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1.
Ann Palliat Med ; 11(7): 2382-2394, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35927773

RESUMO

BACKGROUND: Long-term benefit of nanoparticle-albumin-bound paclitaxel (Nab-P) over conventional taxanes in breast cancer patients is still controversial. We conducted a systematic review of studies to identify the optimal taxanes for selection in clinical practice. METHODS: We enrolled studies if they enrolled adults (age ≥18) with breast cancer, compared Nab-P (at any dose) to conventional paclitaxel or docetaxel, provided information on survival data, the response rate, or adverse events, were randomized controlled trials, case-control studies, or cohort studies, and were published in English (including those published online, ahead of the print publication). Cochrane Collaboration tool and Newcastle-Ottawa scale were used for bias-risk assessment. Grading of recommendations assessment, development, and evaluation approach were adopted for the quality of evidence evaluation. The outcomes included the overall response rate, pathological complete response rate, progression-free survival, overall survival, allergic reaction, leukopenia, neutropenia, and sensory neuropathy. RESULTS: A total of 20 eligible clinical studies comprising 11,046 patients were included in the analysis. No significant publication bias was observed based on a visual inspection of the funnel plots for progressionfree survival (PFS), and overall survival (OS). Compared to the conventional taxanes group (n=2,743), the Nab-P group (n=1,680) had a significantly higher ORR (RR =1.21, 95% CI: 1.07-1.37; P=0.003) and pCR (RR =1.33, 95% CI: 1.17-1.51; P<0.001). The Nab-P group also had a lower risk of disease progression and death than the conventional taxanes group (HR =0.89, P=0.269). Additionally, the Nab-P group had fewer treatment-related allergic reactions (RR =0.74, 95% CI: 0.59-0.93; P=0.009) and less grade ≥4 neutropenia (RR =0.39, 95% CI: 0.20-0.77; P=0.007) than the conventional taxanes group. The incidence of any-grade of neutropenia and sensory neuropathy were significantly higher in the Nab-P group than the conventional taxanes group (P=0.009 and P<0.001, respectively). DISCUSSION: The Nab-P in all stages of breast cancer patients had significantly better efficacy and tolerance than the conventional taxanes. Moreover, preventive strategies for reducing the incidence of Nab-P induced sensory neuropathy should be explored in future studies.


Assuntos
Neoplasias da Mama , Nanopartículas , Neutropenia , Adulto , Paclitaxel Ligado a Albumina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Nanopartículas/uso terapêutico , Neutropenia/induzido quimicamente , Paclitaxel/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxoides/efeitos adversos
2.
Cell Mol Biol (Noisy-le-grand) ; 67(5): 263-268, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35818244

RESUMO

This study aimed to evaluate the efficacy and safety of transarterial infusion of programmed cell death receptor-1 (PD-1) antibody therapy in advanced or metastatic acral and mucosal melanomas. Eleven patients with acral or mucosal melanoma were referred to the department of Internal Medicine-Oncology in Huazhong University of Science and Technology Union Shenzhen Hospital from January 2019 to August 2020. These patients received transarterial infusions of PD-1 antibody and intravenous infusions of albumin-bound paclitaxel. The median duration of follow-up was 8 months. The patients were treated with transarterial infusion of PD-1 antibody and intravenous infusion of albumin-bound paclitaxel. in study, We collected and recorded immunotherapy-related adverse events. The results showed that the response rate (RR) and the disease control rate (DCR) of the patients (seven with acral melanoma, four with mucosal melanoma) were 54.5 % and 90.9 %, respectively. No grade 3-4 adverse events or major complications were observed during the study. The median progression-free survival was 10 months. The transarterial infusion of PD-1 antibody has remission and control effects on acral and mucosal melanomas, which is important for the clinical care of these patients.


Assuntos
Melanoma , Neoplasias Cutâneas , Paclitaxel Ligado a Albumina/uso terapêutico , Humanos , Imunoterapia , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia
3.
BMC Womens Health ; 22(1): 224, 2022 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690772

