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Background/aim: The efficacy of cytotoxic chemo-therapy has been reported to improve after immune checkpoint inhibitor (ICI) administration. We previously conducted a multicenter prospective clinical study to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) after ICI treatment. In that study, some patients showed a long-term response to nab-PTX, which is not usually observed with single-agent chemotherapy. The present study aimed to evaluate the clinical characteristics of these patients., Patients and Methods: We retrospectively analyzed updated data from 29 patients enrolled in our clinical study who received nab-PTX monotherapy after ICI treatment. We defined a "long-term responder" as a patient who achieved a 1-year progression-free survival (PFS)., Results: Among the 29 patients, 10 (34.5%) were long-term responders, two of whom achieved a 5-year PFS. A key difference between long-term and non-long-term responders was that the long-term responders had a significantly higher number of patients with Eastern Cooperative Oncology Group-performance status of 0 (70.0% versus 10.5%; p=0.002). Furthermore, median cycles of previous ICIs and median treatment cycles were significantly higher in long-term responders than in non-long-term responders (8 cycles versus 3 cycles; p=0.03) (5.9 months versus 2.0 months; p=0.02). In the 10 long-term responders, six patients required at least a one-stage dose reduction owing to adverse events, and four patients required a two-stage dose reduction., Conclusion: Nab-PTX administration after ICI treatment may elicit a long-term response. A long-term response can be achieved even with a dose reduction due to adverse events., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The neoadjuvant therapeutic effects of various chemotherapeutic drugs on gastric cancer have reached the corresponding plateau. Whether the combination of sindilizumab and albumin-bound paclitaxel+oxaliplatin+S-1 chemotherapy (SAPO-S1 therapy) regimen can bring better efficacy and observe the incidence of adverse reactions in the neoadjuvant treatment of Gastric Cancer (GC) may be the direction of our research. This study aimed to evaluate the efficacy of S1 chemotherapy regimen combined with multiple chemotherapy drugs sindilizumab (PD-1 inhibitor), albumin-bound paclitaxel and oxaliplatin) for neoadjuvant therapy in locally advanced Gastric Cancer (LA-GC). The patients were given 4 cycles of sindilizumab combined with albumin paclitaxel+oxaliplatin+S-1 chemotherapy (SAPO-S1) before surgery. The R0 resection rate, surgical complications, pathologic complete response, complete pathologic response (pCR) the main pathological response rates (residual tumor cells≤10%, major pathological response) were observed. MPR and postoperative pathological tumor regression grade (TRG), using the response evaluation criteria in solid tumors (RECIST1.1) to evaluate the efficacy of new adjuvant therapy and record the short-term adverse events (adverse event, AE) of patients after medication to evaluate safety. The overall response rate (ORR) was achieved to 53.3% and disease control rate (DCR) was achieved in 28 patients (93.3%), and the descending phase was achieved in 17 patients (56.7%). The tumor resolution grades of TRG 0, TRG 1, TRG 2 and TRG 3 were 16.7%, 13.3%, 43.3% and 16.7%, respectively. The pCR rate was 16.7%, the MPR rate was 30.0%, and the R0 resection rate was 90.0%. In addition, SAPO-S1 therapy has fewer side effects. Overall, SAPO-S1 therapy has a good therapeutic effect and safety in LA-GC.

Background: Neoadjuvant chemotherapy may be considered for patients with ovarian cancer (OC) whose tumors are deemed unlikely to be completely cytoreduced to no gross residual disease (R0) or who are poor surgical candidates. This Ib/II study was designed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin as neoadjuvant chemotherapy for stages III-IV, unresectable OC., Methods: Eligible patients with stage III-IV, unresectable OC were enrolled in this phase Ib/II study. All patients received neoadjuvant nab-paclitaxel (260 mg/m 2 , day 1, every 3 weeks) plus carboplatin (AUC 5, day 1, every 3 weeks) for 3 cycles before surgery, followed by 3-6 cycles of adjuvant chemotherapy. The phase Ib primary endpoint was safety; the phase II primary endpoint was the R0 resection rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety (for all populations)., Results: Sixty-two patients were enrolled and were given neoadjuvant therapy treated between October 2019 and December 2020, of whom 9 were in the phase Ib portion and 53 in the phase II portion. A total of 53 patients underwent surgery with an R0 resection rate of 73.6% (95% CI, 59.7-84.7%). With a median follow-up of 17.5 (range 0.7-36.7) months, for all patients, the best ORR was 83.9% (95% CI, 71.7-92.4%) with 47 partial responses, the median PFS was 18.6 (95% CI, 13.8-23.3%) months, and median OS was not reached. During the neoadjuvant chemotherapy, treatment-related adverse events (TRAEs) of any grade occurred in 91.9% (57/62) of all patients. The most common hematologic TRAEs were neutropenia (55/62, 88.7%), and non-hematologic toxicity was alopecia (36/62, 58.1%). Forty-nine patients (79.0%) experienced at least one grade 3-4 TRAEs, with the most common was neutropenia (44/62, 71.0%). Besides, delays in neoadjuvant chemotherapy and surgery due to AEs were observed in 9 (1 in phase Ib; 8 in phase II) and 7 (phase II) patients, respectively., Conclusions: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant chemotherapy nab-paclitaxel plus carboplatin in stage III-IV, unresectable OC. In addition, AEs resulting in chemotherapy and surgery delays should be cautiously considered in this clinical setting., Trial Registration: ClinicalTrials.gov, ChiCTR1900026893. Registered at 25 October 2019., (© 2024. The Author(s).)

