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1.
Medicine (Baltimore) ; 99(43): e22814, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120804

RESUMO

RATIONALE: Although the cancer incidence continues to rise, cancer mortality has declined over the past decade, in large part due to more efficacious chemotherapeutic regimens thus, the ability to use first-line chemotherapeutic agents in the treatment of patients with cancer is crucial. Antineoplastic agents can potentially cause toxic and/or hypersensitivity reactions, that can have serious consequences. Anaphylaxis is a big pitfall in oncological patients; the most important aspect in diagnosing anaphylaxis is to precisely identify the offending agent to prevent future events. Paclitaxel (Taxol) is widely used as antitumor medication in the ovarian, breast, non-small-cell lung, and other cancers. Paclitaxel hypersensitivity reactions are frequently described in the literature, but fatalities are rarely reported. Due to the low solubility of paclitaxel, the compound requires dissolution in Cremophor EL, a derivative of castor oil. PATIENT CONCERNS: A 79-year-old man was affected by high-grade non-papillary urothelial carcinoma and underwent a radical cystectomy and prostatectomy with locoregional lymphadenectomy. DIAGNOSIS: Eight months later, relapse was detected, and penis amputation and left nephrostomy were performed. Multiple metastases to lymph nodes were detected. INTERVENTIONS: Palliative chemotherapy was started with Paclitaxel (110 mg) infused at a rate of 50 mL/h. Despite premedication with cetirizine dihydrochloride, dexamethasone, ondansetron, ranitidine, 20 min after Paclitaxel infusion starts, the patient developed general distress, followed by cardiac arrest. OUTCOMES: The mechanism of fatal paclitaxel-associated hypersensitivity reaction is uncertain and its solvent vehicle Cremophor EL may be involved. Several mechanisms have been postulated: an IgE-mediated mast cell degranulation induced by paclitaxel or Cremophor EL, a non-IgE-mediated idiosyncratic mast cell degranulation by paclitaxel or by Cremophor EL, and complement activation. Severe hypersensitivity reactions with fatal outcome are considered rare. LESSONS: The unpredictability and often dramatic reactions of Taxol cause substantial anxiety for doctors and caretakers. They also represent a significant logistic and financial burden on hospitals. Despite premedication, skin testing, and desensitization protocols administration of taxane-based, chemotherapy cannot be considered safe and severe to fatal hypersensitivity reactions cannot be prevented.


Assuntos
Hipersensibilidade a Drogas/etiologia , Glicerol/análogos & derivados , Paclitaxel/efeitos adversos , Neoplasias Urológicas/tratamento farmacológico , Idoso , Hipersensibilidade a Drogas/fisiopatologia , Glicerol/efeitos adversos , Glicerol/uso terapêutico , Humanos , Masculino , Mastócitos/metabolismo , Paclitaxel/uso terapêutico , Triptases/sangue , Neoplasias Urológicas/cirurgia
2.
Medicine (Baltimore) ; 99(39): e22250, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991420

RESUMO

It is unclear whether the use of antibiotics is related to the efficacy of gemcitabine plus nab-paclitaxel (GnP). Therefore, we investigated the association between the use of antibiotics and efficacy of GnP.We conducted a retrospective single center study from January 2014 to December 2018 in Hokkaido University Hospital.Ninety-nine patients were eligible for the study. Thirty-seven used antibiotics (U) and 62 did not use antibiotics (NU) during GnP therapy. In the U group, 15 patients used ß-lactam antibiotics, 21 used new quinolones, and 1 used carbapenem. The median progression-free survival was 5.8 and 2.7 months (hazards ratio [HR] .602, 95% confidence interval [CI] .391-.928, P = .022) and the median overall survival was 11.0 and 8.4 months (HR .768, 95% CI .491-1.202, P = .248) in the U and not use antibiotics groups, respectively. Antibiotic use (HR .489, 95% CI .287-.832, P = .008) and locally advanced pancreatic cancer (HR 1.808, 95% CI 1.051-3.112, P = .032) were independent prognostic factors for progression-free survival.Antibiotic use was associated with a higher efficacy of GnP, and therefore, it may be employed as a novel treatment strategy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Albuminas/uso terapêutico , Antibacterianos/uso terapêutico , Desoxicitidina/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos , Protocolos de Quimioterapia Combinada Antineoplásica , Estudos de Casos e Controles , Quimioterapia Adjuvante/métodos , Desoxicitidina/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos
3.
Int J Nanomedicine ; 15: 6409-6420, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922008