RESUMO

OBJECTIVE: This study aimed to compare the efficacy of albumin-bound paclitaxel combined with carboplatin (Nab-TC) with that of traditional solvent-based paclitaxel combined with carboplatin (TC) as neoadjuvant chemotherapy (NAC) regimens for primary epithelial ovarian cancer. METHODS: Eighty patients with advanced primary epithelial ovarian cancer admitted for treatment at the Harbin Medical University Cancer Hospital from January 2015 to January 2020 were retrospectively selected. All patients underwent surgery after 1-4 courses of NAC with Nab-TC or TC regimen. Among the patients included for study, 40 patients in each group. RESULTS: The ORR in Nab-TC group was better compared to TC group (45% vs 40%), but the difference was not significant (P = 0.651). While the reduction rate of CA-125 value in the Nab-TC group was significantly better (P < 0.05). The postoperative complication rate such as postoperative blood transfusion (5% vs 35%) and postoperative infusion of human albumin (25% vs 55%) were significantly lower relative to the TC group. The median progression-free survival of the Nab-TC group was significantly longer relative to the TC group (20 months vs 13 months, P = 0.012), and the patient's quality of life was also better in the Nab-TC group (P < 0.05). Our study demonstrated that Nab-TC regimen and R0 represented the independent prognostic factors. CONCLUSION: The efficacy of the Nab-TC regimen as NAC for advanced primary epithelial ovarian cancer was non-inferior to that of the TC regimen along with a lower incidence of adverse reactions, a longer PFS and a higher quality of life, supporting its therapeutic value in the clinic.


Assuntos
Paclitaxel Ligado a Albumina , Neoplasias Ovarianas , Paclitaxel Ligado a Albumina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Terapia Neoadjuvante , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/etiologia , Paclitaxel/uso terapêutico , Qualidade de Vida , Estudos Retrospectivos
4.
J Cancer Res Ther ; 18(2): 482-487, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35645118

RESUMO

Aims: This study evaluates the safety and preliminary antitumor efficacy of camrelizumab with albumin-binding paclitaxel and cisplatin as first-line therapy for patients with recurrent or metastatic cervical carcinoma. Methods and Material: In this phase 2, open-label, prospective study, 35 patients with recurrent or metastatic cervical carcinoma with no previous systemic chemotherapy were included. The patients were treated with a maximum of six cycles of camrelizumab on day 1, albumin-binding paclitaxel, and carboplatin on day 2, every 3 weeks, followed by camrelizumab once every 3 weeks. The primary outcomes were objective response rate (ORR) and disease control rate (DCR). Secondary outcomes were duration of response (DoR) and safety. Furthermore, 27 patients were included in the per-protocol set for efficacy analysis, whereas for the safety analysis, all patients were included. Results: The median follow-up was 4.53 months, and the complete response, partial response, and stable disease were also achieved in 4 (14.81%), 6 (22.22%), and 13 (48.15%) patients. The ORR and DCR were 40.00% (95% confidence interval: 21.13-61.33%) and 92.00% (73.97-99.01%), respectively. The median DoR was 6.70 months. In addition, the most common adverse events (AEs) were reactive cutaneous capillary endothelial proliferation (RCCEP) (23, 65.71%), gastrointestinal reaction (8, 22.86%), and fever (8, 22.86%). Grade 3 AEs included 5 (14.29%) myelosuppression, and grade 4 AEs included 1 (2.86%) RCCEP and 1 (2.86%) bladder inflammation. Conclusions: Combination therapy of camrelizumab and albumin-bound paclitaxel and carboplatin shows promising efficacy and manageable toxicities in patients with recurrent or metastatic cervical cancer.


Assuntos
Paclitaxel Ligado a Albumina , Neoplasias do Colo do Útero , Albuminas , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina , Doença Crônica , Feminino , Humanos , Paclitaxel/uso terapêutico , Estudos Prospectivos , Neoplasias do Colo do Útero/patologia
5.
J Int Med Res ; 50(4): 3000605221094274, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35469479

RESUMO

There is heterogeneity in cancer patients' responses to immune checkpoint inhibitors (ICIs), including hyperprogression, which is very rapid tumor progression following immunotherapy, and pseudoprogression, which is an initial increase followed by a decrease in tumor burden or in the number of tumor lesions. This heterogeneity complicates clinical decisions because either premature withdrawal of the treatment or prolonged ineffective treatment harms patients. We presented two patients treated with ICIs with heterogeneous responses. One patient had Merkel cell carcinoma in the right thigh, and the other had nasopharyngeal squamous carcinoma. The first patient was treated with sintilimab and the second with sintilimab combined with abraxane. In the first patient, subcutaneous lesions grew substantially after the first cycle of treatment with sintilimab. In the second patient, subcutaneous lesions grew gradually after the second cycle of treatment with sintilimab combined with abraxane. In both cases, biopsy examination confirmed that newly emerged lesions were metastases of the primary tumor. These two cases remind clinicians that when subcutaneous nodules appear after treatment with ICIs, pathological biopsy is needed to determine the nature-pseudoprogression or rapid progression-of the disease course.