Purpose: At present, albumin-bound paclitaxel combined with platinum is the standard first-line treatment option for advanced esophageal cancer (EC). However, following a hospitalization surge, clinicians may prefer to use albumin-bound paclitaxel as a single dose. The present study aimed to investigate the survival of patients with advanced EC when treated with single or fractionated doses of albumin-bound paclitaxel., Methods: We collected survival data of patients with advanced first-line EC who had used albumin-bound paclitaxel with or without other treatment regimens from January 2018 to September 2023 at the Harbin Medical University Cancer Hospital and the Shanxi Province Cancer Hospital. The patients were divided into two groups according to the frequency and dose of albumin-bound paclitaxel administration, namely the abraxane fractional administration group (A group, 27 patients) and the abraxane single administration group (B group, 182 patients)., Results: The median progression-free survival (PFS) was 9.0 months in both groups ( p  = 0.35), and the median overall survival (OS) was 21.0 months in A group and 18.0 months in B group ( p  = 0.61). The objective response rate was 37% in A group and 25% in B group ( p  = 0.314), and the disease control rate was 89% in A group and 83% in B group ( p  = 0.580). The incidence of grade 3 or higher treatment-related adverse events was 15% in both groups., Conclusion: Albumin-bound paclitaxel treatments showed no statistically significant differences in the PFS or OS. They were considered safe, whether administered as a single dose or in fractionated doses., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Effective treatment strategies for second-line therapy in extensive-stage small cell lung cancer (ES-SCLC) are currently lacking. For this reason, we collected and recorded efficacy and safety data from patients with ES-SCLC who had disease progression after first-line treatment and received albumin-bound paclitaxel, anlotinib, and immunotherapy. Preliminary data showed an objective response rate of 37.78%. Median progression-free survival and overall survival were 5 months and 10 months, respectively. Treatment-related adverse events were mostly tolerable. Subgroup analysis indicated that efficacy correlated with the interval from last chemotherapy to treatment initiation and specific drug-related adverse events. Further analysis of immune cell subtypes suggested that the mechanism may involve depletion of immune suppression to activate immune responses synergistically against tumors. With its promising efficacy and manageable adverse effects, this regimen holds potential as a significant option for second-line therapy in ES-SCLC. However, due to the limited sample size, further clinical validation is needed to ascertain its true clinical value.

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/m 2 or 260 mg/m 2 and oxaliplatin 130 mg/m 2 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/m 2 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., (© 2024. The Author(s).)

Purpose: To evaluate the short-term safety of albumin-bound paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) during and after gastric cancer (GC) surgery., Methods: A retrospective analysis of clinical data was conducted for GC surgery patients at Zhongnan Hospital of Wuhan University, from January 2020 to September 2022. The study group (n = 120) received HIPEC and the control group (n = 268) did not receive albumin-bound paclitaxel. Short-term safety indicators including intraoperative complications, hematological toxicity, liver and kidney function, and gastrointestinal function recovery were compared between the two groups., Results: There were no statistically significant differences between the two groups regarding intraoperative complications, hematological toxicity, liver and kidney function, and gastrointestinal function recovery time (P > 0.05 for all). In the study group, patients were further divided into subgroups based on dose and timing. Subgroup analysis revealed no significant differences among the different dose subgroups. However, when focusing on timing subgroups, the postoperative subgroup exhibited significantly higher white blood cell counts and bilirubin levels compared to the intraoperative subgroup, while the intraoperative subgroup had significantly higher bilirubin levels compared to both postoperative and intraoperative plus postoperative subgroups., Conclusion: Albumin-bound paclitaxel demonstrates good safety and tolerability in HIPEC during and after GC surgery, without increasing the risk of intraoperative complications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients., Methods: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically., Results: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients., Conclusions: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Taxanes are the basic components of breast cancer chemotherapy. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) shows improved antitumor effects because of more targeted delivery. However, the effects of nab-paclitaxel have not been systematically studied in patients with metastatic breast cancer (MBC) pretreated with taxanes. Considering the limited treatment options for MBC, this study retrospectively evaluated the clinical efficacy and adverse effects of nab-paclitaxel in patients with taxane-pretreated MBC., Methods: Patients who had previously received taxanes and subsequently received nab-paclitaxel chemotherapy for MBC at Jiangsu Cancer Hospital between October 2014 and April 2022 were included for analysis. The primary end point was progression-free survival (PFS), and the secondary end points were the objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and side effects., Results: A total of 236 female patients with MBC were included. The median PFS was 7.20 months (95% confidence interval [CI], 6.63-7.80 months), and the ORR, DCR, and CBR were 29.55% (95% CI, 23.50%-35.60%), 83.64% (95% CI, 78.70%-88.60%), and 56.36% (95% CI, 49.80%-63.00%), respectively. Following nab-paclitaxel treatment, the median PFS of patients who were sensitive to taxanes during previous treatments was significantly longer than that of patients who were resistant to taxanes (7.57 months vs. 4.43 months, p < .001). The most common adverse events were sensory neuropathy (89.83%), neutropenia (48.73%), leukopenia (46.61%), and anemia (35.59%)., Conclusion: Nab-paclitaxel demonstrated clinical activity in taxane-pretreated patients with MBC. This beneficial effect was observed both in patients who were sensitive and resistant to taxanes during previous treatments. These results suggest nab-paclitaxel as the preferred chemotherapy regimen in patients with MBC, regardless of their sensitivity to taxanes during previous treatments., (© 2024 American Cancer Society.)

Objective: This research aimed to assess the efficacy and safety of pembrolizumab (PBL) combined with albumin-bound paclitaxel (ab-Pac) and nedaplatin (NDP) for advanced esophageal squamous cell carcinoma (ESCC). Methods: A total of 47 ESCC patients were administered PBL or NDP on day 1 and ab-Pac on days 1 and 8, every 21 days for one cycle. Tumor and toxicities were evaluated every two cycles and every cycle, respectively. Results: The objective response rate was 68.1% and the disease control rate was 100%. The median follow-up was 16.7 months; median progression-free and overall survival were 12.6 and 19.9 months, respectively. Conclusion: The combination of PBL with ab-Pac and NDP proved to be an effective and safe treatment regimen for advanced ESCC.