RESUMO

Aim: Tumor cell-derived microparticles (MP) can function as a targeted delivery carrier for anti-tumor drugs. Here, we aimed to generate paclitaxel-loaded microparticles (MP-PTX) from HeLa cells and examined its therapeutic potential on human cervical carcinoma. Methods: MP-PTX was generated from HeLa cells by ultraviolet radiation and subsequent centrifugation. The particle size, drug loading rate, and stability of MP-PTX were examined in vitro. Flow cytometry and the MTT assay were performed to test the inhibitory effect of MP-PTX using different cell lines. Immunodeficient mice bearing HeLa cervical carcinoma were treated with 0.9% normal saline, MP, paclitaxel (PTX) (2.5 mg/kg), or MP-PTX (PTX content identical to PTX group) every day for 6 consecutive days. Tumor volume and animal survival were observed. Micro 18F-FDG PET/CT was performed to monitor the therapeutic efficacy. The proliferation activity of cells and microvessel density in tumor tissues were determined by immunohistochemical staining using Ki-67 and CD31, respectively. Results: Dynamic laser scattering measurements showed that the particle size of MP-PTX was 285.58 ± 2.95 nm and the polydispersity index was 0.104 ± 0.106. And the particle size of MP-PTX was not change at 4°C for at least one week. More than 1% of PTX in the medium could be successfully encapsulated into HeLa cell-derived MP. When compared with PTX, MP-PTX treatment significantly increased apoptosis of tumor cells and reduced their proliferation. In addition, MP-PTX showed lower toxicity to normal human umbilical vein endothelial cells (HUVEC) than PTX. In vivo studies further demonstrated that MP-PTX treatment significantly inhibited the growth of cervical carcinoma, prolonged the survival of tumor-bearing mice, and reduced the toxicity of PTX. Immunohistochemical staining revealed that MP-PTX treatment led to decreased Ki-67 positive tumor cells and decreased microvessel density in tumor tissues. Conclusion: Our results demonstrated that HeLa-derived MP-PTX significantly enhanced the anti-cancer effects of PTX with reduced toxicity, which may provide a novel strategy for the treatment of cervical carcinoma.


Assuntos
Micropartículas Derivadas de Células/metabolismo , Paclitaxel/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Micropartículas Derivadas de Células/efeitos dos fármacos , Portadores de Fármacos/química , Células Endoteliais/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Fisiológica/efeitos dos fármacos , Paclitaxel/farmacologia , Tamanho da Partícula
4.
Ann Surg ; 272(5): 779-785, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32833766

RESUMO

OBJECTIVE: This study compared the efficacy of PF-based and CROSS-based neoadjuvant chemoradiotherapy for ESCC. BACKGROUND: PF-based regimen has been a standard regimen for ESCC, but it has been replaced by the CROSS regimen in the past few years, despite no prospective head-to-head comparative study has been performed. METHODS: This is a single center retrospective study. Records of all ESCC patients who have received neoadjuvant PF with 40 Gy radiotherapy in 20 daily fractions (PFRT Group) or CROSS with 41.4 Gy radiotherapy in 23 daily fractions (CROSS Group) during the period 2002 to 2019 were retrieved. Propensity score matching (1:1) was performed to minimize baseline differences. The primary and secondary endpoints were overall survival and clinicopathological response. Subgroup analysis ("CROSS Eligibility") was performed based on tumor length, cT-stage, cM-stage, age, and performance status. RESULTS: One hundred (out of 109) patients (CROSS group) and propensity score matched 100 (out of 210) patients (PFRT group) were included. Esophagectomy rates in CROSS and PFRT group were 69% and 76%, respectively (P = 0.268). R0 resection rates were 85.5% and 81.6% (P = 0.525) and the pathological complete remission rates were 24.6% and 35.5% (P = 0.154). By intention-to-treat, the median survival was 16.7 and 32.7 months (P = 0.083). For "CROSS Eligible subgroup," the median survival of the CROSS and PFRT group was 21.6 versus 44.9 months (P = 0.093). CONCLUSIONS: There is no statistically difference in survival or clinicopathological outcome between both groups, but the trend favors PFRT. Prospective head-to-head comparison and novel strategies to improve the outcomes in resectable ESCC are warranted.