Assuntos
Paclitaxel Ligado a Albumina , Carcinoma , Progressão da Doença , Humanos , Inibidores de Checkpoint Imunológico , Fatores Imunológicos , Imunoterapia/efeitos adversos
6.
Nanomedicine (Lond) ; 17(10): 683-694, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35393861

RESUMO

Aim: The present study aimed to retrospectively compare the efficacy and safety between liposomal paclitaxel (Lps-P) and nanoparticle albumin-bound paclitaxel (Nab-P) in neoadjuvant systemic treatment (NST) of breast cancer. Materials & methods: Two hundred thirty-five patients who were diagnosed with invasive breast cancer and then received dose-dense NST with epirubicin and cyclophosphamide followed by paclitaxel were enrolled. Results: Nab-P has an advantage in improving the total and axillary-only pathologic complete response rate over Lps-P. Although Nab-P can cause a higher incidence and severity of peripheral sensory neuropathy (PSN), most symptoms are temporary and reversible. In the Lps-P group, the proportion of patients with residual irreversible PSN is larger. Conclusion: Nab-P might be superior to Lps-P in NST of breast cancer.


Neoadjuvant systemic treatment (NST) is recommended for many patients with breast cancer before they undergo surgery to remove the cancer. This study retrospectively compared the efficacy and safety of two potential NST drugs, liposomal paclitaxel (Lps-P) and nanoparticle albumin-bound paclitaxel (Nab-P). Two hundred thirty-five patients participated in the study. These patients had been diagnosed with invasive breast cancer and were recommended NST with paclitaxel before surgery. The results showed that more participants who received Nab-P had no signs of cancer in their tissue samples from their breasts and armpit lymph nodes than participants who received Lps-P. Although Nab-P can cause a higher incidence and severity of peripheral sensory neuropathy (PSN), most symptoms are temporary and reversible. In conclusion, Nab-P might be superior to Lps-P for NST.


Assuntos
Neoplasias da Mama , Nanopartículas , Paclitaxel Ligado a Albumina/uso terapêutico , Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Lipopolissacarídeos , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
7.
Drug Deliv ; 29(1): 728-742, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35244505

RESUMO

Albumin-bound paclitaxel (abPTX) has been widely used in cancer treatment. However, dose-related side effects, such as myelosuppression, restrict its clinical application. Cell-based targeting drug delivery is a promising way to mitigate systematic side-effects and improve antitumoral efficacy. In this study, we demonstrated that reassembled abPTX could be engulfed by neutrophils in vivo and delivered to tumor site, thus improving therapeutic efficacy and mitigating myelosuppression. First, in vitro analysis confirmed that reassembling of abPTX formed uniform and stable serum albumin nanoparticles (NP-abPTX) with size of 107.5 ± 2.29 nm and reserved the ability to kill tumor cells. Second, we found that NP-abPTX could be engulfed by activated neutrophil in vitro and in vivo but do not affect neutrophils' function, such as chemotaxis and activation. In a murine tumor model, we further proved that local radiotherapy (RT) induced inflammation activated peripheral neutrophils to capture venous infused NP-abPTX and carry them into tumor tissue. As compared to abPTX, infusion of NP-abPTX dramatically enhanced inhibition of tumor growth treated by local RT and mitigated hematotoxicity. Therefore, our study demonstrated a novel strategy to mitigate side-effects and to improve tumor killing efficacy of abPTX through neutrophil-mediated targeting drug delivery.


Assuntos
Paclitaxel Ligado a Albumina , Nanopartículas , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Camundongos , Neutrófilos , Paclitaxel
8.
Medicine (Baltimore) ; 101(6): e28863, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35147134

RESUMO

ABSTRACT: In addition to advanced non-small cell lung cancer, nanoparticle albumin-bound paclitaxel (nab-PTX) may also harbor potential benefit for patients with relapsed small cell lung cancer (SCLC), since weekly paclitaxel (PTX) shows modest activity for relapsed SCLC. We evaluated the efficacy and safety of both weekly nab-PTX and PTX for relapsed SCLC.We retrospectively reviewed 52 consecutive relapsed SCLC patients who were treated with weekly nab-PTX or PTX at our hospital.The response rate, median progression-free survival and overall survival with nab-PTX and PTX were 5.6 vs 8.8%, 3.2 vs 1.7 months, and 5.4 vs 4.5 months, respectively. No statistically significant differences were observed. There was no statistical difference between the 2 groups for ≥Grade 3 adverse events.Weekly nab-PTX and PTX showed similar activity for relapsed SCLC. The toxicity profile of nab-PTX was equally tolerable to that of PTX.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas , Carcinoma de Pequenas Células do Pulmão , Paclitaxel Ligado a Albumina/uso terapêutico , Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/efeitos adversos , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
9.
Int J Biol Sci ; 18(3): 911-922, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35173526