Introduction: Recent studies have suggested enhanced therapeutic effects of subsequent chemotherapy after immune checkpoint inhibitor (ICI) treatment, highlighting the importance of subsequent treatment selection. Nanoparticle albumin-bound paclitaxel (nab-PTX) is commonly used in subsequent chemotherapies; however, its efficacy as a subsequent treatment after ICI treatment has not been reported., Methods: We retrospectively evaluated the efficacy and safety of nab-PTX using two prospective studies that we previously reported. The first study evaluated the efficacy and safety of nab-PTX as a second-line treatment after the failure of the first-line cytotoxic chemotherapy, excluding ICI (study 1; n = 32), and the other as a subsequent treatment after failure of ICI treatment, regardless of treatment line (study 2; n = 29)., Results: The objective response rate was significantly higher in study 2 {55.2% (95% confidence interval [CI]: 28.1-79.6)} than in study 1 (28.1% [95% CI: 13.7-46.7]) (p = 0.04). Although the disease control rate was slightly higher in study 2 (86.2% [95% CI: 65.9-97.0]) than in study 1 (71.9% [95% CI: 53.3-86.3]), there was no significant difference (p = 0.2). The median progression-free survival was significantly longer in study 2 than in study 1 (3.9 months [95% CI: 2.0-5.5] in study 1 vs. 5.6 months [95% CI: 3.0-12.8] in study 2; hazard ratio [HR]: 0.46 [95% CI: 0.27-0.81], p = 0.006). The median overall survival was slightly longer in study 2 despite the greater number of patients who received nab-PTX in late treatment line, but there was no significant difference between study 1 and study 2 (10.9 months [95% CI: 5.1-16.8] in study 1 vs. 11.9 months [95% CI: 7.6-24.8] in study 2; HR: 0.77 [95% CI: 0.46-1.31], p = 0.34). Safety profiles did not differ between the patients in studies 1 and 2., Conclusion: Nab-PTX monotherapy may be an effective subsequent treatment option after ICI treatment., (© 2024 S. Karger AG, Basel.)

Objective: Dose-dense chemotherapy has shown a better prognosis than standard interval chemotherapy in adjuvant settings for high-risk breast cancer. This study aimed to evaluate the efficacy and safety of dose-dense nanoparticle albumin-bound paclitaxel followed by dose-dense epirubicin and cyclophosphamide as neoadjuvant chemotherapy for human epidermal growth factor 2 (HER2)-negative operable breast cancer., Methods: Patients with histologically confirmed stage I-III HER2-negative breast cancer were enrolled in this study. Patients received nanoparticle albumin-bound paclitaxel (260 mg/m2) followed by epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 2 weeks with pegfilgrastim. The primary endpoint was the pathological complete response rate. Patients also underwent prophylactic management for peripheral neuropathy, which involved a combination of cryotherapy, compression therapy using elastic stockings and medications including goshajinkigan., Results: Among the 55 patients enrolled in this study, 13 (23.6%) achieved pathological complete response, of whom 10/26 (38.5%) patients had triple-negative disease and 3/29 (10.3%) had luminal disease. The objective response was observed in 46 (83.6%) patients. Of the 36 patients who were initially planned for mastectomy, 11 (30.6%) underwent breast-conserving surgery after neoadjuvant chemotherapy. The most common grade 3-4 adverse events were myalgia (14.5%), fatigue (12.7%) and elevated transaminase levels (9.1%). No patients experienced febrile neutropenia. Eight (14.5%) patients discontinued treatments due to adverse events., Conclusions: Neoadjuvant dose-dense biweekly nanoparticle albumin-bound paclitaxel followed by dose-dense epirubicin and cyclophosphamide was effective, especially in patients with triple-negative disease, and feasible with pegfilgrastim support., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: There are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study aims to retrospectively evaluate the efficacy of different taxanes on neoadjuvant systemic treatment (NST) in breast cancer., Methods: Patients who were diagnosed with breast cancer and had received integral NST from August 2013 to April 2022 were enrolled. The efficacy was divided into total pathological complete response (total-pCR), breast pathological complete response (breast-pCR), and axillary pathological complete response (axillary-pCR) for in-depth analysis and discussion., Results: The choice of taxane was an independent risk factor for total-pCR and breast-pCR rates. The highest total-pCR and breast-pCR rates were found in the Nab-P group. The difference was not significant among all the taxanes in the axillary-pCR rate., Conclusion: Nab-P significantly improved the total-pCR and breast-pCR rates. It should be the first choice among taxanes in NST for breast cancer., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Background: Temozolomide (TMZ) treatment efficacy in glioblastoma (GBM) patients has been limited by resistance in the clinic. Currently, there are no clinically proven therapeutic options available to restore TMZ treatment sensitivity. Here, we investigated the potential of albumin-bound paclitaxel (ABX), a novel microtubule targeting agent, in sensitizing GBM cells to TMZ and elucidated its underlying molecular mechanism., Methods: A series of in vivo and in vitro experiments based on two GBM cell lines and two primary GBM cells were designed to evaluate the efficacy of ABX in sensitizing GBM cells to TMZ. Further proteomic analysis and validation experiments were performed to explore the underlying molecular mechanism. Finally, the efficacy and mechanism were validated in GBM patients derived organoids (PDOs) models., Results: ABX exhibited a synergistic inhibitory effect on GBM cells when combined with TMZ in vitro. Combination treatment of TMZ and ABX was highly effective in suppressing GBM progression and significantly prolonged the survival oforthotopic xenograft nude mice, with negligible side effects. Further proteomic analysis and experimental validation demonstrated that the combined treatment of ABX and TMZ can induce sustained DNA damage by disrupting XPC and ERCC1 expression and nuclear localization. Additionally, the combination treatment can enhance ferroptosis through regulating HOXM1 and GPX4 expression. Preclinical drug-sensitivity testing based on GBM PDOs models confirmed that combination therapy was significantly more effective than conventional TMZ monotherapy., Conclusion: Our findings suggest that ABX has the potential to enhance TMZ treatment sensitivity in GBM, which provides a promising therapeutic strategy for GBM patients., (© 2023. The Author(s).)