Assuntos
Quimiorradioterapia , Neoplasias Esofágicas/terapia , Esofagectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos
5.
Lancet Oncol ; 21(10): 1269-1282, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32861273

RESUMO

BACKGROUND: BRCA1 or BRCA2-mutated breast cancers are sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors and platinum agents owing to deficiency in homologous recombination repair of DNA damage. In this trial, we compared veliparib versus placebo in combination with carboplatin and paclitaxel, and continued as monotherapy if carboplatin and paclitaxel were discontinued before progression, in patients with HER2-negative advanced breast cancer and a germline BRCA1 or BRCA2 mutation. METHODS: BROCADE3 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 147 hospitals in 36 countries. Eligible patients (aged ≥18 years) had deleterious germline BRCA1 or BRCA2 mutation-associated, histologically or cytologically confirmed advanced HER2-negative breast cancer, an Eastern Cooperative Oncology Group performance status of 0-2, and had received up to two previous lines of chemotherapy for metastatic disease. Patients were randomly assigned (2:1) by interactive response technology by means of permuted blocks within strata (block size of 3 or 6) to carboplatin (area under the concentration curve 6 mg/mL per min intravenously) on day 1 and paclitaxel (80 mg/m2 intravenously) on days 1, 8, and 15 of 21-day cycles combined with either veliparib (120 mg orally twice daily, on days -2 to 5) or matching placebo. If patients discontinued carboplatin and paclitaxel before progression, they could continue veliparib or placebo at an intensified dose (300 mg twice daily continuously, escalating to 400 mg twice daily if tolerated) until disease progression. Patients in the control group could receive open-label veliparib monotherapy after disease progression. Randomisation was stratified by previous platinum use, history of CNS metastases, and oestrogen and progesterone receptor status. The primary endpoint was investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy analyses were done by intention to treat, which included all randomly assigned patients with a centrally confirmed BRCA mutation, and safety analyses included all patients who received at least one dose of velilparib or placebo. This study is ongoing and is registered with ClinicalTrials.gov, NCT02163694. FINDINGS: Between July 30, 2014, and Jan 17, 2018, 2202 patients were screened, of whom 513 eligible patients were enrolled and randomly assigned. In the intention-to-treat population (n=509), 337 patients were assigned to receive veliparib plus carboplatin-paclitaxel (veliparib group) and 172 were assigned to receive placebo plus carboplatin-paclitaxel (control group). Median follow-up at data cutoff (April 5, 2019) was 35·7 months (IQR 24·9-43·6) in the veliparib group and 35·5 months (23·1-45·9) in the control group. Median progression-free survival was 14·5 months (95% CI 12·5-17·7) in the veliparib group versus 12·6 months (10·6-14·4) in the control group (hazard ratio 0·71 [95% CI 0·57-0·88], p=0·0016). The most common grade 3 or worse adverse events were neutropenia (272 [81%] of 336 patients in the veliparib group vs 143 [84%] of 171 patients in the control group), anaemia (142 [42%] vs 68 [40%]), and thrombocytopenia (134 [40%] vs 48 [28%]). Serious adverse events occurred in 115 (34%) patients in the veliparib group versus 49 (29%) patients in the control group. There were no study drug-related deaths. INTERPRETATION: The addition of veliparib to a highly active platinum doublet, with continuation as monotherapy if the doublet were discontinued, resulted in significant and durable improvement in progression-free survival in patients with germline BRCA mutation-associated advanced breast cancer. These data indicate the utility of combining platinum and PARP inhibitors in this patient population. FUNDING: AbbVie.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzimidazóis/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carboplatina/uso terapêutico , Paclitaxel/uso terapêutico , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Método Duplo-Cego , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Intervalo Livre de Progressão , Resultado do Tratamento
7.
Breast Cancer Res ; 22(1): 83, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758299

RESUMO

BACKGROUND: Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population. METHODS: EFFECT is an open-label, phase II trial wherein 160 women with advanced breast cancer aged ≥ 65 years were enrolled from 15 institutions within Italy. Patients were randomly assigned 1:1 to receive nab-paclitaxel 100 mg/m2 (arm A) or 125 mg/m2 (arm B) on days 1, 8, and 15 on a 28-day cycle, as first-line treatment for advanced disease. The primary endpoint was event-free survival (EFS), wherein an event was defined as disease progression (PD), functional decline (FD), or death. In each arm, the null hypothesis that the median EFS would be ≤ 7 months was tested against a one-sided alternative according to the Brookmeyer Crowley test. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 32.6 months, 140 events were observed in 158 evaluable patients. Median EFS was 8.2 months (90% CI, 5.9-8.9; p = 0.188) in arm A vs 8.3 months (90% CI, 6.2-9.7, p = 0.078) in arm B. Progression-free survival, overall survival, and response rates were similar in both groups. A higher percentage of dose reductions and discontinuations due to adverse events (AEs) was noted in arm B. The most frequently reported non-haematological AEs were fatigue (grade [G] 2-3 toxicity occurrence in arm A vs B, 43% and 51%, respectively) and peripheral neuropathy (G2-3 arm A vs B, 19% and 38%, respectively). CONCLUSION: Pre-specified outcomes were similar in both treatment arms. However, 100 mg/m2 was significantly better tolerated with fewer neurotoxicity-related events, representing a more feasible dose to be recommended for older patients with advanced disease. TRIAL REGISTRATION: EudraCT, 2012-002707-18 . Registered on June 4, 2012. NIH ClinicalTrials.gov, NCT02783222 . Retrospectively registered on May 26, 2016.