RESUMO

Pancreatic cancer is a dismal malignancy with poor prognosis. In spite of progress in surgical technology, chemotherapy is still the cornerstone in the multi-disciplinary treatment. Albumin-bound paclitaxel is a first-line treatment for PDAC patients. Yet the response rate of the drug is far from satisfying. SOX8 is a member of the sex determining region Y-boxes family, which is potentially related to the chemoresistance of tumor. Patient with high expression of SOX8 were insensitive to albumin-bound paclitaxel. SOX8 reduced apoptosis and G2/M cell cycle arrest caused by albumin-bound paclitaxel. SOX8 transcriptionally regulated EZH2, which reduced expression of SPARC by promoting the methylation of SPARC, thereby reducing the transport of albumin-bound paclitaxel in pancreatic cancer cells. EZH2 inhibitor, UNC1999, can reverse the effect of SOX8 on chemo-resistance of albumin-bound paclitaxel. Collectively, our data revealed SOX8/EZH2/SPARC signaling induced primary chemo-resistance of albumin-bound paclitaxel in pancreatic ductal adenocarcinoma.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Paclitaxel Ligado a Albumina/metabolismo , Paclitaxel Ligado a Albumina/farmacologia , Paclitaxel Ligado a Albumina/uso terapêutico , Apoptose/genética , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , Osteonectina/genética , Osteonectina/farmacologia , Osteonectina/uso terapêutico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/metabolismo , Fatores de Transcrição SOXE/metabolismo
10.
J Cell Mol Med ; 26(7): 1955-1968, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35174623

RESUMO

Nab-paclitaxel (Abraxane), which is a nanoparticle form of albumin-bound paclitaxel, is one of the standard chemotherapies for pancreatic ductal adenocarcinoma (PDAC). This study determined the effect of Abraxane in combination with a fusion protein, hIL15-ABD, on subcutaneous Panc02 and orthotopic KPC C57BL/6 murine PDAC models. Abraxane combined with hIL15-ABD best suppressed tumour growth and produced a 40%-60% reduction in the tumour size for Panc02 and KPC, compared to the vehicle group. In the combination group, the active form of interferon-γ (IFN-γ)-secreting CD8+ T cells and CD11b+ CD86+ M1 macrophages in tumour infiltrating lymphocytes (TILs) were increased. In the tumour drainage lymph nodes (TDLNs) of the combination group, there was a 18% reduction in CD8+ IFN-γ+ T cells and a 0.47% reduction in CD4+ CD25+ FOXP3+ regulatory T cells, as opposed to 5.0% and 5.1% reductions, respectively, for the control group. Superior suppression of CD11b+ GR-1+ myeloid-derived suppressor cells (MDSCs) and the induction of M1 macrophages in the spleen and bone marrow of mice were found in the combination group. Abraxane and hIL15-ABD effectively suppressed NF-κB-mediated immune suppressive markers, including indoleamine 2,3-dioxygenase (IDO), Foxp3 and VEGF. In conclusion, Abraxane combined with hIL15-ABD stimulates the anticancer activity of effector cells, inhibits immunosuppressive cells within the tumour microenvironment (TME) of PDAC, and produces a greater inhibitory effect than individual monotherapies.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Paclitaxel Ligado a Albumina/farmacologia , Paclitaxel Ligado a Albumina/uso terapêutico , Albuminas/uso terapêutico , Animais , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Ductal Pancreático/patologia , Modelos Animais de Doenças , Humanos , Interleucina-15 , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/patologia , Microambiente Tumoral
11.
Int J Clin Oncol ; 27(4): 684-694, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35089459