Objective The effect of sarcopenia on the prognosis of patients undergoing chemotherapy for unresectable pancreatic ductal adenocarcinoma remains largely unexplored. In this retrospective study, we investigated the relationship between sarcopenia and the prognosis of patients receiving first-line nanoparticle albumin-bound paclitaxel plus gemcitabine for unresectable pancreatic ductal adenocarcinoma. Methods We enrolled 251 patients with unresectable metastatic or locally advanced pancreatic ductal adenocarcinoma who had received chemotherapy between January 2015 and December 2020 at Kitasato University Hospital. Univariate and multivariate analyses were performed using the stratified Cox proportional hazards model to determine variables significantly associated with the progression-free and overall survival. Propensity score matching was performed to mitigate selection bias effects. Results In the propensity score-matched cohort, the progression-free and overall survival were not significantly different between the sarcopenia and non-sarcopenia groups (p=0.335, and 0.679 respectively). The skeletal muscle index decreased by 4.4% and 6.5% in the sarcopenia and non-sarcopenia groups, respectively, during the early treatment phase (p=0.084). There were no significant differences between groups with regard to major adverse events or drug toxicity occurrences. Both the progression-free and overall survival were significantly shorter in the skeletal muscle index loss group than in the non-skeletal muscle index loss group (p=0.026 and 0.045, respectively). Conclusion Skeletal muscle index loss during the initial treatment phase may be an early marker for the long-term prognosis of patients receiving nanoparticle albumin-bound paclitaxel plus gemcitabine as first-line treatment for unresectable pancreatic ductal adenocarcinoma.

Objectives: The advent of effective chemotherapy regimens has increased the use of neoadjuvant multiagent chemotherapy in pancreatic cancer. However, the effect of tumor downstaging with neoadjuvant treatment on survival is unclear., Methods: Retrospective study included all resected patients with pancreatic adenocarcinoma who underwent neoadjuvant chemotherapy with FOLFIRINOX or gemcitabine/Abraxane. Downstaging was quantified using (1) difference between presenting AJCC clinical and final pathologic stage and (2) College of American Pathologists (CAP) Tumor Regression Grading Schema., Results: Eighty-seven patients met inclusion criteria. FOLFIRINOX was the most common regimen, 63.2% vs 21.8%. Change in regimen occurred in 15% of patients. Downstaging based on a difference in AJCC stage group occurred in only 4.6%. In contrast, 45.2% were classified as downstaged by the CAP Tumor Regression of 0-2. Downstaging was similar for FOLFIRINOX gemcitabine/Abraxane (64.7 vs 53.6, P = .12) using the CAP criteria. On univariate analysis, treatment regimen (gemcitabine/Abraxane vs FOLFIRINOX, median survival 27 vs 29 mo; HR 1.57, P = .2) had similar survival. Downstaging by the AJCC stage was not associated with improved survival (HR 1.51, P = .4). However, there was a survival benefit for those downstaged by the CAP Tumor Regression Grading Schema, the median survival of 41 mo vs 25 mo; HR 3.05, P = .009. Improved survival 3.32 (1.35-8.16), P = .009) was maintained on multivariate analysis., Conclusion: Survival is significantly improved in those downstaged, as assessed by the CAP Tumor Regression Schema. Downstaging is an important prognostic variable that can help with joint decision making for clinicians and patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

There is substantial evidence that albumin-bound paclitaxel (nab-paclitaxel) is effective and safe for the treatment of breast, lung and pancreatic cancers. However, it can still cause adverse effects by affecting cardiac enzymes, hepatic enzyme metabolism and blood routine related indicators, which affects the use of chemotherapy for a full course of treatment. However, there are no relevant clinical studies to systematically observe the effects and dynamics of albumin-bound paclitaxel on cardiac enzymes, liver enzyme metabolism, and routine blood-related indices. The purpose of our study was to determine the levels of serum creatinine (Cre), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), white blood cells (WBC) and hemoglobin (HGB) in cancer patients treated with albumin-conjugated paclitaxel. This study retrospectively analyzed 113 patients with cancer. Patients who had received two cycles of nab-paclitaxel 260 mg/m 2 (administered intravenously on days 1, 8, and 15 of each 28-day cycle) were selected. Serum Cre, AST, ALT, LDH, CK, and CK-MB activities, WBC counts, and HGB levels were measured before and after treatment with two cycles. Fourteen cancer types were analyzed. The distribution of cancer types in patients was mainly concentrated in lung, ovarian, and breast cancer. Nab-paclitaxel treatment markedly decreased Cre, AST, LDH, and CK activities in the serum and WBC counts and HGB levels, respectively. Serum Cre and CK activities and HGB levels were remarkably downregulated at baseline compared to healthy controls. Patients receiving nab-paclitaxel treatment cause metabolic disorders in tumor patients by reducing the decrease of Cre, AST, LDH, CK, CK-MB, WBC and HGB indexes, thus inducing the occurrence of cardiovascular events, hepatotoxic events and fatigue and other symptoms. Therefore, for tumor patients, although receiving nab-paclitaxel improves the anti-tumor effect, it is still necessary to closely monitor the changes of related enzymatic and routine blood indicators, so as to detect and intervene at an early stage., (© 2023. The Author(s).)

This study aimed to compare the efficacy of neoadjuvant systemic therapy (NST) with solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel in human epidermal growth factor receptor 2 (HER2)-low-positive and HER2-zero breast cancers. A total of 430 patients receiving 2-weekly dose-dense epirubicin and cyclophosphamide (EC) followed by 2-weekly paclitaxel (Sb-P, Lps-P, or Nab-P), or 3-weekly EC followed by 3-weekly docetaxel for NST were enrolled in the study. In HER2-low-positive patients, the pathological complete response (pCR) rate in Nab-P group was significantly higher than that in the other three paclitaxel groups (2.8 % in Sb-P group, 4.7 % in Lps-P group, 23.2 % in Nab-P group and 3.2 % in docetaxel group, p < 0.001). In HER2-zero patients, the pCR rate did not differ significantly among the four paclitaxel groups (p = 0.278). The NST regimen containing Nab-P could be considered a promising treatment option in HER2-low-positive breast cancer., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Breast cancer is the most common malignant tumor of women, which seriously threatens women's health. Albumin-bound paclitaxel is the basic chemotherapy drug for breast cancer treatment. We can promote reasonable clinical medication and improve patients' quality of life by standardizing chemotherapy plans, rationally optimizing treatment strategy and managing adverse reactions of albumin-bound paclitaxel. In order to standardize the clinical application of albumin-bound paclitaxel in breast cancer, Chinese Medical Doctor Association Oncologist Branch Breast Cancer Group and International Medical Exchange Branch of China Anti-Cancer Association consulted guidelines and the latest evidence-based evidences and formulated Chinese expert consensus of albumin-bound paclitaxel in the treatment of breast cancer to provide reference for clinical diagnosis and treatment of breast cancer. The consensus mainly introduces the clinical application strategies and evidence-based evidences of albumin-bound paclitaxel in advanced therapy, neoadjuvant therapy and adjuvant therapy of breast cancer. Among them, the regimens containing albumin-bound paclitaxel are the better recommended regimens for preoperative neoadjuvant and advanced rescue therapy of breast cancer. However, there is little evidence in adjuvant therapy, so it is recommended to use albumin-bound paclitaxel cautiously. We also invited breast cancer clinical experts to vote on some controversial issues, including but not limited to the usage and dosage of albumin-bound paclitaxel, combined medication and management of peripheral neuropathy, and formed consensus recommendations for the reference of breast cancer clinical workers.