Assuntos
Albuminas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Albuminas/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/patologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Invasividade Neoplásica , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Prognóstico , Taxa de Sobrevida
8.
Medicine (Baltimore) ; 99(28): e21203, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664168

RESUMO

RATIONALE: Primary fallopian tube carcinoma (PFTC) is an extremely rare but invasive malignancy with a dismal prognosis. Very few data exist on the salvage treatment for patients with PFTC. Here we report a case showing an impressive response to immunotherapy combined with chemotherapy, which have never been reported before on patients with metastatic PFTC. PATIENT CONCERNS: A 42-year-old woman, who was diagnosed with PFTC in 2010, had been failed of multiple systemic therapies and antiangiogenic therapy because of the disease recurrence and progression. DIAGNOSIS: Metastatic primary fallopian tube carcinoma. INTERVENTIONS: The patient underwent surgery in May 2010 and had multi-line chemotherapies plus an anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody for about 9 years. Due to treatment failure the patient accepted the immunotherapy with the checkpoint inhibitor, pembrolizumab, combined with nab-paclitaxel from December 2018 to April 2019. OUTCOMES: The patient showed a complete response after 6 cycles treatment. Thus far, the patient is taking pembrolizumab as maintenance and remains in good health. LESSONS: Pembrolizumab combined with chemotherapy for treatment of PFTC may provide a positive antitumor effect in multiple metastatic lesions, but more clinical evidence is needed to confirm the efficacy and safety.


Assuntos
Albuminas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Feminino , Humanos
9.
Anticancer Res ; 40(7): 3995-4000, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620643

RESUMO

We present here the case of a 39-year-old man with metastatic pancreatic carcinoma receiving chemotherapy with the combination of gemcitabine and nab-paclitaxel as part of a clinical trial. Despite an impressive response to therapy, he ultimately developed profound anasarca, renal insufficiency, progressive cytopenias, and malignant hypertension 6 months into his treatment course. The diagnosis of gemcitabine-associated thrombotic microangiopathy (G-TMA) was made based on renal biopsy, and receipt of the anti-C5 monoclonal antibody eculizumab proved successful at reversing his deteriorating clinical course and improving his laboratory parameters. This case illustrates the importance of recognizing this rare but serious complication, and highlights one potential therapeutic option that can be used in the appropriate clinical context.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antimetabólitos Antineoplásicos/efeitos adversos , Inativadores do Complemento/uso terapêutico , Desoxicitidina/análogos & derivados , Microangiopatias Trombóticas/tratamento farmacológico , Adulto , Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/efeitos adversos , Evolução Fatal , Humanos , Masculino , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Microangiopatias Trombóticas/induzido quimicamente
10.
PLoS One ; 15(7): e0219632, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706829

RESUMO

INTRODUCTION: Surgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being first line treatment, temozolomide has only limited efficacy. METHODS: The development of injectable hydrogel-based carrier systems allows for the delivery of a wide range of chemotherapeutics that can achieve high local concentrations, thus potentially avoiding systemic side effects and wide-spread neurotoxicity. To test this modality in a realistic environment, we developed a diblock copolypeptide hydrogel (DCH) capable of carrying and releasing paclitaxel, a compound that we found to be highly potent against primary gliomasphere cells. RESULTS: The DCH produced minimal tissue reactivity and was well tolerated in the immune-competent mouse brain. Paclitaxel-loaded hydrogel induced less tissue damage, cellular inflammation and reactive astrocytes than cremaphor-taxol (typical taxol-carrier) or hydrogel alone. In a deep subcortical xenograft model of glioblastoma in immunodeficient mice, injection of paclitaxel-loaded hydrogel led to local tumor control and improved survival. However, the tumor cells were highly migratory and were able to eventually escape the area of treatment. CONCLUSIONS: These findings suggest this technology may be ultimately applicable to patients with deep-seated inoperable tumors, but as currently formulated, complete tumor eradication would be highly unlikely. Future studies should focus on targeting the migratory potential of surviving cells.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Glioblastoma/tratamento farmacológico , Hidrogéis/química , Paclitaxel/uso terapêutico , Peptídeos/química , Animais , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Sistema Nervoso Central/patologia , Portadores de Fármacos/química , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Paclitaxel/química , Taxa de Sobrevida , Temozolomida/química , Temozolomida/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Ann R Coll Surg Engl ; 102(8): 601-605, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32538115