RESUMO

BACKGROUND: Paclitaxel plus ramucirumab (PTX + RAM) is the standard second-line chemotherapy for unresectable advanced or recurrent gastric cancer (AGC). Nanoparticle albumin-bound paclitaxel (nab-PTX) is an improved, more convenient form of PTX and is non-inferior to PTX. Although some retrospective and single-arm phase II studies regarding nab-PTX + RAM have been reported, comparative studies are lacking. Here, we compared the efficacy and toxicity of nab-PTX + RAM and PTX + RAM using propensity score matching. METHODS: Clinical data of 265 patients treated for AGC with nab-PTX + RAM or PTX + RAM were retrospectively collected. Nab-PTX was administered at dosages of 100 mg/m2, replacing PTX in the standard PTX + RAM regimen. Progression-free survival (PFS), overall survival (OS), and toxicity were compared using 1:1 propensity score matching. RESULTS: In total, 190 (72%) patients were matched. The median PFS was 5.3 [95% confidence interval (CI) 4.4-6.3] and 4.7 (95% CI 3.2-5.3) months in the nab-PTX + RAM and PTX + RAM groups, respectively [hazard ratio (HR) = 0.76, 95% CI 0.56-1.03, p = 0.07]. The median OS was 11.5 (95% CI 9.2-15.0) and 9.9 (95% CI 8.0-12.7) months, respectively (HR = 0.78, 95% CI 0.56-1.07, p = 0.12). Grade 3 and 4 neutropenia was observed more frequently in the nab-PTX + RAM group (72% vs. 56%, p = 0.03). No treatment-related deaths occurred. CONCLUSIONS: Nab-PTX + RAM exhibited more favorable trends in terms of PFS and OS but was more myelosuppressive than PTX + RAM. As neutropenia is commonly manageable toxicity, nab-PTX + RAM presents a treatment alternative for AGC. Further studies including randomized, controlled studies are warranted.


Assuntos
Nanopartículas , Neoplasias Gástricas , Paclitaxel Ligado a Albumina/uso terapêutico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Recidiva Local de Neoplasia/etiologia , Paclitaxel , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Resultado do Tratamento
12.
Langmuir ; 38(6): 2014-2025, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35099972

RESUMO

Protein-bound paclitaxel has been developed clinically as one of the most successful chemotherapy drugs for the treatment of a wide variety of cancers. However, these medications, due to their nanoscale properties, may often induce capillary blocking while migrating through minute blood vessels. Considering the detrimental impact of this restriction, we investigated the transport of protein-bound paclitaxel, Paclicad, in a 7 µm microchannel mimicking the identical mechanical confinement of the blood capillaries. The drug was reported to migrate through a constricted microchannel without obstruction at a solution flow rate of 20-50 µL/h. The onset of an agglomeration site was observed at higher flow rates of 70-90 µL/h, while complete capillary obstruction was observed at 100 µL/h. The mobility of the particles was also calculated, and the results suggested that the presence of varying cross-sections affects the mobility of the drug particles. The trajectory of the particle migration was observed to be less tortuous at the higher flow rate, but the tortuous nature appeared to increase with the presence of agglomeration sites in the flow field. The experimental results were also compared with the computational model of the drug particle. The drug particle was modeled both as Newtonian and as an FENE-P viscoelastic drop. The drop interface tracking was done by the VOF method using the open source software Basilisk. The particle displacement was better estimated by both the FENE-P and Newtonian model at a flow rate of 30 µL/h, while deviation was observed at a flow rate of 50 µL/h. The FENE-P model was observed to show higher deformation than the Newtonian model at both flow rates. The experimental results provided better insight into the agglomeration tendency of Paclicad, migrating through a constricted microchannel at higher flow rates. The numerical model could be further employed to understand the more complex intravenous transport of drugs.


Assuntos
Antineoplásicos , Neoplasias , Paclitaxel Ligado a Albumina , Capilares , Humanos , Paclitaxel/farmacologia
13.
BMC Cancer ; 22(1): 56, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022029

RESUMO

BACKGROUND: There is increasing evidence that combination therapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this treatment combination for patients with metastatic soft tissue sarcoma (STS) are currently limited. METHODS: The clinical data of patients with metastatic STS who received nab-paclitaxel plus PD-1 inhibitor (sintilimab) therapy between January 2019 and February 2021 were retrospectively analyzed. The effectiveness and safety of the combined treatment were evaluated in terms of the median progression-free survival (PFS), estimated using the Kaplan-Meier method. The univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and PFS. All statistical analyses were two-sided; P < 0.05 was considered statistically significant. RESULTS: A total of 28 patients treated with nab-paclitaxel plus sintilimab were enrolled in this study. The objective response rate was 25%, the disease control rate was 50%, and the median PFS was 2.25 months (95% CI = 1.8-3.0 months). The most common grade 1 or 2 adverse events (AEs) were alopecia (89.3%; 25/28), leukopenia (25.0%; 7/28), fatigue (21.4%; 6/28), anemia (21.4%; 6/28), and nausea (21.4%; 6/28). The most common grade 3 AEs were neutropenia (10.7%; 3/28) and peripheral neuropathy (10.7%; 3/28). No grade 4 AEs were observed. Among the present study cohort, patients with angiosarcoma (n = 5) had significantly longer PFS (P = 0.012) than patients with other pathological subtypes, including undifferentiated pleomorphic sarcoma (n = 7), epithelioid sarcoma (n = 5), fibrosarcoma (n = 4), synovial sarcoma (n = 3), leiomyosarcoma (n = 2), pleomorphic liposarcoma (n = 1), and rhabdomyosarcoma (n = 1); those who experienced three or more AEs had significantly longer median PFS than those who experienced less than three AEs (P = 0.018). CONCLUSION: Nab-paclitaxel plus PD-1 inhibitor is a promising treatment regimen for advanced STS. Randomized controlled clinical trials are required to further demonstrate its efficacy and optimal application scenario.