This study was designed to observe the efficacy and safety of albumin-bound paclitaxel plus nedaplatin as neoadjuvant therapy in patients with esophageal squamous cell carcinoma (ESCC). From April 2019 to Dec 2020, patients with ESCC who underwent Mckeown surgery at our center were analyzed retrospectively. All patient received 2 to 3 cycles of albumin-bound paclitaxel combined with nedaplatin before surgery, tumor regression grade (TRG) and American National Cancer Institute Common Toxicity Criteria version 5.0 were used to evaluate its efficacy and safety. TRG grades from TRG 2 to TRG 5are considered effective in chemotherapy, TRG 1 stands for pathological complete response (pCR). A total of 41 patients were included in this study. All patients achieved R0 resection. According to the TRG classification, the number of patients assessed for TRG 1-TRG 5 were: 7 cases, 12 cases, 3 case, 12 cases and 7 cases. Its objective response rate and pCR were 82.9% (34/41) and 17.1% (7/41), respectively. We found that hematological toxicity is the most common adverse events of this regimen, with an incidence of 24.4%, followed by digestive tract reactions, with an incidence of 17.1%. Hair loss, neurotoxicity and hepatological disorder are the others, their incidence was 12.2%, 7.3%, and 2.4%; and chemotherapy related deaths were no found. Notably, 7 patients achieved pCR without recurrence or death. Survival analysis showed that patients with pCR may have longer disease-free survival (P = .085) and overall survival (P = .273), although the difference was not statistically significant. As neoadjuvant therapy for patients with ESCC, albumin-bound paclitaxel combined with nedaplatin has a higher pCR rate and less side effects. It is a reliable choice for ESCC patients as neoadjuvant therapy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the impact of Xihuang Capsule combined with albumin-bound paclitaxel on the treatment of stage III breast cancer and T cell subsets, survival rate and adverse reactions. Totally 200 patients with stage III breast cancer were evenly randomized into control group (albumin-bound paclitaxel for chemotherapy) and observation group (Xihuang Capsules for adjuvant therapy based on the treatment of the control group). The RR and DCR of the observation group was markedly higher as compared to the control group (66.7% vs 28.6%; 80.9% VS 47.6%) (all P <0.05). After 4 weeks of treatment, the CD8 + in the two groups decreased, while CD3+ and CD4+ increased, and the change in observation group was more significant (all P<0.05). The observation group exhibited a better half-year, 1-year, 1.5-year and 2-year survival rates compared to the control group (81.0% vs 71.4%, 71.4% vs 57.1%, 57.1% vs 33.3% and 42.9%vs 19.0%) (all P<0.05). Adding Xihuang Capsule to adjuvant therapy with albumin paclitaxel chemotherapy benefits the patient's immunity and survival rate, with good efficacy and safety profiles.

Cerium oxide nanoparticles (CeONPs) displayed cytotoxic properties against some cancer cells. However, there is very limited data about the possible antitumoral potential of them in breast cancer cells when used alone and/or together with a chemotherapeutic drug. We investigated the effects of CeONPs alone or in combination with paclitaxel (PAC) on healthy or carcinoma breast cells. After human breast cancer cells (MCF-7) treated with CeONPs alone or together with PAC for 24, 48, and 72 h, the effects of CeONPs on cell viability, apoptosis, migration, and adhesion were investigated. All cell viability and IC50 values of CeONPs and PAC treatments in healthy breast cells (HTERT-HME1) were higher than MCF-7 cells. They showed higher cytotoxicity against MCF-7 cells. CeONPs (10, 20, and 30 mM) and/or abraxane (AB) (2 μM) significantly decreased cell viability values in MCF-7 cells. All CeONPs concentrations increased the number of apoptotic MCF-7 cells. CeONPs (20 and 30 mM) alone or in combination with AB for 72 h treatment also significantly increased the apoptosis in compared to AB alone. CeONPs and/or AB can significantly inhibit the migratory ability of breast cancer cells. The migration rates in co-treated groups with CeONPs and AB were lower than CeONPs treatments. Higher concentrations of CeONPs alone or together with AB inhibited cell adhesion. Our results showed CeONPs can increase cytotoxicity and apoptosis and decrease cell migration and cell adhesion when used alone or together with AB. Therefore, combination of chemotherapeutics with CeONPs may provide a good strategy against cancer., (© 2022 Wiley Periodicals LLC.)

The disorganized vasculatures in tumors represent a substantial challenge of intratumor nanomedicine delivery to exert the anticancer effects. Herein, we rationally designed a glutathione (GSH)-activated nitric oxide (NO) donor loaded bioinspired lipoprotein system (NO-BLP) to normalize tumor vessels and then promote the delivery efficiency of sequential albumin-bound paclitaxel nanoparticles (PAN) in tumors. NO-BLP exhibited higher tumor accumulation and deeper penetration versus the counterpart liposomal formulation (NO-Lipo) in 4T1 breast cancer tumors, thus producing notable vascular normalization efficacy and causing a 2.33-fold increase of PAN accumulation. The sequential strategy of NO-BLP plus PAN resulted in an 81.03% inhibition of tumor growth in 4T1 tumors, which was better than the NO-BLP monotherapy, PAN monotherapy, and the counterpart NO-Lipo plus PAN treatment. Therefore, the bioinspired lipoprotein of NO-BLP provides an encouraging platform to normalize tumor vessels and promote intratumor delivery of nanomedicines for effective cancer treatment.