RESUMO

INTRODUCTION: This study aimed to evaluate the safety and efficacy of paclitaxel-coated balloon compared with conventional plain balloon for the treatment of failing native dialysis access. MATERIALS AND METHODS: This prospective study included 60 patients presenting to the Kasr Alainy Hospitals and Aseer Central Hospital in the period from September 2015 to December 2017 with failing native vascular access. Dilatation with a plain balloon was done in 30 patients (group I) and with a paclitaxel-coated balloon in 30 patients (group II) with either stenosis or occlusion. The majority were outflow lesions, with 20 (66.7 %) patients in group I and 21 (70%) patients in group II. Mean balloon diameter was 7.1mm (± 1.5mm) compared with 6.5mm (± 1.2mm) and length 66mm (± 19.1mm) compared with 54.6mm (± 15.7mm), respectively. Safety endpoint was reported as 30 day's freedom from procedure-related major complications and mortality. Procedural technical success was defined as a residual diameter 30% or less for treated lesions. Target lesion primary patency, circuit primary patency and secondary patency were reported at 3, 6 and 12 months. RESULTS: There were no 30-day procedure-related major complications or mortality in either group. Procedural technical success of 100% was achieved in both groups. Target lesion primary patency, circuit primary patency and secondary patency in group II were better than in group I, especially at 12 months (90% vs 66.7%, 83.3% vs 60% and 96.7% vs 93.3%, respectively). There was a statistically significant difference in target lesion primary patency (p = 0.029) in patients who were treated with paclitaxel-coated balloon angioplasties. CONCLUSION: The paclitaxel-coated balloon proved to be safe and effective, and improved the patency of failing vascular access. Results are comparable with previous studies.


Assuntos
Angioplastia com Balão , Materiais Revestidos Biocompatíveis/uso terapêutico , Paclitaxel , Diálise Renal , Dispositivos de Acesso Vascular/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/instrumentação , Angioplastia com Balão/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Complicações Pós-Operatórias , Estudos Prospectivos , Diálise Renal/efeitos adversos , Diálise Renal/instrumentação , Diálise Renal/métodos , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/prevenção & controle
13.
Int J Nanomedicine ; 15: 3433-3445, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32523342

RESUMO

Background: Reconstituted lipoproteins (rLips) based on endogenous lipid nanostructures has been increasingly regarded as an excellent and promising antitumor drug delivery. However, some problems relating to the main component, apolipoprotein, for instance, rare source, unaffordable price, and low specificity of relevant receptor expression, become chief obstacles to its broad development and application. Purpose: The primary aim of this study is to develop biomimetic rLips by utilizing folic acid (FA)-modified bovine serum albumin (BSA) as a replacement for apolipoprotein and demonstrate its tumor targeting and antitumor efficacy. Methods: The amino groups of BSA were covalently conjugated with FA through the amide reaction. PTX-loaded nanostructured lipid carrier (termed as P-NLC) consisting of phospholipid, cholesteryl ester, triglyceride and cholesterol was prepared by the emulsification-evaporation method and utilized as the lipid core. FA-modified BSA (FA-BSA) was characterized for the protein substitute degree and attached with NLC by incubation-insert method to form the lipoprotein-mimic nanocomplex (termed as PFB-rLips). The morphology of nanoparticles was observed under transmission electron microscopy (TEM), and the particle size and zeta potential were determined using dynamic light scattering. In vitro release behavior of PTX from PFB-rLips was investigated with the dialysis method. Hemolysis tests were conducted to evaluate the biosecurity of PFB-rLips. Cell uptake and cytotoxicity assays were performed on human hepatocytes (LO2) and human hepatoma cells (HepG2). Tumor targeting was assessed using in vivo imaging system in H22 tumor-bearing mice model. Antitumor efficacy in vivo was investigated and compared between Taxol® (paclitaxel) formulation and PTX-incorporated nanoparticles in the same tumor model. Results: A fixed molar ratio 50:1 of FA to BSA was chosen as the optimal input ratio based on the balance between appropriate degree of protein substitution and amphiphilicity of FA-BSA. The morphology of FB-rLips exhibited as a homogeneous spherical structure featured by lipid cores surrounded with a cloudy protein shell observed under TEM. The particle size, zeta potential and encapsulation efficiency were 174.6±3.2 nm, -17.26±0.9 mV and 82.2±2.4%, respectively. In vitro release behavior of PTX from PFB-rLips was slow and sustained. The uptake of FB-rLips was much higher in HepG2 cells than in LO2 cells. Furthermore, the uptake of FB-rLips was significantly higher than that of rLips without FA involved (termed as B-rLips) and NLC in HepG2 cells. Hemolysis and cytotoxicity assays showed good biocompatibility of FB-rLips. The internalization mechanism of FB-rLips mainly depended on clathrin-mediated and caveolin-mediated endocytosis coupling with energy consumption, and FA receptors expressed on tumor cells played a critical role in cellular uptake process. CCK-8 studies demonstrated that PFB-rLips exhibited significantly better tumor killing ability than Taxol® (paclitaxel) formulation in vitro. Moreover, FB-rLips produced more excellent tumor-targeting properties than NLC through in vivo imaging assays. On the basis of this, PTX-loaded FB-rLips also performed more remarkable anticancer activity than other therapy groups in H22 tumor-bearing mice. Conclusion: FB-rLips would serve as a potential nanocarrier for improving tumor-targeting and therapeutic efficacy while reducing the side effects on normal tissues and organs.


