experiencing intolerable toxicity or disease progression. The primary outcome was the objective response rate (ORR). The secondary outcomes included the disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and safety. RESULTS: A total of 44 patients successfully completed the trial, with a median age of 64.00 years (interquartile range, 35.00-76.00), and 26 (59.09%) were females. Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage. Among the remaining 43 patients undergoing at least one imaging assessment, the ORR was 23.26% [95% confidence interval (CI): 11.80%-38.60%], and the DCR was 69.77% (95%CI: 53.90%-82.80%). The median OS was 14.1 months (95%CI: 8.3-19.9), and the median PFS was 4.4 months (95%CI: 2.5-6.3). A total of 41 patients (93.18%) experienced at least one adverse event (AE), with 10 patients (22.73%) encountering grade ≥ 3 AEs, and the most frequent AEs of any grade were alopecia (79.50%), leukopenia (54.55%), neutropenia (52.27%), and liver dysfunction (40.91%), and no treatment-related deaths were documented. CONCLUSION: Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.
Assuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar , Capecitabina , Paclitaxel , Intervalo Livre de Progressão , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Capecitabina/uso terapêutico , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Albuminas/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Resultado do TratamentoRESUMO
Nanoparticle-based systems are extensively investigated for drug delivery. Among others, with superior biocompatibility and enhanced targeting capacity, albumin appears to be a promising carrier for drug delivery. Albumin nanoparticles are highly favored in many disease therapies, as they have the proper chemical groups for modification, cell-binding sites for cell adhesion, and affinity to protein drugs for nanocomplex generation. Herein, this review summarizes the recent fabrication techniques, modification strategies, and application of albumin nanoparticles. We first discuss various albumin nanoparticle fabrication methods, from both pros and cons. Then, we provide a comprehensive introduction to the modification section, including organic albumin nanoparticles, metal albumin nanoparticles, inorganic albumin nanoparticles, and albumin nanoparticle-based hybrids. We finally bring further perspectives on albumin nanoparticles used for various critical diseases.
Albumin appears to be a promising carrier for drug delivery with superior biocompatibility and enhanced targeting capacity. This review focuses on the importance of albumin nanoparticles in drug delivery and concludes the recent fabrication techniques to prepare albumin nanoparticles, the modification strategies to require functional albumin nanoparticles, and critical applications of albumin nanoparticles in various diseases. The aim of this review is to help readers understand the significant potential of albumin nanoparticles in drug delivery.
Assuntos
Albuminas , Nanopartículas , Humanos , Albuminas/química , Albuminas/administração & dosagem , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Fármacos por Nanopartículas/químicaRESUMO
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
PURPOSE: After cardiac surgery, fluid bolus therapy (FBT) with 20% human albumin may facilitate less fluid and vasopressor administration than FBT with crystalloids. We aimed to determine whether, after cardiac surgery, FBT with 20% albumin reduces the duration of vasopressor therapy compared with crystalloid FBT. METHODS: We conducted a multicentre, parallel-group, open-label, randomised clinical trial in six intensive care units (ICUs) involving cardiac surgery patients deemed to require FBT. We randomised 240 patients to receive up to 400 mL of 20% albumin/day as FBT, followed by 4% albumin for any subsequent FBT on that day, or to crystalloid FBT for at least the first 1000 mL, with use of crystalloid or 4% albumin FBT thereafter. The primary outcome was the cumulative duration of vasopressor therapy. Secondary outcomes included fluid balance. RESULTS: Of 480 randomised patients, 466 provided consent and contributed to the primary outcome (mean age 65 years; median EuroSCORE II 1.4). The cumulative median duration of vasopressor therapy was 7 (interquartile range [IQR] 0-19.6) hours with 20% albumin and 10.8 (IQR 0-22.8) hours with crystalloids (difference - 3.8 h, 95% confidence interval [CI] - 8 to 0.4; P = 0.08). Day one fluid balance was less with 20% albumin FBT (mean difference - 701 mL, 95% CI - 872 to - 530). CONCLUSIONS: In patients after cardiac surgery, when compared to a crystalloid-based FBT, 20% albumin FBT was associated with a reduced positive fluid balance but did not significantly reduce the duration of vasopressor therapy.