Over the past decade, the dose of nanoparticles given to solid tumors has remained at a median of 0.7% of the injected dose. Most nanoparticles are trapped in a mononuclear phagocyte system (MPS), of which 85% are Kupffer cells. In our study, threshold doses of bovine serum albumin (BSA) nanoparticles were investigated for the uptake of Kupffer cells in vitro and in vivo. The antitumor effect and safety of albumin-bound paclitaxel (ABP) were improved by using threshold doses of BSA nanoparticles. We found a threshold dose of 20,000 nanoparticles per macrophage uptake in vitro and a saturation dose of 0.3 trillion nanoparticles in tumor-bearing mice. In vivo efficacy and safety evaluations demonstrated that the threshold doses of blank BSA nanoparticles could significantly improve the efficacy and safety of ABP against tumors compared with ABP alone. In this study, the delivery efficiency of ABP was improved by using blank nanoparticles to saturate Kupffer cells, which provided a new approach to studying the Kupffer cell saturation threshold and thus a new scheme for improving the curative effect of ABP.

Aim: To investigate the efficacy and safety of preoperative neoadjuvant therapy (PD-1 inhibitor plus nab-PTX and nedaplatin) for resectable stage III lung squamous cell carcinoma (SCC) patients., Methods: Patients with locally advanced lung SCC (stage IIIA, IIIB) who received PD-1 inhibitor combined with nab-PTX and NED between February 2019 and June 2021 in Weihai Municipal Hospital were included and underwent surgical treatment 4 weeks after 2-4 cycles neoadjuvant therapy. The rate of resection R0, the effective rate, the complete pathological remission rate (pCR) and the rate of major pathological remission (MPR) were observed., Results: A total of 14 initially unresectable male patients with lung SCC were included and received neoadjuvant treatment after evaluation. Nine out of 14 patients (64.3%) experienced treatment-related adverse events (TRAE), among which 8 (57.1%) experienced grade (G) I-II TRAEs including nausea, vomiting, fatigue, constipation, elevated ALT and AST, hyperthyroidism, hypothyroidism, rash, granulocytopenia, and thrombocytopenia, and 1 (7.1%) experienced grade III-V TRAEs (G), including granulocytopenia and atelectasis. Thirteen patients (92.86%) achieved RECIST-assessed partial remission (PR), while 1 patient (7.14%) achieved stable disease (SD) on imaging assessment after neoadjuvant treatment and continued to be progression-free for 26 months. Of the 11 patients who underwent resection, all were alive and recurrence/progression-free. MPR and pCR were observed in 2 (18.18%) and 9 (81.82%), respectively. IHC results exhibited that all NSCLC patients exhibited positive PD-L1 expression (9/14, TPS ≥50% or greater; 5/14, 1% < TPS < 50%). Two were negative for ALK, EGFR, and ros-1, and the rest were not examined for driver oncogene mutation., Conclusion: The neoadjuvant therapy of the PD-1 inhibitor combined with nab-PTX and NED demonstrated remarkable therapeutic efficacy and good safety on stage III lung SCC without increasing the risk of TRAE, mortality and surgery-related complications, or impede surgery feasibility., Competing Interests: The authors declare no conflicts of interest in this work., (© 2022 Xu et al.)

In this study, a novel carboxymethyl dextran (CMD)-based dual drug delivery system that delivering two water insoluble drugs to tumor sites was developed and evaluated for anticancer activities. Paclitaxel (PTX) and docosahexaenoic acid (DHA) were covalently coupled with CMD to generate CMD-DHA-PTX conjugate S and conjugate L with different linkers containing amino acids Gly-Gly or Lys-Gly-Gly, respectively. Both conjugates possessed high PTX loading contents and enhanced water solubility, as well as the ability of being self-assembled into nanoparticles with the nanoparticle size ranged from 88.7 nm to 94.7 nm. These two conjugates released free PTX continuously in plasma and cancer cells. The conjugate S exhibited improved pharmacokinetic parameters and higher distribution extent in tumor sites than the parent PTX, Abraxane and the conjugate L. The antitumor efficacy of these two conjugates outperformed parent PTX formulation and Abraxane in nude mice bearing breast cancer cells MCF-7. More importantly, the conjugate S treatment eliminated all the xenograft tumors without causing any mice body weight loss in mice model. This study revealed that the dextran-based dual drug conjugates may represent an effective and innovative way to deliver anticancer agents to a variety of tumors., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Numerous studies have concentrated on neoadjuvant therapies for treating triple-negative breast cancer (TNBC) that improve the pathological complete response (pCR) rate but remain controversial. We conducted a network meta-analysis (NMA) to objectively explore the efficacy and safety of different neoadjuvant regimens., Methods: Phase II/III randomized clinical trials that compared different neoadjuvant therapies for TNBC were included. NMA and pairwise meta-analysis were performed using WinBUGS (version 1.4.3) and Review Manager 5.3., Results: Forty-four studies with 8459 patients met the eligibility criteria. The NMA of pCR showed that programmed cell death Protein-1 and programmed cell death Ligand-1 inhibitors (PD-1/PD-L1), bevacizumab (Bev), zoledronic acid (ZOL), and platinum salts plus poly polymerase inhibitors (Pt+PARPi) may be favorable for TNBC neoadjuvant therapy. Chemotherapy combined with platinum salts or nanoparticle albumin-bound paclitaxel (Nab-p) has additional beneficial effects. However, neo-type drugs may also have increased toxicity., Conclusion: PD-1/PD-L1, Bev, ZOL, and Pt+ PARPi-containing regimens improved the pCR rate compared to traditional chemotherapy, including anthracyclines and taxanes. Chemotherapy with platinum salts or Nab-p improved the pCR rate. Nevertheless, the balance between efficacy and toxicity should be evaluated rigorously. PD-1/PD-L1-containing regimens appear to be the most favorable for TNBC neoadjuvant therapy, with good efficacy and tolerance.