Assuntos
Portadores de Fármacos/química , Ácido Fólico/uso terapêutico , Lipoproteínas/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Ácido Fólico/síntese química , Ácido Fólico/química , Hemólise/efeitos dos fármacos , Humanos , Camundongos , Nanopartículas/ultraestrutura , Neoplasias/patologia , Paclitaxel/química , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Tamanho da Partícula , Coelhos , Soroalbumina Bovina/química , Eletricidade Estática
14.
Int J Nanomedicine ; 15: 3319-3331, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32494132

RESUMO

Background: It is of great significance to develop intelligent co-delivery systems for cancer chemotherapy with improved therapeutic efficacy and few side-effects. Materials and Methods: Here, we reported a co-delivery system based on pH-sensitive polyprodrug micelles for simultaneous delivery of doxorubicin (DOX) and paclitaxel (PTX) as a combination chemotherapy with pH-triggered drug release profiles. The physicochemical properties, drug release profiles and mechanism, and cytotoxicity of PTX/DOX-PMs have been thoroughly investigated. Results and Discussion: The pH-sensitive polyprodrug was used as nanocarrier, and PTX was encapsulated into the micelles with high drug-loading content (25.6%). The critical micelle concentration (CMC) was about 3.16 mg/L, indicating the system could form the micelles at low concentration. The particle size of PTX/DOX-PMs was 110.5 nm, and increased to approximately 140 nm after incubation for 5 days which showed that the PTX/DOX-PMs had high serum stability. With decrease in pH value, the particle size first increased, and thenwas no longer detectable. Similar change trend was observed for CMC values. The zetapotential increased sharply with decrease in pH. These results demonstrated the pHsensitivity of PTX/DOX-PMs. In vitro drug release experiments and study on release mechanism showed that the drug release rate and accumulative release for PTX and DOX were dependent on the pH, showing the pH-triggered drug release profiles. Cytotoxicity assay displayed that the block copolymer showed negligible cytotoxicity, while the PTX/DOX-PMs possessed high cytotoxic effect against several tumor cell lines compared with free drugs and control. Conclusion: All the results demonstrated that the co-delivery system based on pH-sensitive polyprodrug could be a potent nanomedicine for combination cancer chemotherapy. In addition, construction based on polyprodrug and chemical drug could be a useful method to prepare multifunctional nanomedicine.


Assuntos
Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Micelas , Neoplasias/tratamento farmacológico , Paclitaxel/uso terapêutico , Pró-Fármacos/farmacologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Células NIH 3T3 , Neoplasias/patologia , Paclitaxel/farmacologia , Tamanho da Partícula , Polímeros/química , Eletricidade Estática
15.
Anticancer Res ; 40(6): 3129-3138, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487607