Assuntos
Albuminas , Procedimentos Cirúrgicos Cardíacos , Soluções Cristaloides , Hidratação , Vasoconstritores , Humanos , Hidratação/métodos , Hidratação/normas , Hidratação/estatística & dados numéricos , Feminino , Masculino , Procedimentos Cirúrgicos Cardíacos/métodos , Idoso , Pessoa de Meia-Idade , Vasoconstritores/administração & dosagem , Vasoconstritores/uso terapêutico , Soluções Cristaloides/administração & dosagem , Soluções Cristaloides/uso terapêutico , Albuminas/administração & dosagem , Albuminas/uso terapêutico , Unidades de Terapia Intensiva/estatística & dados numéricos , Soluções Isotônicas/administração & dosagem , Soluções Isotônicas/uso terapêuticoRESUMO
OBJECTIVE: To investigate the clinical efficacy and adverse reactions of gemcitabine/nab-paclitaxel (AG regimen) combined with anlotinib and PD-1 inhibitors as a first-line treatment for advanced pancreatic cancer (PC). METHODS: Data of 52 patients with advanced PC who were treated in the Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) between August 2019 and March 2023 were retrospectively analyzed. According to the treatment regimen, patients were divided into two groups, including 27 patients in the chemotherapy group (AG regimen) and 25 patients in the combined treatment group (AG regimen combined with anlotinib and PD-1 inhibitors). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse reactions were compared between the two groups. The survival curves of the two groups were drawn using the Kaplan-Meier method, and the differences in PFS and OS between the two groups were compared by the log-rank test. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors influencing prognosis. RESULTS: The median OS and PFS in the combined treatment group were significantly longer than those in the chemotherapy group (OS, 12.8 vs. 7.9 months, P = 0.005; PFS, 5.6 vs. 4.4 months, P = 0.003). There was no significant difference in ORR between the two groups (32.0 % vs. 25.9 %, P = 0.629), and DCR in the combined treatment group was significantly better than that in the chemotherapy group (84.0 % vs. 59.3 %, P = 0.049). Grade 1-2 adverse reactions were predominant in both groups, and no adverse reaction-related deaths occurred. CONCLUSION: Compared with chemotherapy alone, AG regimen combined with anlotinib and PD-1 inhibitors exhibited to have a higher efficacy for the first-line treatment of advanced PC, and the adverse reactions were also controllable.
Assuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Gencitabina , Indóis , Paclitaxel , Neoplasias Pancreáticas , Quinolinas , Humanos , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Feminino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Idoso , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Albuminas/uso terapêutico , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Estudos Retrospectivos , Indóis/uso terapêutico , Indóis/administração & dosagem , Indóis/efeitos adversos , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Adulto , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do TratamentoRESUMO
Optimal fluid management during major surgery is of considerable concern to anesthesiologists. Although crystalloids are the first choice for fluid management, the administration of large volumes of crystalloids is associated with poor postoperative outcomes. Albumin can be used for fluid management and may protect renal function. However, data regarding the effects of albumin administration on kidney function are conflicting. As such, the present study aimed to investigate the effect of albumin administration on renal function in patients undergoing major surgery and compare its effects with those of crystalloid fluid. The Embase, Medline, Web of Science, Cochrane Library, and KoreaMed databases were searched for relevant studies. The primary endpoint of the meta-analysis was the incidence of postoperative kidney injury, including acute kidney injury and renal replacement therapy. Twelve studies comprising 2311 patients were included; the primary endpoint was analyzed in four studies comprising 1749 patients. Perioperative albumin levels in patients undergoing major surgery did not significantly influence kidney dysfunction (p = 0.98). Postoperative fluid balance was less positive in patients who underwent major surgery and received albumin than in those who received crystalloids. Owing to the limitations of this meta-analysis, it remains unclear whether albumin administration during major surgery is better than crystalloid fluid for improving postoperative renal function.