Assuntos
Paclitaxel Ligado a Albumina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nanopartículas/uso terapêutico , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/patologia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia
14.
Anticancer Drugs ; 33(2): 214-219, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34620744

RESUMO

Cardia neuroendocrine cancer is a rare malignant tumor. The treatment regimens mainly refer to the small-cell lung cancer diagnosis and treatment guidelines and there is no standard treatment guideline specifically for neuroendocrine cancer. The use of albumin paclitaxel plus carboplatin combined with sintilimab for refractory cardia neuroendocrine carcinoma (NEC) has never been reported. This article reported a case that a 68-year-old man presented with belching without obvious reasons who was diagnosed with refractory cardia NEC by gastroscopy and pathological results. After failure of multi-line therapy including etoposide plus cisplatin as the first-line therapy, surufatinib plus toripalimab as the second-line therapy, FOLFIRI combined with bevacizumab as the third-line therapy, he received three cycles of albumin paclitaxel plus carboplatin combined with sintilimab as the fourth-line therapy and still obtained partial response of good efficiency. After the patient received this treatment regimen, the symptoms of dysphagia disappeared and the change trends of neuron-specific enolase were decreased. The computed tomography (CT) examination after three cycles of treatment was performed to show that the measured lesions have shrunk by more than 30% compared to the baseline CT. Additionally, there were no other adverse events such as nausea, vomiting, and diarrhea, except for grade III bone marrow suppression. At present, the patient is still being treated. This is the first case report that the albumin paclitaxel plus carboplatin combined with sintilimab has achieved good efficacy after failure of multi-line treatment of cardia NEC. It is very necessary to further explore the effectiveness and safety of this regimen in the treatment of NEC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Paclitaxel Ligado a Albumina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores
15.
Ann Pharmacother ; 56(8): 898-909, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34963337

RESUMO

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an innovative form of taxane that has superior antitumor effects; however, the safety profile between nab-paclitaxel and traditional taxanes remains controversial. OBJECTIVE: To determine the burden of adverse events (AEs) in patients with multiple malignancies receiving nab-paclitaxel compared with that in patients receiving traditional taxanes. METHODS: Randomized clinical trials comparing nab-paclitaxel with traditional taxanes (solvent-based paclitaxel [sb-paclitaxel] or docetaxel) in the treatment of primary solid-organ malignancies were included if AEs were reported as an outcome. Statistical analyses were conducted to calculate the summary odds ratio (OR) of the relevant adverse outcomes related to nab-paclitaxel and traditional taxanes. Prespecified subgroup analyses based on intervention and doses, primary tumor sites, and different ethnic groups were also performed. RESULTS: Twelve clinical trials were included in the meta-analysis. Grade 3/4 anemia, thrombocytopenia, and neurotoxicity were more frequent with nab-paclitaxel than with traditional taxanes. Nab-paclitaxel at 100 or 125 mg/m2/w dosage was associated with fewer or similar grade 3/4 specific AEs. Allergy was less common with nab-paclitaxel. The median recovery times of neurotoxicity were 25, 64, and 37 days in patients receiving nab-paclitaxel, sb-paclitaxel, and docetaxel, respectively. Elevated incidences of specific AEs were more common in breast cancer and non-Asian patients than in other malignancies and ethnic groups, respectively. CONCLUSION AND RELEVANCE: Nab-paclitaxel increased the risk of hematologic and non-hematologic AEs in general, but anaphylaxis was less common, and the recovery duration of neurotoxicity was shorter. Weekly administration of nab-paclitaxel at a lower dosage provided better tolerance.