RESUMO

BACKGROUND/AIM: The combination of paclitaxel and carboplatin is the standard chemotherapy for ovarian cancer. Previous studies have implied that vitamin D (1,25-D3) may have growth inhibitory effects in ovarian cancer. This study aimed to investigate the effect of paclitaxel, carboplatin and 1,25-D3 on the growth of ovarian cancer cells in vitro, based on the hypothesis that 1,25-D3 might potentiate the effect of paclitaxel and/or carboplatin. MATERIALS AND METHODS: Three non-commercial ovarian carcinoma cell lines UT-OV-1(mucinous), UT-OV-3B (serous) and UT-OV-4 (endometrioid) were exposed to different concentrations of 1,25-D3, paclitaxel and carboplatin, respectively. The cell viability was measured using a Crystal violet assay kit. The cellular vitamin D receptor (VDR) mRNA levels were measured by qRT-PCR using the LightCycler equipment. RESULTS: The growth-inhibitory effect of the combination of paclitaxel and carboplatin was 56% in UT-OV-1, 33% in UT-OV-3B and 47% in UT-OV-4 cells. Single 1,25-D3 (10 µM) inhibited the growth of UT-OV-3B and UT-OV-4 by 23% and 28%, respectively, whereas no effect was seen in UT-OV-1 cells. These results are in line with the finding that the expression of VDR was high in UT-OV-3B and UT-OV-4, but very low in UT-OV-1. The combination of 1,25-D3, paclitaxel and carboplatin resulted in 61%, 46% and 58% growth reduction in UT-OV-1, UT-OV-3B and UT-OV-4 cells, respectively. The additive effect of 1,25-D3 was 21% in UT-OV-4, 20% in UT-OV-3B and 12% in UT-OV-1 cell line. CONCLUSION: The results imply that combining 1,25-D3 with paclitaxel and carboplatin may potentiate their growth inhibitory effect on ovarian cancer cells with high VDR expression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Técnicas In Vitro/métodos , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Receptores de Calcitriol/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carboplatina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia
16.
Medicine (Baltimore) ; 99(25): e20734, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569214

RESUMO

BACKGROUD: Paclitaxel (PTX) has become a widely used second-line therapy for advanced gastric cancer. There exists controversy whether targeted therapy combined with PTX can provide additional benefit over PTX alone. Therefore, a meta-analysis was carried out to evaluate the efficacy and safety of the two therapy regimes. METHODS: We searched systematically for studies from the databases of PubMed, Embase, Web of Science and the Cochrane Library published between January 2000 and August 2019. Only randomized controlled trials were eligible. Statistical analysis was performed by meta-analysis. The primary end points were progression-free survival and overall survival, objective response rate and adverse events were the secondary end points. RESULTS: A total of 4 randomized controlled trials with 1574 patients (PTX + targeted therapy, n = 786; PTX, n = 788) were included for the final analysis. As compared with PTX monotherapy, PTX + targeted therapy significantly improved progression-free survival (hazard ratio  = 0.88, 95% confidence interval [CI] 0.84-0.92, P < .001), overall survival (hazard ratio  = 0.90, 95% CI: 0.86-0.95, P < .001) and was associated with a better objective response rate (RR = 1.80; 95% CI: 1.45-2.24; P < .001). PTX+targeted therapy group significantly increased incidences of grade 3 to 5 neutropenia, fatigue and neuropathy (P < .05). No statistically significant differences were observed in the incidences of grade 3 to 5 anemia, decreased appetite, nausea, diarrhea and abdominal pain between the two treatments (P >.05). CONCLUSIONS: Second-line PTX+targeted therapy is a more effective treatment option with tolerable safety profile for advanced gastric cancer as a result of improved survival, though with additional toxicity.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Neoplasias Gástricas/patologia
17.
Expert Rev Med Devices ; 17(6): 533-539, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32525406

RESUMO

INTRODUCTION: The femoropopliteal (FP) segment is a common site of involvement in peripheral arterial disease (PAD) and endovascular therapy has been shown to be safe and effective in the treatment of FP disease. Self-expanding nitinol stents are now frequently used for the treatment of FP disease but in-stent restenosis (ISR) remains a major issue that can lead to recurrence of symptoms requiring repeated revascularizations. Compared to plain old balloon angioplasty (POBA), drug-coated balloons (DCBs) have shown promising results with reduction of ISR rates and target lesion revascularization (TLR). AREAS COVERED: The aim of this review is to describe the mechanisms and classification of ISR and to summarize the available data on outcomes of all DCBs, especially in the treatment of FP ISR. EXPERT OPINION: Currently available data supports the use of DCBs as a first-line therapy in patients with FP ISR, with lower rates of TLR and higher patency rates at 1-year follow-up, when compared to POBA. Further randomized studies are essential to evaluate longer term safety and efficacy of DCBs.


Assuntos
Angioplastia com Balão/efeitos adversos , Reestenose Coronária/tratamento farmacológico , Artéria Femoral/cirurgia , Paclitaxel/uso terapêutico , Artéria Poplítea/cirurgia , Stents/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Life Sci ; 256: 117943, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32531377