ABCC10/MRP7, an ATP-binding cassette (ABC) transporter, has been implicated in the extracellular transport of taxanes. Our group reported that the ABCC10 single nucleotide polymorphism (SNPs), rs2125739, influences docetaxel cytotoxicity in lung cancer cell lines as well as its side effects in clinical practice. In this study, we investigated whether the rs2125739 variant could affect paclitaxel (PTX) cytotoxicity in lung cancer cell lines. We also investigated the effect of rs2125739 on the efficacy and safety of nanoparticle albumin-bound PTX (nab-PTX) in clinical practice. The association between rs2125739 genotypes and the 50% inhibitory concentration (IC 50 ) of PTX was investigated in 18 non-small cell lung cancer (NSCLC) cell lines, HeLa cells, and genome-edited HeLa cells. Next, blood samples from 77 patients with NSCLC treated with carboplatin plus nab-PTX were collected and analyzed for six SNPs, including rs2125739. The clinical outcomes among the different genotype groups were evaluated. In NSCLC cell lines, HeLa cells, and genome-edited HeLa cells, the IC 50 was significantly higher in the ABCC10 rs2125739 T/T group than in the T/C and C/C groups. In 77 patients with NSCLC, there were no significant differences in clinical outcomes between the T/T and T/C groups. However, the rs2125739 T/T genotype was associated with a higher frequency of Grades 3/4 neutropenia. In contrast, there was no association between other SNPs and clinical efficacy or neutropenia. Our results indicate that the ABCC10 rs2125739 variant is associated with neutropenia in response to nab-PTX treatment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

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., (© 2022. The Author(s).)

Background: Among total cancer deaths, esophageal cancer ranks sixth in mortality. Radiotherapy and chemotherapy remain the main treatments for unresectable, locally advanced esophageal cancer, but a relapse and drug resistance are still common. The optimized choice for therapeutic schemes with low toxicity and a high quality of life is unclear when local progression occurs after radiotherapy and chemotherapy. Fluoroscopy-guided photodynamic therapy (PDT) on patients with recurrent esophageal cancer in whom the endoscope cannot pass may be used as a salvage treatment, and nanoparticle albumin-bound paclitaxel (Nab-P) has been shown to be effective for advanced esophageal cancer. The combination of PDT and Nab-P might be an effective and tolerable option for advanced esophageal cancer. Case summary: The authors present a 65-year-old male patient diagnosed with esophageal squamous cell carcinoma (ESCC) confirmed to have developed local progression after receiving radiotherapy and chemotherapy. Severe esophageal stenosis, mild malnutrition and anemia, and radiation pneumonia were found when he was admitted to the authors' hospital. For rapid reduction of tumor burden and to restore normal diet, he received PDT by the X-ray fluoroscopy positioning method and Nab-P chemotherapy. The patient obtained clinical benefit from these treatments, and improved his quality of life. Conclusions: This case demonstrates potential advantages of fluoroscopy-guided PDT combined with Nab-P in reducing the tumor load, preserving organ function, and improving the quality of life, as well as the beneficial effect on locally advanced esophageal cancer after radiotherapy and chemotherapy. This combination therapy provides an alternative for the clinical treatment of locally advanced esophageal cancer and it has broad prospects in treatment of the disease. Core tip: Herein, the authors report a case of a patient with ESCC who suffered locally progressive disease after chemotherapy and radiotherapy as well as malnutrition and mild anemia because of feeding difficulties. The patient was treated with PDT, which was assisted by a new positioning technique of X-ray fluoroscopy and Nab-P chemotherapy, and finally achieved clinical benefits. In addition, a modified transnasal feeding tube was also applied in the process of fluoroscopy-guided PDT in this article.

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., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

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/m 2 , 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., (© 2022. The Author(s).)

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.

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., Competing Interests: Masahiro Morise reports personal fees and other from Taiho, grants and personal fees from Boehringer-ingelheim, personal fees from Daiichi Sankyo, grants and personal fees from Eli Lilly, personal fees and other from Chugai, personal fees and other from Astra Zeneca, personal fees and other from Ono, personal fees and other from Pfizer, personal fees and other from MSD, other from Merk serono, other from Kissei, other from Novartis, other from Roche, outside the submitted work. Yasuhiro Kondoh serves as a consultant to Asahi Kasei Pharma Corp., Shionogi & Co. Ltd., Boehringer Ingelheim Co., Ltd., Janssen Pharmaceutical K.K., Healios K.K., Chugai Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd., received lecture fees from Asahi Kasei Pharma Corp., Shionogi & Co. Ltd., and Boehringer Ingelheim Co., Ltd., Astra Zeneca K.K, Eisai Inc., KYORIN Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma, and Novartis Pharma K.K., outside the presentation work; the others have no conflict of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

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.

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2022. The Author(s).)

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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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)., (© 2021. The Author(s).)

Introduction: We aimed to evaluate the efficacy and safety of nanoparticle albumin-bound (nab-) paclitaxel for previously treated patients with advanced NSCLC., Methods: In this randomized, open-label, noninferiority phase 3 trial, we enrolled patients with advanced NSCLC previously treated with cytotoxic chemotherapy. Patients were randomly allocated (1:1) to receive docetaxel (60 mg/m 2 ) on day 1 or nab-paclitaxel (100 mg/m 2 ) on days 1, 8, and 15 of a 21-day cycle. The primary end point was overall survival (OS) analyzed on an intention-to-treat basis., Results: Between May 22, 2015, and March 12, 2018, a total of 503 patients were randomly allocated to the treatment. Median OS was 16.2 months (95% confidence interval [CI]: 14.4-19.0) for the 252 patients allocated to nab-paclitaxel and 13.6 months (95% CI: 10.9-16.5) for the 251 patients allocated to docetaxel (hazard ratio = 0.85, 95.2% CI: 0.68-1.07). Median progression-free survival was 4.2 months (95% CI: 3.9-5.0) for the nab-paclitaxel group versus 3.4 months (95% CI: 2.9-4.1) for the docetaxel group (hazard ratio = 0.76, 95% CI: 0.63-0.92, p = 0.0042). The objective response rate was 29.9% (95% CI: 24.0-36.2) for the nab-paclitaxel group and 15.4% (95% CI: 10.9-20.7) for the docetaxel group (p = 0.0002). Adverse events of grade greater than or equal to 3 included febrile neutropenia (5 of 245 patients [2%] in the nab-paclitaxel group versus 55 of 249 patients [22%] in the docetaxel group) and peripheral sensory neuropathy (24 [10%] versus 2 [1%], respectively)., Conclusions: Nab-paclitaxel was noninferior to docetaxel in terms of OS. It should, thus, be considered a standard treatment option for previously treated patients with advanced NSCLC., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

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., (© 2021. The Author(s).)