Assuntos
Neoplasias da Mama , Nanopartículas , Paclitaxel Ligado a Albumina/efeitos adversos , Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Docetaxel/uso terapêutico , Feminino , Humanos , Nanopartículas/efeitos adversos , Paclitaxel/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Solventes/uso terapêutico , Taxoides/uso terapêutico
16.
BMC Cancer ; 21(1): 1174, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34727875

RESUMO

BACKGROUND: Visceral metastases account for 48-67% of metastatic breast cancer (MBC) patients and presage a worse overall survival. Previous study suggested potential effect of nab-paclitaxel on patients with visceral metastases subgroups. This phase II trial was conducted to explore the efficacy and safety of nab-paclitaxel in such a high-risk group of patients. METHODS: In this prospective, single-center, open-label, phase II study, MBC patients with visceral metastases (N = 80) received nab-paclitaxel (Abraxane, 125 mg/m2, D1, D8, D15 every 28 days). RESULTS: The median PFS was 5.1 months (95% CI: 4.2-6.0 months), with an ORR of 33.8% (95% CI 21.3-43.8%) and CBR of 66.2% (95% CI 56.3-75.0%). In univariate analysis, patients with premenopausal status had a trend of better treatment outcome. Multivariate analysis demonstrated non brain metastasis (adjusted HR 0.31, 95% CI 0.12-0.83, P = 0.019) and first line treatment (adjusted HR 0.37, 95% CI 0.17-0.81, P = 0.013) as independent predictors of longer PFS. The overall safety was acceptable with most common treatment-related, grade ≥ 3 toxicities of neutropenia (16.3%) and sensory neuropathy (3.7%). CONCLUSIONS: This phase II trial documented satisfactory efficacy and safety of nab-paclitaxel in MBC patients with visceral metastases, providing evidence for relative clinical practice. Patients in first line therapy had better treatment outcome. For patients with premenopausal status or brain metastasis, further alternatives (for example, combined chemotherapy or targeting therapy) might be required. This study also demonstrated the efficacy and safety of 125 mg/m2 nab-paclitaxel among Asian patients. TRIAL REGISTRATION: This research is registered under clinicaltrials.gov (NCT02687490, February 22, 2016).


Assuntos
Paclitaxel Ligado a Albumina/uso terapêutico , Albuminas/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/uso terapêutico , Vísceras , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/efeitos adversos , Análise de Variância , Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias da Mama/química , Neoplasias da Mama/patologia , China , Intervalos de Confiança , Feminino , Humanos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Paclitaxel/efeitos adversos , Pré-Menopausa , Intervalo Livre de Progressão , Estudos Prospectivos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia
17.
Biomaterials ; 278: 121140, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34634661

RESUMO

The in vivo fate of nanoformulated drugs is governed by the physicochemical properties of the drug and the functionality of nanocarriers. Nanoformulations such as polymeric micelles, which physically encapsulate poorly soluble drugs, release their payload into the bloodstream during systemic circulation. This results in three distinct fractions of the drug-nanomedicine: encapsulated, protein-bound, and free drug. Having a thorough understanding of the pharmacokinetic (PK) profiles of each fraction is essential to elucidate mechanisms of nanomedicine-driven changes in drug exposure and PK/PD relationships pharmacodynamic activity. Here, we present a comprehensive preclinical assessment of the poly (2-oxazoline)-based polymeric micelle of paclitaxel (PTX) (POXOL hl-PM), including bioequivalence comparison to the clinically approved paclitaxel nanomedicine, Abraxane®. Physicochemical characterization and toxicity analysis of POXOL hl-PM was conducted using standardized protocols by the Nanotechnology Characterization Laboratory (NCL). The bioequivalence of POXOL hl-PM to Abraxane® was evaluated in rats and rhesus macaques using the NCL's established stable isotope tracer ultrafiltration assay (SITUA) to delineate the plasma PK of each PTX fraction. The SITUA study revealed that POXOL hl-PM and Abraxane® had comparable PK profiles not only for total PTX but also for the distinct drug fractions, suggesting bioequivalence in given animal models. The comprehensive preclinical evaluation of POXOL hl-PM in this study showcases a series of widely applicable standardized studies by NCL for assessing nanoformulations prior to clinical investigation.


Assuntos
Antineoplásicos Fitogênicos , Paclitaxel , Paclitaxel Ligado a Albumina , Animais , Linhagem Celular Tumoral , Portadores de Fármacos , Isótopos , Macaca mulatta , Micelas , Ratos , Roedores , Equivalência Terapêutica
18.
Zhonghua Zhong Liu Za Zhi ; 43(10): 1114-1121, 2021 Oct 23.
Artigo em Chinês | MEDLINE | ID: mdl-34695904