RESUMO

AIM: The aim of this study was to improve the therapeutic index of chemotherapeutic drugs on glioblastoma cells through an improved co-drug delivery system. MATERIALS AND METHODS: Methotrexate (MTX) and paclitaxel (PTX) were co-loaded into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) coated with polyvinyl alcohol (PVA) and Poloxamer188 (P188). KEY FINDINGS: The mean size of the NPs was about 212 nm, with a zeta potential of about -15.7 mV. Encapsulation efficiency (EE%) and drug loading (DL%) were determined to be 72% and 4% for MTX and 85% and 4.9% for PTX, respectively. The prepared NPs were characterized by differential thermal analysis (DTA) and thermogravimetric analysis (TGA). Moreover, an in vitro sustained release profile was observed for both drug loaded PLGA NPs. Glioblastoma cellular uptake of the NPs was confirmed by fluorescence microscopy and cell survival rate was investigated through the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method after 48 h of incubation showing IC50 values of 24.5 µg·mL-1 for PTX and 9.5 µg·mL-1 for MTX for the MTX/PTX co-loaded PLGA nanoparticles coated with PVA/P188 (Co-2 NPs). Apoptosis and necrosis were also studied via flow cytometry, the lactate dehydrogenase (LDH) assay and the amount of anti-apoptotic protein (Bcl-2) expression. Blood compatibility of the co-delivery of PTX and MTX loaded PLGA NPs was investigated using a hemolysis method as well. SIGNIFICANCE: The co-delivery of PTX and MTX loaded PLGA NPs is promising for the treatment of glioblastoma compared to their respective free drug formulations and, thus, should be further investigated.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Composição de Medicamentos , Glioblastoma/tratamento farmacológico , Metotrexato/uso terapêutico , Nanopartículas/química , Paclitaxel/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Antineoplásicos/farmacologia , Apolipoproteínas/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Glioblastoma/patologia , Hemólise/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , L-Lactato Desidrogenase/metabolismo , Metotrexato/farmacologia , Nanopartículas/ultraestrutura , Paclitaxel/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos
19.
Medicine (Baltimore) ; 99(24): e20558, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541479

RESUMO

BACKGROUND: Cervical cancer (CC) is a very common and malignant tumor in female population. Although a variety of single medications are reported to treat this condition, they all have limited efficacy. Previous studies have reported the combination of paclitaxel, carboplatin, and bevacizumab (PCB) can be used for the treatment of patients with CC effectively. However, no systematic review has explored its efficacy and safety. This study will address its efficacy and safety systematically and comprehensively. METHODS: The following electronic databases will be retrieved from their inceptions to the January 1, 2020 to identify all potential associated studies: MEDLINE, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Google scholar, and Chinese Biomedical Literature Database. We will include randomized controlled trials (RCTs) of adult women (≥18 years) with CC globally. Eligible interventions will target any forms of PCB. The study methodological quality of all included studies will be appraised using Cochrane risk of bias tool. Statistical analysis will be undertaken using RevMan 5.3 software. In addition, we will perform a narrative synthesis to describe quality and content of the evidence. RESULTS: This study will summarize recent evidence and provide quality evidence for the efficacy and safety of PCB on CC. CONCLUSION: The findings of this study will seek to identify the efficacy and safety of PCB and suggest future directions for research efforts targeting CC among this population. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040195.


Assuntos
Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Carboplatina/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Feminino , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
20.
PLoS One ; 15(5): e0232240, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379763

RESUMO

AIM: That clinical trial (RAINBOW) showed that a 7.4 months overall survival benefit with the combination therapy with ramucirumab (RAM) and paclitaxel (PAC) as second-line therapy for patients with recurrent or metastatic gastric or gastro-oesophageal junction adenocarcinoma, compared with placebo (PLA) plus paclitaxel. We performed an analysis to assess the cost-effectiveness of RAM from a Chinese perspective and recognized the range of drug costs. METHODS: By building a Markov model to estimate quality-adjusted life-years (QALYs), life-years (LYs) and lifetime costs. Transition probabilities, costs and utilities were estimated for the published literature, Chinese health care system and local price setting. We performed threshold analyses and probabilistic sensitivity analyses to evaluate the uncertainty of the model. RESULTS: Compared with PLA strategy, RAM strategy provided an incremental survival benefit of 1.22 LYs and 0.64 QALYs. The probabilistic sensitivity analysis showed that when RAM costs less than $151 or $753 per 4 weeks, the incremental cost-effectiveness ratio (ICER) approximated the willingness-to-pay threshold (WTP), suggesting that there was 50% likelihood that the ICER for RAM + PAC would be less than $44528.4 per QALY or $48121 per QALY, respectively. CONCLUSIONS: For patients with advanced gastric or gastro-oesophageal junction adenocarcinoma who fail first-line chemotherapy, our results are conducive to the multilateral drug price guidance negotiations of RAM in China.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Grupo com Ancestrais do Continente Asiático , China , Análise Custo-Benefício , Neoplasias Esofágicas/economia , Feminino , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Modelos Econômicos , Paclitaxel/economia , Paclitaxel/uso terapêutico , Intervalo Livre de Progressão , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Estômago/patologia , Neoplasias Gástricas/economia
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