Assuntos
Complicações Pós-Operatórias , Humanos , Complicações Pós-Operatórias/etiologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Hidratação/métodos , Soluções Cristaloides/administração & dosagem , Albuminas/administração & dosagem , Período Pós-Operatório , Albumina Sérica Humana/administração & dosagemRESUMO
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
BACKGROUND: The multi-centre two-stage SCALOP-2 trial (ISRCTN50083238) assessed whether dose escalation of consolidative chemoradiotherapy (CRT) or concurrent sensitization using the protease inhibitor nelfinavir improve outcomes in locally advanced pancreatic cancer (LAPC) following four cycles of gemcitabine/nab-paclitaxel. METHODS: In stage 1, the maximum tolerated dose (MTD) of nelfinavir concurrent with standard-dose CRT (50.4 Gy in 28 fractions) was identified from a cohort of 27 patients. In stage 2, 159 patients were enrolled in an open-label randomized controlled comparison of standard versus high dose (60 Gy in 30 fractions) CRT, with or without nelfinavir at MTD. Primary outcomes following dose escalation and nelfinavir use were respectively overall survival (OS) and progression free survival (PFS). Secondary endpoints included health-related quality of life (HRQoL). RESULTS: High dose CRT did not improve OS (16.9 (60 % confidence interval, CI 16.2-17.7) vs. 15.6 (60 %CI 14.3-18.2) months; adjusted hazard ratio, HR 1.13 (60 %CI 0.91-1.40; p = 0.68)). Similarly, median PFS was not improved by nelfinavir (10.0 (60 %CI 9.9-10.2) vs. 11.1 (60 %CI 10.3-12.8) months; adjusted HR 1.71 (60 %CI 1.38-2.12; p = 0.98)). Local progression at 12 months was numerically lower with high-dose CRT than with standard dose CRT (n = 11/46 (23.9 %) vs. n = 15/45 (33.3 %)). Neither nelfinavir nor radiotherapy dose escalation impacted on treatment compliance or grade 3/4 adverse event rate. There were no sustained differences in HRQoL scores between treatment groups over 28 weeks post-treatment. CONCLUSIONS: Dose-escalated CRT may improve local tumour control and is well tolerated when used as consolidative treatment in LAPC but does not impact OS. Nelfinavir use does not improve PFS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Nelfinavir , Neoplasias Pancreáticas , Humanos , Nelfinavir/uso terapêutico , Nelfinavir/administração & dosagem , Nelfinavir/efeitos adversos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Dose Máxima Tolerável , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Gencitabina , Idoso de 80 Anos ou mais , Qualidade de Vida , Albuminas/administração & dosagem , Albuminas/uso terapêutico , Albuminas/efeitos adversos , Intervalo Livre de Progressão , Inibidores de Proteases/efeitos adversos , Inibidores de Proteases/uso terapêutico , Inibidores de Proteases/administração & dosagemRESUMO
A woman in her 40s underwent evaluation for abdominal pain, jaundice and acholic stools and was diagnosed with metastatic pancreatic head adenocarcinoma. She was enrolled in a clinical trial investigating the benefits of ibrutinib with nab-paclitaxel and gemcitabine, and subsequently received modified FOLFIRINOX. Over the course of 6 years on chemotherapy, she experienced complete regression of the pancreatic and liver lesions, as well as normalisation of her tumour markers. She has been off chemotherapy for 6 months with no evidence of disease and normal tumour markers. Despite advances in chemotherapy and surgical options, metastatic pancreatic adenocarcinoma continues to carry a grim prognosis. This case report demonstrates a rare case of a long-term survivor of unresectable metastatic pancreatic adenocarcinoma treated with chemotherapy alone.
Assuntos
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Leucovorina , Oxaliplatina , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Leucovorina/uso terapêutico , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Gencitabina , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Fluoruracila/uso terapêutico , Irinotecano/uso terapêutico , Adulto , Albuminas/uso terapêutico , Albuminas/administração & dosagem , Pessoa de Meia-Idade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/tratamento farmacológico , Resultado do TratamentoRESUMO
Cancer metastasis and recurrence are obstacles to successful treatment of aggressive cancer. To address this challenge, chemotherapy is indispensable as an essential part of comprehensive cancer treatment, particularly for subsequent therapy after surgical resection. However, small-molecule drugs for chemotherapy always cause inadequate efficacy and severe side effects against cancer metastasis and recurrence caused by lymph node metastases. Here, we developed doxorubicin-carried albumin nanocages (Dox-AlbCages) with appropriate particle sizes and pH/enzyme-responsive drug release for tumor and lymph node dual-targeted therapy by exploiting the inborn transport properties of serum albumin. Inspired by the protein-templated biomineralization and remote loading of doxorubicin into liposomes, we demonstrated the controlled synthesis of Dox-AlbCages via the aggregation or crystallization of doxorubicin and ammonium sulfate within albumin nanocages using a biomineralization strategy. Dox-AlbCages allowed efficient encapsulation of Dox in the core protected by the albumin corona shell, exhibiting favorable properties for enhanced tumor and lymph node accumulation and preferable cellular uptake for tumor-specific chemotherapy. Intriguingly, Dox-AlbCages effectively inhibited tumor growth and metastasis in orthotopic 4T1 breast tumors and prevented postsurgical tumor recurrence and lung metastasis. At the same time, Dox-AlbCages had fewer side effects than free Dox. This nanoplatform provides a facile strategy for designing tumor- and lymph node-targeted nanomedicines for suppressing cancer metastasis and recurrence.