RESUMO

Objective: To observe the efficacy and safety of albumin-bound paclitaxel in the treatment of metastatic breast cancer. Methods: Multi-center data of patients who accepted single-drug albumin-bound paclitaxel or combination regimens from 2013 to 2019 were collected and the efficacy and safety were evaluated. Kaplan-Meier method was used for survival analysis, while Log-rank test was used to compare the survival rates. Results: A total of 203 advanced breast cancer cases were enrolled. The median progression-free survival time (PFS) lasted for 4 months, the median overall survival(OS)was 14 months, objective response rate (ORR) was 36.0% while the disease control rate (DCR) was 81.3%. The ORRs of Luminal, human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative breast cancer patients underwent albumin-bound paclitaxel treatment were 37.3%, 45.5% and 31.0%, respectively, the DCRs were 85.5%, 68.2% and 78.9%, respectively. The OS of patients with relapse or metastasis who accepted less than two and more than two chemotherapy regimens were 22 months and 11 months (P<0.000 1), the ORRs were 44.9% vs 30.4%, DCRs were 87.2% vs 77.6% (P=0.018). The ORR and DCR of patients who accepted traditional paclitaxel treatment before the albumin-bound paclitaxel treatment were 35.8% and 82.1%, respectively. The common adverse reaction of these patients was numbness of limbs, which incidence rate was 64.5% (131/203), and 61.1% (124/203) were degree 1 to 2. Other adverse reactions including decreased white blood cells, which incidence rate was 56.1% (114/203); nausea and vomit, which incidence rate was 36.9% (75/203); anemia, which incidence rate was 21.2% (43/203); decreased platelet, which incidence rate was 18.7% (38/203); hepatic dysfunction, which incidence rate was 18.2% (37/203). Conclusions: Albumin-bound paclitaxel single or combination regimen is still significant efficient for various molecular subtypes of breast cancer patients or patients with traditional paclitaxel resistance or multi-line chemotherapy failure. Early usage has better prognosis, controllable adverse reaction and prominent clinical application value.


Assuntos
Paclitaxel Ligado a Albumina , Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Recidiva Local de Neoplasia , Paclitaxel , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
19.
Trials ; 22(1): 568, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446057

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, and multimodal strategies, such as surgery plus neoadjuvant chemotherapy (NAC)/adjuvant chemotherapy, have been attempted to improve survival in patients with localized PDAC. To date, there is one prospective study providing evidence for the superiority of a neoadjuvant strategy over upfront surgery for localized PDAC. However, which NAC regimen is optimal remains unclear. METHODS: A randomized, exploratory trial is performed to examine the clinical benefits of two chemotherapy regimens, gemcitabine plus S-1 (GS) and gemcitabine plus nab-paclitaxel (GA), as NAC for patients with planned PDAC resection. Patients are enrolled after the diagnosis of resectable or borderline resectable PDAC. They are randomly assigned to either NAC regimen. Adjuvant chemotherapy after curative resection is highly recommended for 6 months in both arms. The primary endpoint is tumor progression-free survival time, and secondary endpoints include the rate of curative resection, the completion rate of protocol therapy, the recurrence type, the overall survival time, and safety. The target sample size is set as at least 100. DISCUSSION: This study is the first randomized phase II study comparing GS combination therapy with GA combination therapy as NAC for localized pancreatic cancer. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000021484 . This trial began in April 2016.


Assuntos
Adenocarcinoma , Nanopartículas , Neoplasias Pancreáticas , Paclitaxel Ligado a Albumina/uso terapêutico , Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/análogos & derivados , Proteínas de Ligação ao GTP/uso terapêutico , Humanos , Proteínas de Membrana , Terapia Neoadjuvante/efeitos adversos , Paclitaxel , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Prospectivos
20.
Drug Deliv ; 28(1): 1067-1079, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34109887

RESUMO

BACKGROUND: Combination of the prodrug technique with an albumin nano drug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. METHODS: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA). RESULTS: Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin nanoparticles (Nab-PTX-PA) remained in the tumor for a longer time post-injection. Compared with saline and paclitaxel albumin nanoparticles (Abraxane®), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs, and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organs, and it inhibited tumor cell proliferation more effectively as compared with commercial paclitaxel albumin nanoparticles. CONCLUSIONS: This carrier strategy for small molecule drugs is based on naturally evolved interactions between long-chain fatty acids (LCFAs) and Human Serum Albumin (HSA), demonstrated here for PTX. Nab-PTX-PA shows higher antitumor efficacy in vivo in breast cancer models. On the whole, this novel injectable Nab-PTX-PA has great potential as an effective drug delivery system in the treatment of breast cancer.


Assuntos
Paclitaxel Ligado a Albumina/farmacologia , Antineoplásicos/farmacologia , Paclitaxel Ligado a Albumina/administração & dosagem , Paclitaxel Ligado a Albumina/efeitos adversos , Paclitaxel Ligado a Albumina/farmacocinética , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Proliferação de Células , Química Farmacêutica , Portadores de Fármacos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Feminino , Camundongos , Camundongos Endogâmicos ICR , Nanopartículas , Tamanho da Partícula , Distribuição Aleatória , Propriedades de Superfície
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