Combination chemotherapy with two or more complimentary drugs has been widely used for clinical cancer treatment. However, the efficacy and side effects of combination chemotherapy still remain a challenge. Here, we constructed an albumin-stabilized layered double hydroxide nanoparticle (BLDH) system to simultaneously load and deliver two widely used anti-tumor drugs, i.e. 5-fluorouracil (5FU) and albumin-bound PTX (Abraxane, ABX) for colorectal cancer treatment. The cellular uptake test has revealed that 5FU-ABX encapsulated BLDH (BLDH/5FU-ABX) nanoparticles were efficiently internalized by the colorectal cancer cell (HCT-116), synergistically inducing apoptosis of colon cancer cells. The in vivo test has demonstrated that BLDH/5FU-ABX nanomedicine significantly inhibited the tumor growth after three intravenous injections, without any detectable side effects. The enhanced therapeutic effectiveness is attributed to efficient accumulation of BLDH/5FU-ABX at tumor sites and acid-sensitive release of co-loaded drugs. Thus, combination chemotherapy based on BLDH/5FU-ABX nanomedicine would be a new strategy for colorectal cancer treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this article, we will describe the properties of albumin and its biological functions, types of sources that can be used to produce albumin nanoparticles, methods of producing albumin nanoparticles, its therapeutic applications and the importance of albumin nanoparticles in the production of pharmaceutical formulations. In view of the increasing use of Abraxane and its approval for use in the treatment of several types of cancer and during the final stages of clinical trials for other cancers, to evaluate it and compare its effectiveness with conventional non formulations of chemotherapy Paclitaxel is paid. In this article, we will examine the role and importance of animal proteins in Nano medicine and the various benefits of these biomolecules for the preparation of drug delivery carriers and the characteristics of plant protein Nano carriers and protein Nano cages and their potentials in diagnosis and treatment. Finally, the advantages and disadvantages of protein nanoparticles are mentioned, as well as the methods of production of albumin nanoparticles, its therapeutic applications and the importance of albumin nanoparticles in the production of pharmaceutical formulations.

We developed a novel preparative method for nanoparticle albumin-bound (nab) paclitaxel with high drug loading, which was based on improved paclitaxel solubility in polyethylene glycol (PEG) and self-assembly of paclitaxel in PEG with albumin powders into nanoparticles. That is, paclitaxel and PEG were firstly dissolved in ethanol, which was subsequently evaporated under vacuum. The obtained liquid was then mixed with human serum albumin powders. Thereafter, the mixtures were added into phosphate-buffered saline and nab paclitaxel suspensions emerged after ultrasound. Nab paclitaxel was finally acquired after dialysis and freeze drying. The drug loading of about 15% (W/V) were realized in self-made nab paclitaxel, which was increased by approximately 50% compared to 10% (W/V) in Abraxane. Now this new preparative method has been authorized to obtain patent from China and Japan. The similar characteristics of self-made nab paclitaxel compared to Abraxane were observed in morphology, encapsulation efficiency, in vitro release, X-ray diffraction analysis, differential scanning calorimetry analysis, and circular dichroism spectra analysis. Consistent concentration-time curves in rats, biodistributions in mice, anti-tumor activities in mice, and histological transmutation in mice were also found between Abraxane and self-made nanoparticles. In a word, our novel preparative method for nab paclitaxel can significantly improve drug loading, obviously decrease product cost, and is considered to have potent practical value., Competing Interests: The technology described in this manuscript forms the basis of patents granted by the China National Intellectual Property Administration (patent number:201810164476.7) and Japan Patent Office (patent number: 6738500). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

As the nanoparticle albumin-bound paclitaxel (nab-PTX) is free of ethanol and premedication, the duration of administration is shorter and patients can drive themselves to and from the hospital. In the 2018 Japanese gastric cancer treatment guidelines, ramucirumab (RAM) plus weekly nab-PTX is conditionally recommended for previously treated patients with advanced gastric cancer. Here, we retrospectively analysed the efficacy and safety of RAM+nab-PTX for such patients in community hospitals. From January 2018 to December 2019, 43 patients with metastatic and recurrent gastric cancer received RAM+nab-PTX treatment. Six patients (13.9%) were older than 80 years and 9 patients (20.9%) showed ECOG-PS 2. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR), and adverse events (AEs) were reviewed retrospectively. Median PFS was 114 days (95% confidence interval [CI]: 84-190) and median OS was 297 days (95% CI: 180-398). ORR and DCR were 32.4% and 72.2%, respectively. The incidence rates of ≥grade 3 neutropenia and febrile neutropenia were 53.5% and 2.3%, respectively. No treatment-related deaths occurred. RAM plus nab-PTX combination therapy demonstrated manageable toxicity even patients who were elderly or had an ECOG-PS 2. This treatment is useful in community hospital settings., Competing Interests: No potential conflict of interest relevant to this article was reported.

Aim: To compare the efficacy and safety of 2-weekly nanoparticle albumin-bound paclitaxel (nP) and 3-weekly docetaxel regimens as neoadjuvant systemic therapy (NST) for breast cancer. Materials & methods: Patients (n = 201) received NST comprising either dose-dense epirubicin and cyclophosphamide followed by 2-weekly nP (n = 104) or 3-weekly courses of epirubicin and cyclophosphamide followed by docetaxel (n = 97). Results: Higher pathological complete response rates were achieved by the nP group. Subgroup analysis showed that the nP-based regimen achieved higher pathological complete response rates in patients with triple-negative tumor cells and high Ki67 levels. However, grades 3-4 peripheral sensory neuropathies were more frequent in the nP group. Conclusion: The 2-weekly nP-based regimen might be a better choice of NST for patients with breast cancer.