Assuntos
Antibióticos Antineoplásicos , Doxorrubicina , Metástase Linfática , Camundongos Endogâmicos BALB C , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Animais , Feminino , Linhagem Celular Tumoral , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/uso terapêutico , Liberação Controlada de Fármacos , Nanopartículas/administração & dosagem , Nanopartículas/química , Humanos , Camundongos , Linfonodos/patologia , Linfonodos/efeitos dos fármacos , Linfonodos/metabolismo , Sistemas de Liberação de Medicamentos , Albuminas/administração & dosagem , Albuminas/química , Portadores de Fármacos/químicaRESUMO
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
INTRODUCTION: The prognosis of patients with advanced biliary tract cancer (BTC) is still poor, and new strategies improving patients' outcome are needed. In our trial we investigated safety and activity of nab-paclitaxel in combination with gemcitabine and oxaliplatin as first-line systemic treatment for patients with advanced BTC. METHODS: In this investigator-initiated, multicenter, dose-escalation, single-arm phase I/II trial, patients were accrued into cohorts of 3 patients and dose escalation was performed following the standard 3 + 3 rule. Primary endpoint was the proportion of patients free from progression at 6 months. Secondary endpoints included safety and tolerability of the combination; progression-free survival (PFS); overall survival (OS); objective response rate (ORR); duration of response. RESULTS: Between July 2017 and December 2020, 67 patients were treated. Among the 10 patients in the phase I, no dose-limiting toxicity was observed, and dose level 2 was defined as recommended phase II dose for the phase II part. At data cutoff, the 6-month PFS rate was 49.1 % (95 % CI 40.8-57.5 %) with 28 patients out of 57 free from progression or death at 6 months. Median PFS was 6.3 months (95 % CI 3.6-10.1) and median OS was 12.4 months (95 % CI 8-23). ORR was 20.89 %. Most common grade 3 and grade 1-2 drug-related adverse events were neutropenia and peripheral neuropathy, respectively. CONCLUSION: Triple chemotherapy demonstrated a favorable safety profile. However, the study did not meet its primary endpoint. Future studies will clarify the benefit of chemotherapy combinations in different settings. This trial is registered with ClinicalTrials.gov, NCT03943043.
Assuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar , Desoxicitidina , Gencitabina , Oxaliplatina , Paclitaxel , Humanos , Masculino , Feminino , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/mortalidade , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Albuminas/uso terapêutico , Adulto , Idoso de 80 Anos ou maisRESUMO
INTRODUCTION: Patients with pancreatic ductal adenocarcinoma (PDAC) remain a poor prognosis despite the development of chemotherapy. Although programmed cell death 1 (PD-1) blockade has shown great efficacy in various solid tumours, its application in treating PDAC is limited. Recent studies have indicated that chemotherapy or stereotactic body radiotherapy (SBRT) may improve the antitumour effect of PD-1 blockade in patients with PDAC. The objective of this study is to evaluate the efficacy and safety of combined therapy comprising PD-1 blockade, gemcitabine plus nab-paclitaxel chemotherapy and SBRT for patients with metastatic PDAC. METHODS AND ANALYSIS: This is a multicentre, single-arm, prospective phase II clinical trial. Forty-three patients diagnosed with metastatic PDAC will be enrolled. The eligible patients will be intravenously administered 1000 mg/m2 gemcitabine and 125 mg/m2 nab-paclitaxel on days 1 and 8 of the 21-day cycle. Serplulimab (200 mg) will be administered intravenously on day 1 of the 21-day cycle. Furthermore, during the second cycle, the patients will undergo SBRT with doses of 33 Gy in five fractions for primary lesions or doses of 24 Gy in three fractions for metastases. The primary endpoint is the 6-month progression-free survival (PFS) rate. The secondary endpoints overall survival, PFS, overall response rate, disease control rate, time to progression, duration of response, duration of disease control and safety. Moreover, this trial seeks to investigate biomarkers such as circulating tumour DNA and circulating hybrid cells in patients diagnosed with metastatic PDAC. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University. The study results will be presented at international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300073237.
Assuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Gencitabina , Paclitaxel , Neoplasias Pancreáticas , Radiocirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Albuminas/uso terapêutico , Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patologia , China , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Estudos Multicêntricos como Assunto , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Intervalo Livre de Progressão , Estudos Prospectivos , Radiocirurgia/métodosRESUMO
BACKGROUND: Lung cancer is associated with a high mortality rate worldwide. Non-small-cell lung cancer (NSCLC) is a major subtype of lung cancer. Carboplatin (CBDCA) plus nab-paclitaxel (PTX) has become a standard treatment for advanced unresectable NSCLC. However, treatment with nab-PTX has not been established as a standard therapy for resectable locally advanced (LA)-NSCLC. METHODS: We conducted a comprehensive study involving consecutive patients with locally advanced NSCLC who underwent induction therapy including nab-PTX followed by surgical resection. Fifteen patients with locally advanced NSCLC underwent induction therapy including nab-PTX followed by surgical resection. Concurrent chemoradiotherapy (CRT) consisted of weekly administration of nab-PTX (50 mg/m2) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and thoracic radiotherapy (50 Gy/25 fractions). RESULTS: The clinical stages were as follows: IIB (n =1), IIIA (n =12), and IIIC (n =2). Downstaging was observed in 73% (11/15) of patients on comparison with the clinical stage before concurrent CRT. Adverse drug reactions were observed in seven patients. Complete resection was performed in all patients. The re-evaluated pathological stage after pretreatment was diagnosed as stage 0 in three patients, stage IA1 in six, stage IA2 in one, and stage IIIA in five. The pathological effects of previous therapy were as follows: Ef3 (n =3), Ef2 (n =9), and Ef1a (n =3). CONCLUSION: The therapeutic effect of induction therapy including nab-PTX was promising. Induction CRT, including nab-PTX, followed by resection, may be a viable alternative treatment option for locally advanced NSCLC.
Assuntos
Albuminas , Carcinoma Pulmonar de Células não Pequenas , Quimioterapia de Indução , Neoplasias Pulmonares , Paclitaxel , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Feminino , Albuminas/uso terapêutico , Albuminas/administração & dosagem , Pessoa de Meia-Idade , Idoso , Quimioterapia de Indução/métodos , Estadiamento de Neoplasias , Pneumonectomia/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Ovarian cancer has the highest mortality among gynecologic cancers, primarily because it typically is diagnosed at a late stage and because of the development of chemoresistance in recurrent disease. Improving outcomes in women with platinum-resistant ovarian cancer is a substantial unmet need. Activation of the glucocorticoid receptor (GR) by cortisol has been shown to suppress the apoptotic pathways used by cytotoxic agents, limiting their efficacy. Selective GR modulation may be able to counteract cortisol's antiapoptotic effects, enhancing chemotherapy's efficacy. A previous phase 2 study has shown that adding intermittently dosed relacorilant, a selective GR modulator, to nab-paclitaxel improved outcomes, including progression-free survival (PFS) and overall survival (OS), with minimal added toxicity, in women with recurrent platinum-resistant ovarian cancer. The ROSELLA study aims to confirm and expand on these findings in a larger population. METHODS: ROSELLA is a phase 3, randomized, 2-arm, open-label, global multicenter study in women with recurrent, platinum-resistant, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Eligible participants have received 1 to 3 lines of prior systemic anticancer therapy, including ≥1 prior line of platinum therapy and prior treatment with bevacizumab, with documented progressive disease or intolerance to the most recent therapy. There is no biomarker-based requirement for participant selection. Participants are randomized 1:1 to receive intermittently dosed relacorilant in combination with nab-paclitaxel or nab-paclitaxel monotherapy. The study's primary efficacy endpoint is PFS as assessed by blinded independent central review. Secondary efficacy endpoints include OS, investigator-assessed PFS, objective response rate, best overall response, duration of response, clinical benefit rate at 24 weeks, and cancer antigen 125 response. The study is also evaluating safety and patient-reported outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05257408; European Union Drug Regulating Authorities Clinical Trials Database Identifier: 2022-000662-18.